Life Under the Microscope

Metastatic carcinoma from the bladder

2008-08-08T21:52:00.006+08:00

Answer:
Metastatic carcinoma from the bladder

Exposition:

Criteria for diagnosis clinically: Violaceous papules, but mostly plaques of shapes bizarre, they being geometric and largely polycyclic, are changes that in this instance are those of metastases from carcinoma of the bladder.

Differential diagnosis clinically: The attributes clinical are so unusual that no differential diagnosis meaningful can be generated.

Criteria for diagnosis histopathologically: Neoplastic cells with large, pleomorphic, hyperchromatic nuclei and discernible pink cytoplasm are present within widely dilated lymphatics and in the interstitium in the upper part of the dermis, those being changes of metastatic carcinoma that in this patient came from a primary in the bladder.

Differential diagnosis histopathologically: That this is a metastasis cannot be challenged, but the precise nature of the primary carcinoma cannot be inferred from the findings alone in this section of skin.

Clinicopathologic correlation: The lesions are elevated because of the infiltrates of neoplastic cells; they are purplish because, in vivo, venules in the upper half of the dermis are dilated markedly and their lumen is replete with erythrocytes, which also are extravasated in the reticular dermis; and the surface of the lesion is smooth because the cornified layer is normal.

Options for therapy predicated on knowledge of histopathologic findings: Sad to say, a patient with metastatic disease such as this has a poor prognosis, irrespective of what therapy is attempted.

Lessons:

(1) The features clinical in this patient are so extraordinary that considerations diagnostic cannot be conventional. Unless one has had experience with another patient whose lesions were very similar to these and that proved to contain metastases, it would be impossible to come to a diagnosis clinical with certainty here.

(2) It is easy in this section of tissue to make a diagnosis of carcinoma metastatic to skin because lymphatics are stuffed with cells of the carcinoma, that being proof positive of metastasis.

(3) Although in this particular instance it is impossible to determine the site of the primary carcinoma, that is not the case always in regard to metastases to skin. For example, it is possible, with confidence, to diagnose many an example of metastatic thyroid carcinoma, metastatic breast carcinoma, metastatic stomach carcinoma, metastatic renal-cell carcinoma, and metastatic melanoma to skin. The attributes cytopathologic of the metastasis are just like those of the primary.

(4) The presentations clinical of metastases to skin are as protean as are the appearances histopathologic, ranging from a solitary papule to countless nodules. In this patient, all of the lesions are purplish plaques. The variations are numerous.

(5) Although any site anatomic of skin can be visited by malignant neoplastic cells of a metastasis, the scalp is a favorite for many a type of carcinoma. Not uncommonly, melanoma metastasizes to skin. Sadly, it often has predilection for the brain.

(Source: Derm101)

19 year-old male with hypertension and renal insufficiency

2008-08-08T21:02:00.019+08:00

Clinical History

A 19 year-old Hispanic man presented with hypertension and renal insufficiency (serum creatinine of 7.1 mg/dl). The peripheral blood smear showed pancytopenia but no circulating blasts.

A CT scan demonstrated bilateral renal enlargement with lymphadenopathy in the retroperitoneum and neck.

A core biopsy was obtained.

Immunostains were performed.

CD10

CD34

CD79a

TdT

Diagnosis:

Pre-B acute lymphoblastic lymphoma involving the kidneys

Discussion:

A bone marrow biopsy was also obtained which showed a diffuse infiltration by tumor cells with a similar morphology as the renal biopsy.

The renal biopsy showed a diffuse infiltrate of monotonous blastoid cells obliterating the normal renal architecture. The bone marrow biopsy showed a similar population of cells replacing most of the marrow. Immunophenotyping by flow cytometry and immunohistochemistry showed that the tumor cells co-express CD19, CD20, CD10, CD34, CD38, CD79a, HLA-DR and TdT.

Precursor B-cell acute lymphoblastic leukemia/lymphoma (ALL) is a common pediatric hematologic malignancy. Although renal failure due to tumor lysis is a recognized complication of treatment, initial presentation with renal failure is distinctly uncommon. ALL must be considered among the causes of acute renal failure when the kidneys are enlarged. Careful morphologic study and immunophenotyping by flow cytometry or immunohistochemistry is helpful to arrive at the correct diagnosis, and to avoid confusion with other small blue cell tumors which may involve the kidney, such as Wilm’s tumor (J Pediatr Hematol Oncol 2008;30:471), small cell carcinoma or Ewing’s sarcoma/primitive neuroectodermal tumor.

Bilateral nephromegaly simulating wilms tumor: a rare initial manifestation of acute lymphoblastic leukemia.
Pradeep R, Madhumathi DS, Lakshmidevi V, Premalata CS, Appaji L, Patil SA, Swapnil B.
A 7-year-old boy was referred with a provisional diagnosis of bilateral Wilms tumor. Peripheral smear revealed elevated leukocyte count with 90% blasts. Bone marrow aspiration and biopsy were hypercellular with sheets of blasts. Immunohistochemistry on paraffin sections showed a pre-B phenotype of acute lymphoblastic leukemia. Computerized tomographic scan of the abdomen showed moderate bilateral renal enlargement. Ultrasound-guided fine needle aspiration cytology of both kidneys showed blasts similar to those seen in the bone marrow. Finally, a diagnosis of pre-B acute lymphoblastic leukemia infiltrating both the kidneys was made. This case is being presented because of its rarity.

Additional references:

1. Weinstein Howard J, Tarbell Nancy J. Leukemias and lymphomas of childhood. Cancer Principles and Practice of Oncology. 5th edition; Ch.44: Section 2, 2145-65

2. Boueva A, Bouvier R. Precursor B-cell lymphoblastic leukemia as a cause of a bilateral nephromegaly. Pediatr Nephrol 2005;20:679

Precursor B-cell lymphoblastic leukemia as a cause of a bilateral nephromegaly.
Boueva A, Bouvier R.
Nephromegaly and non-oliguric acute renal failure is an unusual manifestation of lymphoblastic infiltration of the kidneys. We report the clinical history of a female child where a precursor B-cell lymphoblastic proliferation was diagnosed at the age of 21 months by a surgical renal biopsy for an unexplained bilateral nephromegaly. Lymphoblastic infiltration should be suspected in any patient presenting with unexplained renal failure and enlarged kidneys. The importance of renal biopsy to identify the etiology of renal failure and nephromegaly is emphasized.

3. Mehta A, Gulati K, Jain M, Gulati S. Non-Hodgkin lymphoma in a child presenting as nephromegaly and acute renal failure. Indian Pediatr 2001;38:407

4. Gilboa N, Lum GM, Urizar RE. Early renal involvement in acute lymphoblastic leukemia and non-Hodgkin lymphoma in children. J Urol 1983;129:364

Early renal involvement in acute lymphoblastic leukemia and nonHodgkin's lymphoma in children.
Gilboa N, Lum GM, Urizar RE.
Clinical manifestations of kidney disease, particularly renal failure, caused by malignant infiltration in patients with acute lymphoblastic leukemia or nonHodgkin's lymphoma have been described rarely. We report 1 case of acute lymphoblastic leukemia and 3 cases of nonHodgkin's lymphoma in which renal disease was the only or one of the presenting manifestations of malignancy. Of these patients 2 had rapidly progressive renal failure with nephromegaly, 1 presented with bilateral abdominal masses caused by severe nephromegaly and with microscopic hematuria, and 1 had microscopic hematuria without nephromegaly. In all 4 patients kidney biopsy revealed malignant infiltration. In the 2 patients who presented with renal failure kidney function promptly returned to normal after chemotherapy and irradiation of the kidneys. Prompt and correct diagnosis of nephropathy, when it is the only or one of the presenting signs of acute lymphoblastic leukemia or nonHodgkin's lymphoma, is necessary to expedite initiation of specific antitumor therapy.

5. Nizze H et al. Primary renal manifestations in malignant lymphomas and leukemia. Pathologe 2003;24:460

[Primary renal manifestation in malignant lymphomas and leukemia]
Nizze H, Prall F, Wigger M, Eggers G, Knieling K, Parwaresch R.
Primary manifestation of malignant lymphoma and/or leukaemia rarely occurs in the kidney. It can be the cause of a hitherto unexplained acute renal failure or it is incidentally detected as shown in the three cases under report.1.A 68-year-old man was operated on because of a symptomatic tumour in his right kidney. At nephrectomy, a conventional (clear cell) renal cell carcinoma was found simultaneously with an occult mantle cell lymphoma infiltrating the adjacent renal and extrarenal tissue. Clinical follow-up uncovered nodal and bone marrow involvement, so that a primary renal manifestation of mantle cell lymphoma was apparent.2.A 69-year-old man with suspected vertebral metastasis underwent partial renal resection because of a mass in his left kidney. Histologically and immunohistochemically, the renal infiltration was diagnosed as a precursor B-lymphoblastic lymphoma. After chemotherapy and irradiation, leukaemic blood cell counts with 50% lymphoblasts proved a primary renal manifestation of precursor B-lymphoblastic leukaemia/lymphoma.3.A 13-year-old boy presented clinically with renal failure, enlarged kidneys, and normal urinalysis. Renal biopsy showed a diffuse interstitial infiltration with atypical T-lymphoblasts compressing tubules and surrounding preserved glomeruli. Subsequent clinical bone marrow smears presented 60% T-lymphoblasts, so that the final diagnosis of a primary renal manifestation of acute T-lymphoblastic leukaemia of mature thymic cortex type was made. Immediate chemotherapy resulted in total recovery of renal function and bone marrow findings.

6. John William J, Foon Kenneth A, Patchell Roy A. Paraneoplastic syndromes Cancer Principles and Practice of Oncology. Vol.2; Ch.46: 2397-422.

7. PathologyOutlines.com - Leukemia, Acute chapter

(Source: Pathology Outlines by Dr. Nat Pernick)

Pruritic plaque with pustules on the nose and cheeks

2008-08-03T21:26:00.014+08:00

The patient
A 16-year-old female presented herself to us with a 2-month history of pruritic, erythematous, annular plaques studded with papules and pustules on her face, particularly on the malar and nasal areas (Fig. 1). The lesions were enlarged by peripheral extension and central clearing was noted. The patient had been diagnosed previously with seborrheic dermatitis and was treated with topical steroids and antifungals with minimal improvement.

Cutaneous examination revealed an asymmetric, well-circumscribed, erythematous, and edematous plaque on the nasal area and both cheeks with central clearing and overlying fine scales. Scattered pustules and papules were noted on the surface of the plaque.

Fig. 1: Erythematous, edematous plaque on the nasal area and both cheeks with overlying fine scales and scattered pustules and papules.

Histopathology
A 4 mm punch biopsy was taken from the periphery of the lesion (Figs. 2A–K). What is your diagnosis?

Figs. 2A – K: Histopathology.

Answer
Ofuji's disease (eosinophilic pustular folliculitis)

Histopathologic examination of a biopsy specimen taken from the periphery of the lesion showed focal parakeratosis of the stratum corneum. There was spongiosis of the epidermis with exocytosis of eosinophils. The dermis revealed a moderately dense perivascular and periadnexal inflammatory infiltration consisting of lymphocytes, numerous eosinophils, and some neutrophils. There was spongiosis of the follicular epithelium and telangiectasia of surrounding blood vessels. Noteworthy was the prominent eosinophilic infiltration of the seboglandular ducts and sebaceous glands in which eosinophilic abscesses were observed. Periodic acid-Schiff staining for fungus was negative.

Laboratory examination showed normal results of complete blood count, urinalysis, hepatic and renal function tests, serum glucose, erythrocyte sedimentation rate, and antinuclear antibody titer. Culture from pustules showed no bacterial growth. A potassium hydroxide (KOH) smear was negative for spores and hyphae, and there was no growth observed on fungal culture.
These findings together enabled a diagnosis of Ofuji's disease to be made.

Comment
The classic form of eosinophilic pustular folliculitis (Ofuji's disease) was initially described among the Japanese and Chinese as a rare dermatosis characterized by recurrent outbreaks of pruritic, sterile, papulopustular skin lesions with tendency to form circinate plaques.[1 ] The lesions have a tendency to extend peripherally with central clearing and resolve with postinflammatory hyperpigmentation. The seborrheic areas are the most frequently affected sites although the extremities, mucous membranes, and palms and soles may be involved. [1–4 ] The face is affected in 95% of cases and is often the first site of involvement. [5,6 ] Peripheral eosinophilia is observed in 50% of cases but normalizes once the skin lesions resolve. [6 ] The etiology of eosinophilic pustular folliculitis remains unknown. Various immunological dysfunctions have been reported in some patients, but this is not a consistent feature. [7 ]

Eosinophilic pustular folliculitis associated with HIV infection has been regarded by some authors as a separate clinical entity as it usually presents as intensely pruritic, erythematous, urticarial papules, which are located predominantly on the trunk. [8 ]

Eosinophilic pustular folliculitis has also been described in association with non-Hodgkin's lymphoma, Hodgkin's lymphoma, leukemia, myelodysplastic syndrome, and bone marrow transplantation, in which the clinical presentations were identical to those seen in HIV patients. [9–13 ]

Eosinophilic pustular folliculitis in infancy has also been observed but also seems to be a different clinical variant because of constant and predominant involvement of the scalp. [14,15 ] Some authors have called into question whether this latter condition really represents a distinctive disease or whether patients diagnosed with it suffer from other diseases such as scabies and arthropod reactions. [16 ]

Drug-induced eosinophilic pustular folliculitis has been documented with allopurinol, timepidium bromide, minocycline, indeloxazine hydrochloride, and carbamazepine. [5,17–19 ]

The histologic pattern of eosinophilic pustular folliculitis is characterized by a combination of a perivascular and interstitial eosinophil-rich infiltrate and an eosinophilic-rich pustular infundubulitis. The follicular infundibulum and outer root sheaths usually show intracellular and intercellular edema. The majority of the hair follicles are preserved but some show disruption or destruction of the wall by the inflammatory infiltrate. [20 ] Eosinophils are found within hair follicles in 95% of cases, in the sebaceous glands (65%), around sweat glands (80%), and in between collagen fibers (100%). The formation of abscesses in the follicles, sebaceous glands, or both is seen in 40% of cases. [6 ] In addition to eosinophils, there are variable numbers of neutrophils and some mononuclear cells. [21 ] Alcian blue stain reveals accumulation of acid mucopolysaccharides in spongiotic lesions of follicles or sebaceous glands (35%). Nissl modified staining reveals moderate increase in the number of tryptase-positive and chymase-negative mast cells surrounding follicles and sebaceous glands (100%). [6 ]

Because lesions of eosinophilic pustular folliculitis most often arise in seborrheic areas, some authors believe that a relationship exists between sebaceous gland activity and the development of papules and plaques. Fresh surface skin lipids from seborrheic areas in normal adults and lesional stratum corneum extracts from pustules of patients with EPF contain chemotactic substances for eosinophils and polymorphonuclear leukocytes (PMNs). [22 ] However, mechanisms that trigger the activation of follicular keratinocytes or the sebaceous glands to release cytokines, chemotactic factors, and intercellular adhesions molecule-1 are still poorly understood. Aside from eosinophils, the cells surrounding the sebaceous glands consist of T-helper lymphocytes, Langerhans' cells and macrophages. An increased number of mast cells has been described around hair follicles and sebaceous glands suggesting a role for these cells in the pathogenesis of the disease. [6 ] Within the sebaceous glands, markers of sebaceous gland differentiation (HMF 61, HMF 62, and OM-1) are markedly reduced while they were normally expressed in the hair follicles. Similarly, markers for acute inflammatory activation of the epithelia (ICAM-1 and MAC 387) were strongly expressed in the sebaceous glands while they were normal in the follicles. The relative propensity of the infiltrate towards the sebaceous glands rather than the hair follicles is clearly demonstrated in our case and has been observed by some authors. [5 ]

Various treatments have been tried for eosinophilic pustular folliculitis but no definite effective therapy has been established. Although systemic corticosteroids are the most commonly used first-line treatment, favorable effects have been observed with Indomethacin and Isotretinoin. The efficacy of oral or topical indomethacin may be secondary to the inhibition of cyclooxygenase, which in turn decreases the production of arachidonic acid-derived eosinophilic chemotactic factors, lipid chemotactic factor, 12-L-hydroxy-5,8,10-heptadecatrienoic acid, and prostaglandins.[6 ] On the other hand, Isotretinoin exerts anti-inflammatory action on PMNs, reduces chemotactic activity, and decreases the local synthesis of arachidonic acid-derived eosinophilic cationic factor. This is recommended as first-line treatment when histology shows primary involvement of the seboglandular units.[5 ]

The patient presented here was treated with oral Prednisone at 0.75 mg/kg/day on tapering doses for 8 weeks. There was noted immediate clearing of facial lesions upon initiation of treatment. The patient is now being given oral Indomethacin at 50 mg/day to control flares and remissions.

Summary

Background: Ofuji's disease or the "classic" eosinophilic pustular folliculitis is a rare dermatosis characterized by intermittent outbreaks of plaques with pustules mainly located in seborrheic areas. The histologic features show accumulation of eosinophils, neutrophils and lymphocytes around the pilosebaceous unit with some degree of spongiosis, and destruction of follicles.

Objectives: To demonstrate the clinical and histopathologic characteristics of a classic case of Ofuji's disease.

Patients/Methods: Examination revealed well-circumscribed erythematous, edematous plaques with overlying pustules and central clearing over the nose and malar area and histopathologic findings of a moderately dense perivascular and periadnexal inflammatory infiltration consisting of lymphocytes, numerous eosinophils, and some neutrophils. The sebaceous lobules and ducts are primarily affected with formation of eosinophilic abscesses within glands. Systemic corticosteroids are considered the treatment of choice in severe flares and are usually given in short courses. Indomethacin and Isotretinoin are excellent alternative treatments.

Conclusion: Recognition of the clinical and histopathologic presentation of a classic case of Ofuji's disease is important for immediate diagnosis and successful treatment despite its clinical course of flares and remissions.

References
1. Ofuji S, Ogino A, Horio T, et al. Eosinophilic pustular folliculitis. Acta Derm Venereol. 1970;50:195–203.
2. Takematsu H, Nakamura K, Igarashi M, Tagami H. Eosinophilic pustular folliculitis: report of two cases with a review of the Japanese literature. Arch Dermatol. 1985;121:917–920.
3. Colton AS, Schachner L, Kowalczyk AP. Eosinophilic pustular folliculitis. J Am Acad Dermatol. 1986;14:469–474.
4. Cutler TP. Eosinophilic pustular folliculitis. Clin Exp Dermatol. 1981;6:327–332.
5. Blume-Peytavi U, Chen W, Djemadji N et al. Eosinophilic pustular folliculitis (Ofugi's disease). J Am Acad Dermatol. 1997;37:259–262.
6. Ishiguro N, Shishido E, Okamoto R, et al. Ofugi's disease: a report on 20 patients with clinical and histopathologic analysis. J Am Acad Dermatol. 2002;46:827–833.
7. Magro CMJ, Crowson AN. Eosinophilic pustular follicular reaction: a paradigm of immune dysregulation. Int J Dermatol. 1994;33:172–178.
8. Rosenthal D, Le Boit PE, Klumpp L, Berger TG. Human immunodeficiency virus-associated eosinophilic folliculitis: a unique dermatosis associated with advanced human immunodeficiency virus infection. Arch Dermatol. 1991;127:206–209.
9. Patrizi A, Di Lerna V, Neri I, Gherlinzoni F. Eosinophilic pustular folliculitis (Ofugi's disease) and non-Hodgkin lymphoma. Acta Derma Venereol. (Stockh) 1992;72:146–147.
10. Bull RH, Harland CA, Fallowfield ME, Mortimer PS. Eosinophilic folliculitis: a self-limiting illness in patients being treated for haematological malignancy. Br J Dermatol. 1993;129:178–182.
11. Lambert J, Berneman Z, Dockx P, Stenvens W, Van Marck E. Eosinophilic pustular folliculitis and B-cell chronic lymphatic leukaemia. Dermatology. 1994;73:2512–2514.
12. Evans TR, Mansi JL, Bull R, Fallowfield ME, Bevan DH, Harmer CL, et al. Eosinophilic folliculitis occurring after bone marrow autograft in a patient with non-Hodgkin's lymphoma. Cancer. 1994;73:2512–2514.
13. Jang KA, Chung ST, Choid JH, Sung KJ, Moon KC, Koh JK, Eosinophilic pustular folliculitis (Ofugi's disease) in myelodysplastic syndrome. J Dermatol. 1998;25:742–746.
14. Lucky AW, Esterly NB, Heskel N, et al. Eosinophilic pustular folliculitis in infancy. Pediatr Dermatol. 1984;1:202–206.
15. Duarte AM, Kramer J, Yusk JW, et al. Eosinophilic pustular folliculitis in infancy and childhood. Am J Dis Child. 1993;147:197–200.
16. Ziemer M, Böer A. Eosinophilic pustular folliculitis in infancy: not a distinctive inflammatory disease of the skin. Am J Dermatopathol. 2005;27(5):443–455.
17. Maejima H., Mukai H, Hikaru E. Eosinophilic pustular folliculitis induced by allopurinol and timepidium bromide. Acta Derm Venereol. 2002;82:316–317.
18. Andreano JM, Kantor GR, Bergfeld WF, Tuthill RJ, Taylor JS. Eosinophilic cellulitis and eosinophilic pustular folliculitis. J Am Acad Dermatol. 1989;20:934–936.
19. Kimura K, Ezoe K, Yokozeki H, Katayama I, Nishioka K. A case of pustular folliculitis (Ofugi's disease) induced by patch and challenge text with indeloxazine hydrochloride. J Dermatol. 1996;23:479–483.
20. Jaliman HD, Phelps RG, Fleishchmajer R. Eosinophilic pustular folliculitis. J Am Acad Dermatol. 1986;14:479–482.
21. Mc Calmont TH, Altemus D, Maurer T, Berger TG. Eosinophilic folliculitis: the histologic spectrum. Am J Dermatopathol. 1995;17:439–466.
22. Takematsu H, Tagami H. Eosinophilic pustular folliculitis: studies on possible chemotactic factors involved in the formation of pustules. Br J Dermatol. 1986;114: 209–215.

(Source: Dermatopathology: Practical & Conceptual July - September 2008 Volume 14, #3)

50 y/o male with duodenal polyp

2008-07-14T15:18:00.012+08:00

Clinical History:

A 50 year old man presented with an 8 cm duodenal polyp. Five years ago, he complained of gastric pain and blood in his stool. At endoscopy, he had a 5 cm duodenal polyp, diagnosed as "benign". However, removal of the polyp was delayed for years because a CT scan found a renal cell carcinoma, which was excised. At his recent surgery for the duodenal polyp, a “wet” villous mass was found that abutted the Ampulla of Vater.

Gross:

Microscopic:

Diagnosis:

Hyperplastic polyp of gastric metaplasia / gastric heterotopia

Discussion:

This case demonstrates the presence of mature gastric tissue in the duodenum. Heterotopia is a developmental anomaly, defined as the presence of mature tissue in a location where it is not normally found. Gastric heterotopia has been described in the esophagus (inlet patch), duodenum, gallbladder, Meckel’s diverticulum, and other sites in the bowel. It is associated with diarrhea, obstruction, dyspepsia, ulceration and GI bleeding (Pediatr Dev Pathol 2000;3:277).

Extensive gastric heterotopia of the small intestine resulting in massive gastrointestinal bleeding, bowel perforation, and death: report of a case and review of the literature.

Lambert MP, Heller DS, Bethel C.

Gastric heterotopia of the small intestine is a rare occurrence outside of Meckel's diverticulum and intestinal duplication. The vast majority of cases of gastric heterotopia occur as polypoid or tumorous lesions in the duodenum. These lesions have been associated with clinical symptoms including diarrhea, obstruction, dyspepsia, ulceration, and gastrointestinal bleeding. We present a case of gastric heterotopia that is unique because the lesions occurred as multiple, carpet-like, nonpolypoid areas throughout a large portion of the small intestine. A review of the literature is included.

Grossly, heterotopia usually presents as one or more nodules or sessile polyps. Microscopically, it consists of fundic type mucosa with chief and parietal cells, lined by foveolar epithelium, with a full mucosal thickness, forming a mucosal island. It is rarely associated with gastric type adenomas (Virchows Arch 1999;435:452).

'Pyloric gland-type adenoma' arising in heterotopic gastric mucosa of the duodenum, with dysplastic progression of the gastric type.

Kushima R, Rüthlein HJ, Stolte M, Bamba M, Hattori T, Borchard F.

'Pyloric gland-type adenoma' is a recently described and very rare entity. We report a case of a pedunculated polyp of the duodenal bulb showing the features of pyloric gland-type adenoma. Heterotopic gastric mucosa was found adjacent to the tumour. Immunohistochemically, the tumour cells at the surface of the polyp showed foveolar-type mucin (M1) while most other tumour cells showed deep gastric mucin (M2), displaying a pattern of differentiation similar to the normal gastric mucosa. The polyp also showed villous or papillary structures with disorganization of gastric differentiation and marked increase of proliferating in foci cells. This is the first case of pyloric gland-type adenoma found to arise in heterotopic gastric mucosa of the duodenum, showing dysplastic progression of the gastric type.

Heterotopia differs from metaplasia. Metaplasia is the change from one type of fully differentiated tissue to another fully differentiated tissue, usually due to chronic inflammation. The lower esophagus and duodenal bulb are common sites of gastric metaplasia, which may occur as a protective response to gastric acid. Gastric metaplasia only occupies part of the mucosal thickness, and intermingles with native tissue. It typically is microscopic, and does not present with any gross findings. Histologically, it lacks the specialized cells of fundic type mucosa. It may be important to distinguish gastric metaplasia from heterotopia, because metaplasia is associated with duodenitis and often H. pylori, which may require treatment (Braz J Med Biol Res 2007;40:897, Dig Liver Dis 2002;34:16).

Duodenal gastric metaplasia and Helicobacter pylori infection in patients with diffuse nodular duodenitis.

Li XB, Ge ZZ, Chen XY, Liu WZ

Whether the regression of gastric metaplasia in the duodenum can be achieved after eradication of Helicobacter pylori is not clear. The aim of the present study was to investigate the relationship between H. pylori infection and gastric metaplasia in patients with endoscopic diffuse nodular duodenitis. Eighty-six patients with endoscopically confirmed nodular duodenitis and 40 control patients with normal duodenal appearance were investigated. The H. pylori-positive patients with duodenitis received anti-H. pylori triple therapy (20 mg omeprazole plus 250 mg clarithromycin and 400 mg metronidazole, all twice daily) for one week. A control endoscopy was performed 6 months after H. pylori treatment. The H. pylori-negative patients with duodenitis received 20 mg omeprazole once daily for 6 months and a control endoscopy was performed 2 weeks after treatment. The prevalence of H. pylori infection was 58.1%, and the prevalence of gastric metaplasia was 57.0%. Seventy-six patients underwent endoscopy again. No influence on the endoscopic appearance of nodular duodenitis was found after eradication of H. pylori or acid suppression therapy. However, gastric metaplasia significantly decreased and complete regression was achieved in 15/28 patients (53.6%) 6 months after eradication of H. pylori, accompanied by significant improvement of other histological alterations. Only mild chronic inflammation, but not gastric metaplasia, was found in the control group, none with H. pylori infection in the duodenal bulb. Therefore, H. pylori infection is related to the extent of gastric metaplasia in the duodenum, but not to the presence of diffuse nodular duodenitis.

Regression of duodenal gastric metaplasia in Helicobacter pylori positive patients with duodenal ulcer disease.

Ciancio G, Nuti M, Orsini B, Iovi F, Ortolani M, Palomba A, Amorosi A, Surrenti E, Ilani SM, Surrenti C.

BACKGROUND: It is unclear whether the extent of duodenal gastric metaplasia is due to Helicobacter pylori and/or acid. AIMS: To investigate the role of Helicobacter pylori eradication in the regression of duodenal gastric metaplasia in patients with duodenal ulcer maintained in acid suppression conditions. METHODS:. Duodenal (anterior, superior inferior walls of first part of duodenum) and gastric antrum biopsies were obtained from 44 Helicobacter pylori positive duodenal ulcer patients. Helicobacter pylori infection was diagnosed by rapid urease test, histology and 13C-Urea Breath Test. Patients were treated with 20 mg omeprazole tid associated with 250 mg clarithromycin and 500 mg amoxycillin four times daily for 10 days and maintained with 20 mg omeprazole daily for 18 weeks. Control endoscopies were performed at 6 and 18 weeks after beginning treatment. RESULTS: Duodenal gastric metaplasia regression was observed in all (32/32) patients in whom Helicobacter pylori was eradicated, but in only 3 out of 6 patients in whom eradication was not achieved (p<0.>)

(Source: Pathology Outlines Case# 124 by Dr. Nat Pernick)

Derm101 Case: Basal Cell Carcinoma, Nodular

2008-07-12T23:36:00.003+08:00

Exposition

Criteria for diagnosis clinically: A pink papule with a hint of a violaceous cast, whose mostly shiny, smooth surface is traversed by telangiectases and whose border is scalloped subtly, represents a nodular type of basal-cell carcinoma.

Differential diagnosis clinically: There is none.

Criteria for diagnosis histopathologically: An asymmetrical neoplasm made up of abnormal trichoblasts organized in aggregations, some of which are separated by clefts from the adjacent altered stroma and are affiliated with necrosis of individual neoplastic cells joined by large zones in the center of aggregations that contain mucin in quantity, are findings that compute to a diagnosis of basal-cell carcinoma of the nodular type.

Differential diagnosis histopathologically: There is none.

Clinicopathologic correlation: The papule consists largely of aggregations of neoplastic cells; the reddish hue and the telangiectases are the result of capillaries and venules in the uppermost part of the dermis having been dilated widely in vivo and there stuffed with erythrocytes; and the shiny, smooth part of the surface is accounted for by compact orthokeratosis, whereas the scaly part is a manifestation of parakeratosis.

Options for therapy predicated on knowledge of histopathologic findings: A carcinoma such as this one must be removed in its entirety and although the neoplasm does extend to near one lateral margin, it seems, nonetheless, to have been extirpated. That being the case, it is still important to follow this patient at six-month intervals for one year to ensure that the basal-cell carcinoma does not persist at the local site.

Lessons

(1) The neoplasm shown here fulfills criteria, clinical and histopathologic, for diagnosis of nodular basal-cell carcinoma. Note how thin is the surface epidermis, an indication that likely it will not be long before evidences of erosion and, eventually, ulceration, became apparent.

(2) Signs of necrosis of individual neoplastic trichoblasts here are pyknosis and karyorrhexis. The cystic zones do not, however, consist of a mass of necrotic neoplastic cells, but rather of mucin, which appears as finely granular, lightly basophilic material. Neoplastic cells of basal-cell carcinoma have potential to manufacture acid mucopolysaccharides, and that capability is demonstrated well in this neoplasm.

(3) All epithelial cells in skin have capability to produce mucin. In normal skin that property is expected of apocrine glandular epithelium. In states pathologic, such as epithelial ("follicular") mucinosis, mucin is made by infundibular epithelium, sebaceous glandular epithelium, and follicular epithelium. Fibrocytes, possibly in conjunction with mast cells, also have capability to manufacture mucin, it being present normally in the papillary-periadnexal dermis and, to a much lesser extent, in the reticular dermis. Copious amounts of mucin appear in focal mucinosis, myxedema, and pretibial myxedema, in much less quantity in lichen myxedematosis, and somewhere in between in lupus erythematosus and dermatomyositis. The character chemically of "connective tissue mucin" is different from that of "epithelial mucin."

(4) Both benign and malignant epithelial neoplasms in skin may be associated with production of mucin. A dramatic example of that in a benign neoplasm is "eccrine mixed tumor" in which tiny donut-shaped aggregations of eccrine epithelial cells are embedded in lakes of mucin. Sometimes an apocrine hidradenoma is peppered by goblet cells whose cytoplasm houses plentiful mucin. Carcinomas of different types, in addition to basal-cell carcinoma, also may be affiliated with mucin, among those being keratoacanthomatous squamous-cell carcinoma and, in caricature, mucinous carcinoma (it being the analogue of colloid carcinoma of the breast and showing apocrine glandular differentiation). In theory, constituent neoplastic cells of any carcinoma of the skin have capability to make mucin.

(5) Both necrosis of neoplastic cells and production of mucin can occur together in basal-cell carcinoma, as is the situation here, or they can occur independent of one another.

(Source: Derm101)

Intermethod Differences in Results for Total PSA, Free PSA, and Percentage of Free PSA

2008-07-04T05:56:00.008+08:00

Abstract
Serum prostate-specific antigen (PSA) assays differ in calibration and response to different PSA forms. We examined intermethod differences in total PSA (tPSA) and free PSA (fPSA) measurements. We tested 157 samples with tPSA concentrations of 2 to 10 ng/mL (2-10 µg/L) using 6 PSA/fPSA method pairs and 1 tPSA method: ADVIA Centaur (complexed and total; Siemens Diagnostics, Tarrytown, NY), ARCHITECT i2000SR (Abbott Diagnostics, Abbott Park, IL), AxSYM (Abbott Diagnostics), IMMULITE 2000 (Siemens Diagnostics), Modular E170 (Roche Diagnostics, Indianapolis, IN), UniCel DxI 800 (Beckman Coulter, Brea, CA), and VITROS ECi (tPSA only; Ortho-Clinical Diagnostics, Raritan, NJ). Regression analysis was performed for PSA, fPSA, and percentage of fPSA with the ARCHITECT i2000SR comparison method. Differences between test and comparison methods were estimated at 2.5, 4.0, and 10.0 ng/mL (2.5, 4.0, and 10.0 µg/L) for tPSA and 15%, 20%, and 25% for percentage of fPSA. Relative differences were more than 10% at 4.0 ng/mL (4.0 µg/L) tPSA for the Centaur, IMMULITE, ECi, and DxI methods. At 20% fPSA, the relative difference was more than 10% for all methods except the AxSYM. Additional harmonization is needed for tPSA and fPSA methods.

Introduction
Prostate cancer is the second leading cause of cancer-related deaths for men in the United States.[1] It has been suggested that screening for prostate cancer may have reduced prostate cancer mortality rates, but this remains controversial.[2] Current American Cancer Society guidelines for prostate cancer screening recommend a digital rectal examination and prostate-specific antigen (PSA) measurement annually for all men 50 or older if they have a minimum life expectancy of 10 years.[3] Although PSA is cleared by the Food and Drug Administration for monitoring patients with prostate cancer for disease recurrence, it is unique in that it is the only tumor marker that is currently approved by the Food and Drug Administration as an aid in the detection of prostate cancer. PSA testing for prostate cancer detection, however, is complicated for many reasons. First, PSA exists in multiple isoforms. Although there are many complexed forms that circulate in low concentrations in blood, the 2 principal forms that are measured by current methods are PSA complexed with α1-antichymotrypsin (complexed PSA) and uncomplexed, or free, PSA (fPSA). Many automated analyzers have assays to measure total PSA (tPSA), and most can measure at least 1 of the 2 principal forms directly.

Second, screening with PSA is problematic because PSA is really an organ-specific marker for the prostate rather than a specific marker for cancer. Controversy exists regarding the medical decision levels for tPSA and percentage of fPSA within the United States and abroad.[4] For tPSA concentrations, a diagnostic gray zone exists for patients with PSA concentrations between 4.0 and 10.0 ng/mL (4.0-10.0 µg/L). Many patients with PSA concentrations greater than 10.0 ng/mL (10.0 µg/L) have advanced disease, but within this gray zone only 25% have cancer, and controversy exists whether these are the patients who have early-stage disease and would benefit from detection or whether these are the patients who have indolent forms of prostate cancer. Therefore, recommendations indicate that a biopsy should be performed in any patient with a tPSA result that is greater than 10.0 ng/mL (10.0 µg/L), and further investigation is warranted in patients who are in the diagnostic gray zone and have a result between 4.0 and 10.0 ng/mL (4.0-10.0 µg/L) tPSA.[5-9] In high-risk populations, a biopsy is recommended if the tPSA is 2.5 ng/mL (2.5 µg/L) or more.[3] It has been recently suggested that this lower tPSA cutoff should be adopted for screening men of all ages.[10] Although the medical decision points for percentage of fPSA are also equally controversial, it is generally accepted that measuring fPSA and calculating the percentage of fPSA aids in distinguishing cancer from other benign prostate conditions such as benign prostate hyperplasia, particularly for the population in the diagnostic gray zone.[3,11,12] The lower the fPSA/tPSA ratio, the greater the likelihood of cancer.[11] Currently, biopsy is recommended for 15%, 20%, or 25% fPSA.[11,13,14]

Third, PSA measurements are further complicated by the fact that different assays measure different PSA isoforms to varying extents. Although a certain amount of variation is inevitable because different methods have antibodies that recognize different epitopes of PSA, ideally, assays that measure tPSA should be equimolar and unbiased in the detection of free and complexed PSA. Historically, however, different assays have produced significantly different results for PSA on the same sample. Although lack of an equimolar response was in part responsible for this phenomenon, the other problem was the lack of calibration against a universal standard. In an effort to standardize PSA methods, the World Health Organization (WHO) developed a standard, the WHO (90:10) (National Institute for Biological Standards and Control 96/670) PSA reference preparation, that consists of 90% PSA complexed to α1-antichymotrypsin and 10% fPSA.[15] Recent studies evaluated automated methods using this standard, and although bias between different methods has been significantly reduced, results between assays are not interchangeable for tPSA or fPSA,[16-19] which complicates absolute PSA value recommendations for tPSA cutoffs and interpretation of the fPSA/tPSA ratio.
The aim of our study was to compare 6 commercially available automated methods for PSA concentrations (total and free) by using real patient samples that would minimize matrix effects to determine the degree of method-dependent bias in patient results at critical cutoffs. Our study is unique not only because we evaluated differences using Passing-Bablok analysis but also because statistical differences between methods and concordance at critical cutoffs were determined.

Materials and Methods
A total of 157 surplus samples submitted to our laboratory for PSA testing with results of 2.0 to 10.0 ng/mL (2.0-10.0 µg/L) on the ARCHITECT i2000SR (Abbott Diagnostics, Abbott Park, IL) were selected and further evaluated by 6 additional automated methods. The institutional review board of the University of Utah, Salt Lake City, approved all studies using human samples.

The methods included the ADVIA Centaur (Siemens Diagnostics, Tarrytown, NY), AxSYM (Abbott Diagnostics), IMMULITE 2000 (Siemens Diagnostics), Modular E170 (Roche Diagnostics, Indianapolis, IN), UniCel DxI 800 (Beckman Coulter, Brea, CA) and VITROS ECi (Ortho-Clinical Diagnostics, Raritan, NJ). The ARCHITECT i2000SR was used as the comparison method. Specimens were tested for PSA and free or complexed PSA as available, according to manufacturers' package instructions. In the case of the ADVIA Centaur, by which only total and complexed forms are measured, the following equation was used to estimate fPSA: tPSA – complexed PSA = fPSA. The percentage of fPSA was calculated for all methods using the equation: (fPSA/tPSA) × 100 = % fPSA.

Method comparison studies were conducted using the ARCHITECT i2000SR as the comparison method because it has been demonstrated that this method is equimolar and well standardized to the WHO PSA standard for measuring tPSA and fPSA concentrations.[16,17] Passing-Bablok analysis was performed using Analyse-It, version 1.71 (Analyse-It Software, Leeds, England). The intermethod difference was estimated by using the equation:
Difference = [(a + b) × Xc] – Xc
where a is the y-intercept, b is the slope (as determined from the Passing-Bablok analysis), and Xc is the critical concentration. Critical concentrations of 2.5, 4.0, and 10.0 ng/mL (2.5, 4.0, and 10.0 µg/L) were chosen for tPSA and 15%, 20%, and 25% for percentage of fPSA. A 10% relative bias limit was chosen based on studies by Roddam et al[16,20] that demonstrated that bias of more than 10% significantly impacts the clinical classification of patients.

The Wilcoxon signed rank test was used to evaluate PSA paired comparisons for all samples (PSA, fPSA, and percentage of fPSA) on each method vs the ARCHITECT i2000SR. The κ statistic was used to evaluate concordance with the comparison method at the critical cutoffs of 2.5 and 4.0 ng/mL (2.5 and 4.0 µg/L) for tPSA and 15%, 20%, and 25% for percentage of fPSA. The Wilcoxon signed rank test was performed using R software package, version 2.5 (R Foundation for Statistical Computing, 2007), and κ values were calculated using SAS software v.9.1.3 (SAS Institute, Cary, NC).

Results
Results for tPSA for the 6 automated methods and the ARCHITECT i2000SR comparison method are shown Figure 1. The slopes ranged from 0.836 to 1.143 for the ADVIA Centaur and VITROS ECi methods, respectively. The y-intercepts ranged from –0.02 to 0.34 ng/mL for the AxSYM and VITROS ECi methods, respectively. The correlation coefficients ranged from 0.95 to 0.97. Results for fPSA for 5 methods and the ARCHITECT i2000SR comparison method are shown Figure 2. The slopes ranged from 0.870 to 1.046 for the UniCel DxI 800 and AxSYM methods, respectively. The y-intercepts ranged from 0.02 ng/mL for the AxSYM and IMMULITE 2000 methods to 0.23 ng/mL for the Modular E170 method. The correlation coefficients ranged from 0.87 to 0.99 for the IMMULITE 2000 and AxSYM methods, respectively. Results for the percentage of fPSA for 5 methods and the ARCHITECT i2000SR comparison method are shown Figure 3. The slopes ranged from 0.728 to 1.080 for the UniCel DxI 800 and AxSYM methods, respectively. The y-intercepts ranged from –0.32% to 6.64% for the AxSYM and Modular E170 methods, respectively. The correlation coefficients ranged from 0.89 to 0.97, for the IMMULITE and AxSYM methods, respectively.

Wilcoxon signed rank statistical analysis of the distribution of results for tPSA concentrations gave P values less than .001 with the exception of the AxSYM (P = .093; Figure 1). For fPSA concentrations, all methods gave P values less than .001 except the ADVIA Centaur (P = .686; Figure 2). For percentage of fPSA, all methods had P values less than .001.

For tPSA, at a critical concentration of 2.5 ng/mL (2.5 µg/L), a relative difference of 10% was exceeded by all methods except the AxSYM Table 1 . The κ values for tPSA studies at the critical concentration point of 2.5 ng/mL (2.5 µg/L) ranged from –0.01 to 0.56, for the VITROS ECi and Modular E170, respectively Table 2 . At a critical concentration of 4.0 ng/mL (4.0 µg/L), a 10% relative difference was exceeded by 4 of 6 methods, the exceptions being the AxSYM and E170 ( Table 1 ). At this critical concentration, the κ values ranged from 0.52 for VITROS ECi to 0.90 for the Modular E170 and UniCel DxI 800 ( Table 2 ). At a critical concentration of 10.0 ng/mL (10.0 µg/L), a relative difference of 10% was exceeded by 3 methods ( Table 1 ). These were the ADVIA Centaur, IMMULITE 2000, and VITROS ECi. For the percentage of fPSA Table 3 , at 15% and 20% fPSA, the 10% relative difference limit was exceeded by all methods that were evaluated except the AxSYM. At a critical concentration of 25% fPSA, the ADVIA Centaur, IMMULITE 2000, and UniCel DxI 800 methods exceeded the 10% relative difference limit, whereas the AxSYM and Modular E170 methods did not. For percentage of fPSA studies, the κ values ranged from 0.63 (IMMULITE 2000) to 0.87 (AxSYM) at a critical cutoff of 15% fPSA Table 4 . At 20% fPSA, the κ values ranged from 0.61 (IMMULITE 2000) to 0.90 (AxSYM), and at 25% fPSA, the range was 0.58 (IMMULITE 2000) to 0.83 (AxSYM).

Discussion
Our studies demonstrate that all tPSA assays tested showed good correlation in a concentration range from 2.0 to 10.0 ng/mL (2.0-10.0 µg/L). The fPSA and percentage of fPSA results associated with samples also demonstrated good correlations. The results of Passing-Bablok analysis for tPSA and fPSA methods were consistent with the results of previously published studies.[17,18] Wilcoxon signed rank test results demonstrated that all methods were significantly different from the ARCHITECT i2000SR except the AxSYM for tPSA and that all methods except the ADVIA Centaur were significantly different from the ARCHITECT i2000SR for fPSA. All methods were significantly different from the ARCHITECT i2000SR for percentage of fPSA. Furthermore, when we examined the relative difference between assays for tPSA at clinical decision concentrations of 2.5, 4.0, and 10.0 ng/mL (2.5, 4.0, and 10.0 µg/L), the majority of the assays exceeded a 10% relative difference limit. In addition, concordance studies using the κ statistic and a suggested cutoff of 0.75 or more as a measure of excellent concordance[21] demonstrated that at the medical decision threshold of 2.5 ng/mL (2.5 µg/L), none of the methods were acceptable, and at 4.0 ng/mL (4.0 µg/L), only 3 of the 6 methods (AxSYM, Modular E170, and UniCel DxI 800) were comparable to the ARCHITECT i2000SR. These data, together with Passing–Bablok and Wilcoxon signed rank analyses, suggest that significant assay bias is present and clinical categorization of patients may be different, depending on which assay is used.

The difference between methods was even more pronounced when the percentage of fPSA was examined. At the clinical decision thresholds of 15% and 20%, all methods except the AxSYM had 10% or more relative difference when compared with the ARCHITECT i2000SR comparison method. This is particularly troubling because 20% fPSA is most often recommended as a clinical decision threshold.[11] Both tPSA and fPSA bias may have contributed to the differences in the percentage of fPSA. At a cutoff of 25% fPSA, 3 of the 6 methods showed good agreement. These data suggest that harmonization efforts should focus on percentage of fPSA values of 20% or less.

Method comparison differences for tPSA and fPSA results were least pronounced for the AxSYM compared with the ARCHITECT i2000SR comparison method. This finding may be explained in part by the fact that the ARCHITECT i2000SR and AxSYM are calibrated against the same WHO standard and use the same antibodies, although the detection method for the ARCHITECT i2000SR is chemiluminescence and that for the AxSYM is fluorescence. The ARCHITECT i2000SR, AxSYM, Modular E170, and IMMULITE 2000 are all calibrated against the WHO standard for tPSA; the ADVIA Centaur is calibrated to a purified PSA standard that is traceable to the WHO standard; and the VITROS ECi and UniCel DxI 800 are calibrated using a purified PSA standard.[17,22,23] For fPSA, the ARCHITECT i2000SR, AxSYM, Modular E170, and IMMULITE 2000 are calibrated using a WHO standard. The ADVIA Centaur, VITROS ECi, and UniCel DxI 800 are calibrated using other standards, such as purified PSA.[17,22-24]
Our studies demonstrate that when comparing automated PSA assays using patient samples, all methods correlate, but further harmonization efforts are required for clinical concordance. There is growing evidence that despite standardization attempts, significant differences still exist in automated PSA methods.[16-19] The current PSA methods still cannot be used interchangeably as demonstrated by the more than 10% relative differences between methods at relevant medical decision concentrations, making PSA interpretation difficult. Lack of agreement at critical concentrations for tPSA of 2.5, 4.0, and 10.0 ng/mL (2.5, 4.0, and 10.0 µg/L) and for percentage of fPSA of 15%, 20%, and 25% can potentially result in misclassification of patients.[18] Because clinically the decision for further diagnostic procedures such as prostate biopsy is made based on the tPSA and fPSA results at these critical concentrations, the lack of harmonization and its potential impact on patient care remain concerns.

Table 1. Summary of Bias Estimates for Total Prostate-Specific Antigen for Six Methods Compared With the ARCHITECT i2000SR Comparison Method*

Table 2. Summary of κ Statistics for Total Prostate-Specific Antigen for Each Method Compared With the ARCHITECT i2000SR Comparison Method

~Patricia R. Slev, PhD; Sonia L. La'ulu; William L. Roberts, MD, PhD
~Am J Clin Pathol. 2008;129(6):952-958. ©2008 American Society for Clinical Pathology
~Posted 06/25/2008

(Source: Medscape)

"Anti-HBc Alone" Reflects Occult Hepatitis B Infection

2008-05-09T22:52:00.000+08:00

NEW YORK (Reuters Health) Apr 29 - Serum antibodies to hepatitis B virus (HBV) core antigen (anti-HBc) in isolation may serve as a marker of occult infection with HBV, according to a report in the April issue of the Journal of Medical Virology.

Occult HBV infection is defined as the presence of HBV DNA in blood or liver in the absence of detectable HBV surface antigen (HBsAg) in serum, the authors explain, and previous studies have associated occult HBV infection with the progression of chronic liver disease in patients infected with hepatitis C (HCV).

Dr. Francesco Vitale from Universita degli Studi di Palermo, Italy and colleagues evaluated the prevalence of isolated anti-HBc and its possible value as a serologic marker for detection of HBV DNA in HBsAg-negative/anti-HBc-positive patients with or without HCV infection.

The prevalence of "anti-HBc alone" was 1.8% among asymptomatic subjects, 10.2% among drug users, and 21.5% among patients with hepatocellular carcinoma, the authors report.

More than half the individuals with anti-HBc in isolation (57.4%) were anti-HCV positive, including more than 85% of drug users and hepatocellular carcinoma patients with isolated anti-HBc.

Four percent of the sera with anti-HBc alone contained HBV genomes, the researchers note, including 5.9% of those without HCV antibodies, 3.2% of drug users, and 4.8% of hepatocellular carcinoma patients.

"This serologic pattern could be useful for further clinical investigations," Dr. Vitale and colleagues conclude. "Surely, a definitive assessment of this serological pattern as a sentinel marker for 'occult HBV' would require molecular investigation of individuals without, as well as with, 'anti-HBc alone'."

"The ultimate goal is to define the infectivity and clinical consequences of persons with these atypical serologic and molecular patterns of HBV infection," they add.

J Med Virol 2008;80:577-582.

(Source: Medscape)

Neutrophil-To-Lymphocyte Ratio Prognostic in MI Patients by Megan Rauscher

2008-05-09T22:46:00.002+08:00

NEW YORK (Reuters Health) Apr 29 - Results of a study establish that neutrophilia and lymphopenia, expressed as a high neutrophil-to-lymphocyte ratio (N/L), are strongly related to long-term mortality in patients with ST-segment elevation myocardial infarction (STEMI).

"This ratio showed higher discriminative ability than total white blood cell count," Dr. Julio Nunez from the University of Valencia, Spain, noted in comments to Reuters Health.

Dr. Nunez and colleagues determined the association of N/L maximum value with mortality and compared its predictive ability with total white blood cell maximum count (WBC) in 470 STEMI patients admitted to a single university hospital. Measurements were obtained at admission and daily for the first 96 hours after admission. During a median follow up of 3 years, 106 patients died (22.6%).

"In this study, we showed that N/L-max measured within the first 96 hours after onset of STEMI symptoms carried significant prognostic value for subsequent mortality," the authors report in the March 15 issue of the American Journal of Cardiology.

The mortality rate during follow up in the first quintile of N/L-max was 6.4%. The highest mortality rates were seen in patients in the fourth and fifth quintiles -- 34% and 47.9%, respectively -- which translated to hazard ratios of 2.58 and 4.20, respectively.
"This association remained significant after adjusting for key predictors including age, reperfusion criteria, renal function, and surrogates of myocardial extensions, such as left ventricular dysfunction, systolic blood pressure and Killip's classification," the investigators note.
The overall discriminatory ability of N/L-max was superior to that of WBC-max, they also report.

These findings were not unexpected, Dr. Nunez told Reuters Health, "because inflammation response is associated with adverse prognosis in the setting of acute coronary syndromes, and commonly this response is characterized by neutrophilia and lymphopenia, so N/L seems a better inflammation marker than total white blood cells."

His group hypothesizes that "patients with high N/L ratio during the acute phase of myocardial infarction could be a subgroup with higher benefit from an aggressive treatment."
"Further studies are needed to clarify this point," Dr. Nunez said.

Am J Cardiol 2008;101:747-752.

(Source: Medscape)

Fleshy Lesions on a 32-Year-Old Woman

2008-03-23T23:03:00.002+08:00

Background

A 32-year-old woman presents to the emergency department (ED) with several flesh-colored papules on her face, trunk, and upper extremities.

She first noticed the lesions at approximately 10 years of age; however, over the past 5 years, the lesions have increased in number and become uncomfortable. She primarily complains of irritation from the lesions along her bra line. She underwent excision of similar skin lesions 5 years ago, but they have since recurred. She denies having any discharge, pain, trauma, contact with individuals with atypical skin lesions or rashes, travel out of the country, unusual exposure to animals, or a history of sexually transmitted diseases.

The patient's medical and surgical history includes environmental allergies, frequent episodes of bronchitis, and the aforementioned excisions. She has no known drug allergies, and she takes cetirizine HCl and fluticasone propionate for seasonal allergies. Her family history is significant for coronary artery disease, hypertension, diabetes mellitus, and glaucoma, but there is no family history of similar lesions. She does not smoke and only drinks alcohol on occasion. The review of her systems is otherwise unremarkable.

The physical examination reveals dozens of 0.5-2.0 cm fleshy nodules spread over her trunk, face, and upper extremities. The nodules are nontender to palpation and nonerythematous, and they produce no discharge, crusting, or scaling. Several tan oval macules measuring 1.5-3 cm in size and patches with well-defined borders are located on her trunk and upper extremities (see Images). Her vital signs are within normal limits, and her other physical findings are unremarkable.

Discussion
Neurofibromatosis (NF) is an autosomal dominant disorder with numerous presentations that can affect nearly every organ system. The 2 major subtypes of NF are peripheral NF, also known as NF type 1 (NF1), and central NF, which is referred to as NF type 2 (NF2). These terms are not completely accurate, however, because NF1 also can include central nervous system (CNS) abnormalities.

About 50% of cases of NF are familial; the other 50% are caused by spontaneous gene mutation. NF1, also known as von Recklinghausen disease, is a common genetic disorder involving a mutation in the gene that produces neurofibromin on chromosome 17; the condition affects 1 in every 3000-4000 births.[1] All races are affected, and the 2 sexes are affected equally.[3] Two or more of the following 7 criteria must be present in order to make the diagnosis of NF1: 6 or more café-au-lait spots (irregularly shaped, evenly pigmented, brown macules), 2 or more neurofibromas, axillary or inguinal freckling, Lisch nodules (hamartomas of the iris), optic gliomas, various types of osseous lesions, and a first-degree relative with the condition.

Symptomatic NF1 typically initially manifests as café-au-lait spots that may be present at birth or that appear over time during childhood. Axillary or inguinal freckles are not usually present at birth but, rather, appear throughout childhood and adolescence. Neurofibromas are rarely seen in young children but usually appear over time in older children, adolescents, and adults. The patient may have as few as 3 or as many as thousands of these benign lesions, which consist of Schwann cells, neural fibroblasts, mast cells, and vascular elements. The neurofibromas may occur anywhere in the body and can potentially lead to marked disfigurement. If the lesions are deep, they may only be detected through palpation; cutaneous lesions may initially appear as small papules on the trunk, the extremities, the scalp, or the face. A specific type of these lesions is a plexiform neurofibroma, which is a more diffuse type of growth that can be locally invasive and quite deep. These lesions may be associated with bony erosion and pain, and they may also be accompanied by overlying hyperpigmentation or hypertrichosis. The onset of puberty or pregnancy may be associated with an increased number of neurofibromas, as well as an increase in the speed of preexisting lesion growth. Lesions along visual, auditory, or CNS nerve pathways may result in blindness, deafness, or neurologic deficits. On histology, the neurofibromas are generally well-differentiated tumors that contain elongated spindle-shaped cells and pleomorphic fibroblast-like cells. Some lesions may contain inflammatory cells. Occasionally, a large neurofibroma, a deep plexiform neurofibroma, or a peripheral nerve sheath tumor residing within the brachial or pelvic plexus may undergo malignant transformation into a neurofibrosarcoma. Unlike benign neurofibromas, neurofibrosarcomas are characteristically hypercellular, with giant cells, increased numbers of mitoses, and vascular proliferation. Additionally, small masses of malignant cells may be present within larger masses of benign cells (eg, as in a plexiform neurofibroma).

Optic nerve tumors occur primarily in children younger than 5 years. The most common presenting symptom is asymmetric, noncorrectable visual loss, but subtle peripheral field defects, optic nerve pallor, color-discrimination difficulties, or proptosis may be present without visual acuity being affected. A slow-growing optic nerve glioma (ONG) may lead to vision problems in some older children and adolescents; these patients should be monitored for visual difficulties throughout childhood and adulthood. In adults, a visually insignificant ONG may be detected incidentally on head imaging studies. Although Lisch nodules are usually not visible without use of a slit lamp, they may occasionally be seen with a direct or indirect ophthalmoscope, especially in individuals with light-colored irises. Choroidal abnormalities with a patchy appearance or retinal corkscrew vascular changes may also be noted on funduscopic examination.

Orthopedic manifestations are also commonly encountered. Congenital pseudarthrosis may be evident at birth; bowing of the tibia is the most typical presentation. Thinning and angulation of the long bones can occur throughout early childhood and adolescence, with prominence of the anterior tibia and progressive deformity; less commonly, bowing of the forearm can occur. Scoliosis with or without kyphosis may become evident in childhood or adolescence; when this finding is present in children younger than 10 years, scoliosis is associated with a poor prognosis and is likely to progress rapidly. Scoliosis detected during adolescence should still be monitored clinically, but it is much less likely to require orthopedic intervention. Sphenoid bone dysplasia is usually asymptomatic, but it can occasionally be associated with herniation through the bony defect. Other skeletal anomalies, such as fibrous dysplasia, subperiosteal bone cysts, or vertebral scalloping, can also be found.

Rare complications of NF1 include renal arterial stenosis and pheochromocytoma, either of which can present with hypertension.

NF2 is a progressive genetic disorder that is present in 1 in every 33,000-40,000 births.Patients with NF2 (which results from an abnormality on chromosome 22) typically present with acoustic neuromas or vestibular schwannomas. The clinical manifestations of NF2 include tinnitus, balance disorders, and progressive hearing loss. Affected patients may also have meningiomas, juvenile cataracts, or schwannomas of the dorsal roots of the spinal cord. The diagnosis of NF2 is based on the presence of bilateral acoustic neuromas or a unilateral acoustic neuroma in a first-degree relative with NF2.

For both NF1 and NF2, the diagnosis is primarily based on the physical findings and a positive family history. Plain radiologic studies, which may detect many bony abnormalities (such as modeling defects of the long bones or ribs, bony erosion secondary to an adjacent plexiform neurofibroma, or scoliosis), may be useful diagnostic tests. Gadolinium-enhanced magnetic resonance imaging (MRI) of the brain is the preferred diagnostic imaging study of the head, and it can be ordered either routinely—as a standard screening—or it can be ordered for patients with specific indications, such as the onset of neurologic problems or headaches. MRI studies have been shown to frequently detect unidentified bright objects in the brain parenchyma; generally, these bright spots do not enhance, they cause no mass effect, and they often resolve as the patient gets older. It has been theorized that these masses may represent benign hamartomas. MRI scanning of the brain can assist in evaluating the optic nerves or optic chiasm. This imaging modality is also useful for diagnosing and evaluating other internal lesions, such as mediastinal masses, spinal cord tumors, deep plexiform neurofibromas, neurofibromas of the brachial or sacral plexus, and abdominopelvic lesions. Genetic analyses and psychological or developmental assessments should also be part of the evaluation of patients with neurofibromas.

No cure exists for NF1 or NF2. The recommendations for follow-up include referral to support groups, psychological counseling, and evaluation for learning disorders; potential surgical excision of the lesions; and regular monitoring by a primary care provider for any lesion changes (patients with NF1 are at a somewhat increased risk for malignancy). Annual ocular examinations are recommended. Genetic testing is also available for patients with NF who wish to have children. Historically, surgery has been a successful treatment for the lesions themselves; however, there is often recurrence, and nerve damage is a risk in cases in which the lesions are located along neural pathways.

(Source: Medscape)

Guidelines Issued for Early Detection of Colorectal Cancer

2008-03-22T22:57:00.002+08:00

News Author: Laurie Barclay, MDCME
Author: Penny Murata, MD

March 10, 2008 — The American Cancer Society has issued guidelines for the screening and surveillance for the early detection of colorectal cancer (CRC) and adenomatous polyps in asymptomatic, average-risk adults. The new consensus guidelines, which were jointly developed with the US Multi-Society Task Force on Colorectal Cancer and the American College of Radiology, beginning in 2006 to 2007, are published in the March 5 First Look issue of CA: A Cancer Journal for Clinicians and will appear in the May-June 2008 print issue.

"In the United States, colorectal cancer (CRC) is the third most common cancer diagnosed among men and women and the second leading cause of death from cancer," write Bernard Levin, MD, from The University of Texas M.D. Anderson Cancer Center in Houston, Texas, and colleagues from the American Cancer Society Colorectal Cancer Advisory Group, the US Multi-Society Task Force, and the American College of Radiology Colon Cancer Committee. "CRC largely can be prevented by the detection and removal of adenomatous polyps, and survival is significantly better when CRC is diagnosed while still localized."

This update of each contributing organization's guidelines groups screening tests into those that primarily detect cancer early and also can detect adenomatous polyps, thus offering a greater potential for prevention through polypectomy.

Clinicians should make patients aware of the full range of screening options whenever feasible. At a minimum, however, clinicians should be prepared to offer patients a choice between a screening test that is effective at both early cancer detection and cancer prevention through the detection and removal of polyps and a screening test for which benefits are primarily limited to early detection of cancer. The 3 sponsoring organizations strongly concur that the main goal of screening should be the prevention of CRC.

"In the last decade, there has been an increase in the number of technologies available for CRC screening, and in the case of stool tests, there has been growth in the number of commercial versions of guaiac-based and immunochemical-based stool tests (gFOBT [guaiac-based fecal occult blood test] and FIT [fecal immunochemical test])," the authors of the guidelines write. "It is our hope that these new recommendations will facilitate increased rates of CRC screening and that referring clinicians find these new guidelines ease some of the challenges they have experienced in promoting CRC screening to their patients."

In the first phase of the guidelines update process, stool tests were reviewed, including the gFOBT, the FIT, and the stool DNA test (sDNA). In the second phase, the panel developed recommendations for the structural examinations, including flexible sigmoidoscopy (FSIG), colonoscopy, double-contrast barium enema (DCBE), and computed tomographic (or virtual) colonography (CTC).

The panel discussed these issues, heard presentations from outside experts, relied on previous evidence-based reviews, and searched MEDLINE (National Library of Medicine) and bibliographies of identified articles for literature related to CRC screening and specific to individual tests published between January 2002 and March 2007. When evidence was insufficient to provide a clear, evidence-based conclusion, final recommendations were based on expert opinion.

Testing options for the detection of adenomatous polyps and cancer for asymptomatic adults 50 years and older include FSIG every 5 years, colonoscopy every 10 years, DCBE every 5 years, or CTC every 5 years.

Testing options that primarily detect cancer in asymptomatic adults 50 years and older include annual gFOBT with high-test sensitivity for cancer; annual FIT with high-test sensitivity for cancer; or sDNA with high-test sensitivity for cancer, although the optimal interval for sDNA is uncertain.

Each screening test has unique advantages, has been shown to be cost-effective, and has associated risks and limitations. Ultimately, patient preferences and availability of testing resources guide the selection of screening tests.

The disadvantages of the structural tests are that they require bowel preparation, but their primary advantage is that they can detect polyps as well as cancer. Conscious sedation is used for colonoscopy. FSIG is uncomfortable, and screening benefit is limited to the portion of the colon that is directly examined.

Risks for colonoscopy, DCBE, and CTC may rarely include perforation; colonoscopy may also be associated with bleeding. Positive findings on FSIG, DCBE, and CTC usually result in referral for colonoscopy.

The advantages of the stool tests are that they are noninvasive, they do not require a bowel preparation, they can be done in the privacy of the patient's home, and they are more readily available to patients without adequate insurance coverage or local resources.
However, these noninvasive tests are less likely to prevent cancer vs the invasive tests; they must be repeated at regular intervals to be effective; and, if the test is abnormal, an invasive test, namely colonoscopy, will be required. For patients who are unwilling to have repeated testing or to undergo colonoscopy if the test results are abnormal, stool testing is ineffective and should not be recommended.

This update of the CRC screening guidelines focused on screening in average-risk adults and did not consider evidence concerning CRC screening or surveillance for individuals at increased and high risk. Patients with a personal history of adenomatous polyps or curative-intent resection of CRC, a family history of either CRC or colorectal adenomas diagnosed in a first-degree relative before age 60 years, or a history of inflammatory bowel disease of significant duration or 1 of 2 hereditary syndromes should continue to follow recommendations issued previously by the American Cancer Society or the US Multi-Society Task Force for individuals at increased risk.
"There is compelling evidence to support screening average-risk individuals over age 50 years to detect and prevent CRC," the panel concludes. "Screening of average-risk individuals can reduce CRC mortality by detecting cancer at an early, curable stage and by detecting and removing clinically significant adenomas. . . . No CRC screening test is perfect, either for cancer detection or adenoma detection."

Some of the authors of the guidelines have disclosed various financial relationships with Exact Sciences, Vital Images, Medicsight, Covidien, Viatronix, Fleet, Olympus, Given Imaging, Avantis, NeoGuide, G.I. View, American BioOptics. Genzyme, Epigenomics, GeneNews, and licensure of a CT colonography software patent to GE Medical Systems.

CA Cancer J Clin. Published online March 5, 2008.

Clinical Context
CRC is the third most common cancer in men and women in the United States and is the second leading cause of deaths from cancer, as reported by Jemal and colleagues in the March-April 2008 issue of CA: A Cancer Journal for Clinicians. Tools for CRC screening include stool tests for occult blood or exfoliated DNA to detect cancer and structural examinations to detect adenocarcinoma and identify adenomatous polyps. Stool tests include the gFOBT, the FIT, and the sDNA. Structural examinations include FSIG, colonoscopy, DCBE, and CTC.

The American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology have collaborated on guidelines for the detection of adenomatous polyps and CRC in asymptomatic, average-risk adults 50 years or older.

Pearls for Practice
Stool test screening options to detect CRC in asymptomatic, average-risk adults 50 years and older include the annual high-sensitivity gFOBT, the annual FIT, or the sDNA test at uncertain intervals.

Structural examination screening options to detect CRC and adenomatous polyps in asymptomatic, average-risk adults 50 years and older include FSIG every 5 years, colonoscopy every 10 years, DBCE every 5 years, or CTC every 5 years.

(Source: Medscape)

NT-ProBNP Level Best Prognostic Indicator for Advanced Heart Failure

2008-02-07T19:44:00.000+08:00

NEW YORK (Reuters Health) Jan 29 - New research indicates that the plasma level of NT-proBNP is a better prognostic indictor than the glomerular filtration rate (GFR) estimated with standard equations in patients with advanced heart failure.

As reported in the European Heart Journal for December, Dr. Roy S. Gardner, from the Royal Infirmary in Glasgow, UK, and colleagues assessed NT-proBNP levels and GFR (estimated with the modification of diet in renal disease equations) in 182 patients with advanced heart failure who were being considered for cardiac transplantation. The median follow-up period was 642 days.

During follow-up, 40 patients died, 4 required urgent cardiac transplantation, and another 29 underwent non-urgent transplantation.

On univariate analysis, GFR predicted all-cause mortality. On multivariate analysis, however, only the NT-proBNP level was a significant independent predictor of all-cause mortality or the combined endpoint of all-cause mortality or urgent transplantation.

The current study "represents an important step forward regarding the utility of NT-proBNP testing in patients with impaired renal function," Dr. James L. Januzzi, from Massachusetts General Hospital in Boston, and colleagues write in a related editorial.

The findings indicate that NT-proBNP "is strongly prognostic for death and/or urgent cardiac transplantation even in the presence of renal impairment," they add.

Eur Heart J 2008;28:2960-2961,3027-3033.

Source: Medscape

I Love Garfield!

2008-02-07T19:27:00.000+08:00

Random Case of the Day - 56 year old female with an incidental cardiac mass identified on chest X-ray.

2008-02-06T19:39:00.000+08:00

DIAGNOSIS: Cardiac myxoma

This lesion features myxoid stroma and bland stromal cells which cluster around blood vessels. There’s a background of chronic inflammation, and hemosiderin deposition onto elastic fibers. Also on the slide there are areas of superimposed organizing thrombus. These findings are diagnostic of a cardiac myxoma.

An organizing thrombus would lack the extensive myxoid areas with characteristic perivascular spindle cells of cardiac myxoma. Mucinous carcinoma and myxofibrosarcoma would show greater degrees of cytologic atypia, and can also be excluded by clinical history.

Cardiac myxomas are part of the Carney Complex, which includes cutaneous pigmentation around the lips, cardiac myxoma, cutaneous angiomyxoma, myxoid fibroadenoma, pigmented nodular adrenal cortical disease, large cell calcifying Sertoli cell tumor of the testis, pituitary adenoma, blue nevi and, psammomatous melanotic schwannoma.

Source: Johns Hopkins Surgical Pathology Conference

Screening Pregnant Women for Bacterial Vaginosis Not Recommended

2008-02-06T16:57:00.000+08:00

News Author:
Laurie Barclay, MDCME

Author: Laurie Barclay, MD

February 4, 2008 — The US Preventive Services Task Force (USPSTF) recommends against clinicians screening for bacterial vaginosis in asymptomatic pregnant women who are at low risk for premature delivery, according to the results of an updated review and guidelines reported in the February 5 issue of the Annals of Internal Medicine.

"The associations between bacterial vaginosis and adverse pregnancy outcomes, such as preterm delivery, are well documented," the USPSTF writes. "Good-quality evidence indicates that screening tests (the Amsel clinical criteria or Gram stain) can detect bacterial vaginosis."
The USPSTF review suggests that there is good evidence that screening for bacterial vaginosis does not benefit pregnant women at low risk for premature delivery, and the expert USPSTF panel therefore recommends against screening low-risk women for bacterial vaginosis.
Among women of reproductive age, bacterial vaginosis is the most common lower genital tract syndrome, and it has been associated with premature births or low birthweight. Because it is easy to screen for and treat bacterial vaginosis, some experts have recommended screening all pregnant women for this condition. However, in this review, the USPSTF finds insufficient evidence to recommend either for or against screening for the syndrome in pregnant women at high risk for premature delivery.

The USPSTF identified new evidence that addressed gaps identified in the previous 2001 USPSTF recommendation, and they weighed the benefits and harms of screening for bacterial vaginosis in pregnancy in light of the new evidence. A search of MEDLINE, Cochrane Library databases, and the Database of Abstracts of Reviews of Effects identified published literature on this topic, and the panel also systematically reviewed reference lists and consulted with experts in this field.

When appropriate based on the available data, a series of meta-analyses, using both newly identified data and those contained in the 2001 report, allowed estimation of the pooled effect of treatment of bacterial vaginosis on preterm delivery (before 37, 34, or 32 weeks) and on low birthweight and preterm, premature rupture of membranes.

Based on this review and meta-analyses, the USPSTF panel concluded that current evidence is insufficient to evaluate the balance of benefits and harms of screening for bacterial vaginosis in pregnant women at high risk for preterm delivery (I statement).

The USPSTF panel issued the recommendation not to screen for bacterial vaginosis in pregnant women at low risk for preterm delivery (D level recommendation).

In asymptomatic pregnant women at low risk for preterm delivery, studies are lacking, and evidence is therefore poor, for harms of screening for bacterial vaginosis. However, evidence is fair that false-positive results from screening lead to harms caused by treatment.
In asymptomatic pregnant women at high risk for preterm delivery, studies are lacking, and evidence is therefore poor, for harms of screening for bacterial vaginosis. Studies on the harms of treatment have yielded conflicting results in this population.

The overall USPSTF assessment and conclusion is that for asymptomatic pregnant women at low risk for preterm delivery, there is moderate certainty that screening for bacterial vaginosis has no net benefit. For asymptomatic pregnant women at high risk for preterm delivery, the evidence is conflicting, preventing determination of the balance of benefits and harms.
"Available evidence on treatment benefit is conflicting," the USPSTF writes. "Additional research is needed to evaluate the benefit of screening and treating asymptomatic bacterial vaginosis in women at highest risk for preterm delivery."

Risk factors for preterm delivery include African American race, pelvic infection, and previous preterm delivery.

Gram stain or the Amsel clinical criteria can be used to diagnose bacterial vaginosis. Clinical diagnosis by the Amsel criteria requires that 3 or 4 of the following criteria be present: (1) vaginal pH of more than 4.7, (2) presence of clue cells on wet mount, (3) thin homogeneous discharge, and (4) amine "fishy odor" when potassium hydroxide is added to the discharge.
Although the optimal treatment regimen for bacterial vaginosis is unclear, oral or vaginal gel metronidazole and oral or vaginal cream clindamycin are typically used.

"Bacterial vaginosis is more common among African-American women, women of low socioeconomic status, and women who have previously delivered low-birthweight infants," the USPSTF concludes. "Research is also needed to assess which screening tests providers use to diagnose bacterial vaginosis in clinical practice and the accuracy of these tests. Finally, continued research is needed to determine the optimal treatment regimen for bacterial vaginosis."
The Oregon Evidence-based Practice Center under contract to the Agency for Healthcare Research and Quality, Rockville, Maryland, supported this study.
Ann Intern Med. 2008;148:214-219, 220-233.

Clinical Context
In women of childbearing age, bacterial vaginosis is the most frequently documented lower genital tract syndrome. There are well-documented associations between bacterial vaginosis and adverse pregnancy outcomes, including premature birth or low birthweight. Good-quality evidence indicates that screening tests can detect bacterial vaginosis.

Because it is easy to screen for and treat bacterial vaginosis, some experts have recommended screening all pregnant women for this condition. However, in this review, the USPSTF finds insufficient evidence to recommend either for or against screening for the syndrome in pregnant women at high risk for premature delivery.

Pearls for Practice
The USPSTF review suggests that there is good evidence that screening for bacterial vaginosis does not benefit pregnant women at low risk for premature delivery, and the expert USPSTF panel therefore recommends against screening low-risk women for bacterial vaginosis (D level recommendation).

Based on this review and meta-analyses, the USPSTF panel concluded that current evidence is insufficient to evaluate the balance of benefits and harms of screening for bacterial vaginosis in pregnant women at high risk for preterm delivery (I statement).

Source: Medscape