Saumitra S Banerjee

Morphological and immunophenotypic variations in malignant melanoma

A variety of cytomorphological features, architectural patterns and stromal changes may be observed in malignant melanomas. Hence, melanomas may mimic carcinomas, sarcomas, benign stromal tumours, lymphomas, plasmacytomas and germ cell tumours. Melanomas may be composed of large pleomorphic cells, small cells, spindle cells and may contain clear, signet‐ring, pseudolipoblastic, rhabdoid, plasmacytoid or balloon cells. Various inclusions and phagocytosed material may be present in their cytoplasm. Nuclei may show bi‐ or multi‐nucleation, lobation, inclusions, grooving and angulation. Architectural variations include fasciculation, whorling, nesting, trabeculation, pseudoglandular/pseudopapillary/pseudofollicular, pseudorosetting and angiocentric patterns. Myxoid or desmoplastic changes and very rarely pseudoangiosarcomatous change, granulomatous inflammation or osteoclastic giant cell response may be seen in the stroma. The stromal blood vessels may exhibit a haemangiopericytomatous pattern, proliferation of glomeruloid blood vessels and perivascular hyalinization. Occasionally, differentiation to nonmelanocytic structures (Schwannian, fibro‐/myofibroblastic, osteocartilaginous, smooth muscle, rhabdomyoblastic, ganglionic and ganglioneuroblastic) may be observed. Typically melanomas are S100 protein, NKIC3, HMB‐45, Melan‐A and tyrosinase positive but some melanomas may exhibit an aberrant immunophenotype and may express cytokeratins, desmin, smooth muscle actin, KP1 (CD68), CEA, EMA and VS38. Very rarely, neurofilament protein and GFAP positivity may be seen.

Extra-medullary myeloid tumour (granulocytic sarcoma) is often misdiagnosed: a study of 26 cases

To describe the clinicopathological and immunophenotypic features of 26 cases of extra‐medullary myeloid tumour (EMMT)/granulocytic sarcoma, which remains poorly recognized and is frequently confused with malignant lymphoma, and to discuss the main diagnostic problems experienced by the referring pathologist.

Pseudoangiosarcomatous carcinoma: a clinicopathological study of seven cases

Seven cases of carcinoma mimicking angiosarcoma occurring in skin (3 cases), breast (3) and lung (1) are described. The cutaneous, pulmonary and one of the breast carcinomas were poorly differentiated and squamous in type; the other two breast tumours were poorly differentiated ductal carcinomas with focal squamous differentiation. Histologically, the pseudoangiosarcomatous pattern was due to complex anastomosing channels and spaces lined by neoplastic cells. The spaces contained hyaluronic acid. The neoplastic cells exhibited cytokeratin positivity but yielded negative results with the endothelial cell markers, factor VIII‐related antigen and CD 34 (QB‐END/10). Two breast tumours showed binding of UEA‐1. Ultrastructurally, unequivocal epithelial differentiation was demonstrated in six of the cases. Pathogenetically, these tumours appeared to be variants of acantholytic squamous cell carcinoma. Recognition of this unusual form of carcinoma is important, as an incorrect diagnosis of angiosarcoma may lead to inappropriate treatment and prognostication.

Divergent differentiation in malignant melanomas: a review

The aim of this review was to document and discuss diagnostic problems associated with divergent differentiation (‘metaplastic change’) in malignant melanomas, defined as the development in these tumours of morphologically, immunohistochemically and/or ultrastructurally recognizable non‐melanocytic cell or tissue components. Types of divergent differentiation reported in malignant melanoma include: fibroblastic/myofibroblastic, Schwannian and perineurial, smooth muscle, rhabdomyosarcomatous, osteocartilaginous, ganglionic and ganglioneuroblastic, neuroendocrine and probable epithelial. Divergent differentiation is certainly a rare phenomenon and, when it occurs, can be missed by unwary pathologists and lead to diagnostic uncertainty. A carefully chosen immunohistochemical panel and the input of electron microscopy can help to clarify the nature of the cellular differentiation of these tumours and lead to a correct final diagnosis. The clinical significance of such aberrations is uncertain, nor are the underlying mechanisms as yet well defined.

Neuroendocrine carcinomas of the larynx.

The clinical and histopathological characteristics of seven cases of Moderately Differentiated Neuroendocrine Carcinomas (MDNEC) and two cases of Poorly Differentiated Neuroendocrine Carcinomas (PDNEC) have been reviewed. The tumours arose in the supraglottis of predominantly elderly men. Two cases had raised levels of urinary 5-hydroxy-indole-acetic acid at presentation but no case developed the carcinoid syndrome. PDNEC were histologically identical to the oat cell type carcinoma of the bronchus and were associated with an extremely aggressive clinical course with both patients dying of widespread metastases within one month of registration. MDNEC also metastasized frequently with four of seven cases dying with widespread disease. The tumours have previously been reported as not being radiosensitive; however three cases remain free of disease following biopsy and radiotherapy alone. The place of radiotherapy in the management of these tumours is discussed.

Olfactory neural tumours—the role of external beam radiotherapy

Olfactory neuroblastoma is an uncommon tumour arising in the nasal cavity or paranasal sinuses. We report the management of nine cases treated with external beam radiotherapy subsequent to surgery, either attempted definitive removal or biopsy only. Recent refinements in pathological evaluation of these tumours are discussed. Seven cases were deemed classical olfactory neuroblastoma whilst two were classified as neuroendocrine carcinoma. The clinical features, radiotherapy technique and variable natural history are presented. Seven of eight patients treated radically were controlled locally, with a minimum follow-up of two years. Three patients developed cervical lymph node disease and three patients died of systemic metastatic disease. Suggestions are made as to which patients should have en-bloc resection rather than definitive radiotherapy.

Malignant melanoma with neuroendocrine differentiation: clinical, histological, immunohistochemical and ultrastructural features of three cases.

Aim : To document the clinical, histological, immunohistochemical and ultrastructural features of three malignant melanomas showing neuroendocrine differentiation.

Primary malignant lymphoma of the thyroid : a clinicopathological analysis

A retrospective analysis of 70 patients with primary malignant lymphoma of the thyroid treated at this institute between 1965-1983 has been conducted. The clinicopathological features and prognostic factors have been studied. The mean age was 67.5 years and there was a marked female:male ratio of 8:1. A total of 32 (45.7%) Stage IE and 38 (54.3%) Stage IIE patients were identified. In 64 cases histological material was reviewed and classified employing the Kiel classification. All the tumors were of B cell lineage and the majority were follicle center cell type. A biopsy only was performed in 27 patients, lobectomy in 11 patients, subtotal thyroidectomy in 27 and macroscopic thyroidectomy in 5 patients. All patients were treated with radiotherapy. The overall 5-year survival was 42%, with 63% for Stage IE and 27% for Stage IIE. The corrected overall 5-year survival was 49% with 68% for Stage IE and 36% for Stage IIE. The corresponding overall relapse free survival was 42% with 60% for Stage IE, and 31% for Stage IIE. Factors of prognostic significance for relapse and survival were stage, radiotherapy dose, stridor, retrosternal extension and fixation.

Post‐transplant T‐cell lymphoproliferative disorder/T‐cell lymphoma: a report of three cases of T‐anaplastic large‐cell lymphoma with cutaneous presentation and a review of the literature

Aims:  To report the clinical, pathological and immunohistochemical features of three cases of post‐transplant T‐cell lymphoproliferative disorder (T‐PTLD) T‐cell lymphoma with primary cutaneous presentation.

Malignant melanoma showing ganglioneuroblastic differentiation: report of a unique case.

We report a case of metastatic malignant melanoma in an inguinal lymph node, expressing ganglioneuroblastic differentiation. This was characterized by the presence of discrete nests and islands of large ganglion cells with abundant cytoplasm and eccentric nuclei with prominent nucleoli admixed with smaller primitive neuroblasts. The cells were separated by pale pink fibrillar material representing neuritic cell processes. These foci of ganglioneuroblastoma were seen over a background of an otherwise typical metastatic epithelioid, focally melanotic, malignant melanoma. Immunohistochemistry showed positivity for neurofilament, synaptophysin, chromogranin, vasoactive intestinal peptide, and glial fibrillary acidic protein in the areas with ganglioneuroblastic differentiation, but not in the melanocytic component. Conversely, HMB45 positivity was expressed by the melanocytic cells only. S-100 protein and Melan-A, a putative melanocytic marker, showed positivity in both melanocytic and ganglioneuroblastic components. Ultrastructurally, neuritic cell processes and dense core neurosecretory granules were identified in the ganglionic and neuroblastic cells. A subsequent nodal metastasis in the same region showed focal neuroblastic differentiation without the ganglionic element. No evidence of neuronal or ganglionic differentiation was seen in the primary skin melanoma.