Section 4 -

Three Case Histories Illustrating the Diagnostic Value of Immunohistochemistry in Histologically Difficult Neoplasms Bharat Jasani Department of Pathology, School of Medicine Cardiff University Wales, U.K.

Case 1 A 65 year old male presented with a mass in the left parotid region which had been slowly growing to a size of 3 cm over a period of 3-4 months. He was otherwise well. The mass on imaging studies appeared to be a lymph node adjacent to the parotid gland which otherwise looked normal. The lymph node was excised and submitted for review with a suspected diagnosis of granulomatous inflammation, but T-cell lymphoma could not be excluded. On low power the lymph node showed effaced architecture with a nodular infiltrate and prominent fibrosis. There were areas of necrosis within a polymorphous infiltrate composed of lymphocytes, plasma cells and eosinophils. Scattered giant cells were noted together with some atypical RS-like cells in a histiocyte-rich background. Most of the infiltrate was positive for CD45 including some larger cells, but with very scanty presence of CD20+ cells. Most of the infiltrate was of T-cell phenotype with some of the larger cells appearing to be positive for CD4 but there was no expression of CD30 or CD15. Large numbers of histiocytes were noted, with positivity associated with some of the plump epithelioid cells. Diagnosis of a peripheral T-cell lymphoma was suspected, but PCR analysis indicated polyclonal patterns of amplification with both T and B-cell primers. A search for tumour of non-lymphoid origin was therefore conducted. Pan cytokeratin stain was performed and identified large scattered atypical blasts. These were shown on in situ hybridisation to be positive for EBER. The diagnosis of "lymphoepithelioma-like carcinoma was made" (undifferentiated carcinoma of nasopharyngeal type). The patient's pharynx was investigated and biopsied. One of the blind biopsies of the pharynx showed an inflammatory infiltrate. On closer inspection there were recognised to be scattered atypical blasts positive for AE1/AE3 and also strongly positive for EBER. This type of tumour is very commonly initially diagnosed as a metastasis and is often initially misdiagnosed as lymphoma, and indicates the value of the combined availability of a wide panel of immunohistochemical markers and PCR and in situ hybridisation techniques in a specialist laboratory setting Case 2 A 61 man presented with an irregular prostate on per rectum examination. The serum PSA was not raised. The prostate biopsy was shown to be negative for PSA and prostate specific acid phosphatase (PSAP). Histologically the tumour could not be diagnosed to be of bladder origin. Application of 34betaE12 showed it to be however diffusely strongly positive for this pan keratin marker supporting the diagnosis of a tumour of urothelial origin. Cystoscopy showed a tumour mass growing out of the bladder mucosa. Biopsy of this tumour showed it to be of urothelial origin on histological grounds. The use of a panel of PSA, PSAP and 34betaE12 can be helpful for differentiation of a urothelial tumour from a histologically ambiguous PSA-/PSAP- tumour infiltrating the prostate. ( Varma M, Morgan M, Amin MB, Wozniak S, Jasani B. High molecular weight cytokeratin antibody (clone 34betaE12): a sensitive marker for differentiation of high-grade invasive urothelial carcinoma from prostate cancer. Histopathology. 2003;42:167-72) Case 3 A 58 year old man was admitted as an emergency with a one day history of haematemesis and melaena. He underwent an emergency laparotomy for a tumour in the lesser curve of the stomach. The tumour showed histological features which were difficult to interpret and needed immunohistochemical investigation to definitively diagnose it to be an epithelioid haemangioendothelioma. Surgery in the form of wide excision was conducted as the treatment of choice for this rare neoplasm. Vascular tumours of the stomach are rare, representing 0.9%-3.3% of all gastric neoplasms. This case highlights the difficulty in diagnosing this type of tumour preoperatively and emphasises the need for long term follow up in view of its uncertain metastatic potential. (Sanjay P, Raman S, Shannon J, Williams GT, Woodward. A gastric epithelioid haemangioendothelioma: a rare cause of upper gastrointestinal bleeding. Postgrad Med J. 2005;81:e7)