Friday, August 08, 2008

Metastatic carcinoma from the bladder

Metastatic carcinoma from the bladder


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.


(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

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.






Pre-B acute lymphoblastic lymphoma involving the kidneys


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. - Leukemia, Acute chapter

(Source: Pathology Outlines by Dr. Nat Pernick)

Sunday, August 03, 2008

Pruritic plaque with pustules on the nose and cheeks

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.

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

Figs. 2A – K: Histopathology.
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.

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.


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.

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)

Monday, July 14, 2008

50 y/o male with duodenal polyp

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.




Hyperplastic polyp of gastric metaplasia / gastric heterotopia


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.
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.
'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.
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.
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)

Saturday, July 12, 2008

Derm101 Case: Basal Cell Carcinoma, Nodular


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.


(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)

Friday, July 04, 2008

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

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.

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 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).

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)

Friday, May 09, 2008

"Anti-HBc Alone" Reflects Occult Hepatitis B Infection

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

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)