Metastatic carcinoma from the bladder

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

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

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)