Melanotic medullary thyroid carcinoma: A case report with review of the literature

Melanotic medullary thyroid carcinoma is morphologically defined by the presence of melanin deposits in the cytoplasm of tumor cells. It is an extremely rare variant with only 15 cases described in the literature to date and only one report of diagnosis by fine needle aspiration (FNA) biopsy. A 51-year-old woman presented with neck swelling. An ultrasound examination revealed a single solid nodule in the right thyroid lobe that measured 5.4 × 4.7 × 4.3 cm. Laboratory examination revealed elevated levels of serum calcitonin (8643.0 pg/ml), carcinoembryonic antigen (CEA) (86.2 ng/ml), and chromogranin A (123.2 ng/ml). An FNA biopsy of the thyroid nodule revealed predominantly single plasmacytoid cells with round to oval eccentric nuclei and dark brown intracytoplasmic granules. Immunohistochemical studies with Melan-A performed on a cell block slide confirmed that the granules contained melanin. The tumor cells were also positive for calcitonin, CEA, synaptophysin, AE1/AE3, CAM5.2, and HMB-45(focal); the tumor cells were negative for chromogranin, thyroglobulin, PAX8 and TTF-1. The diagnosis was reported as melanotic variant of medullary thyroid carcinoma. The patient underwent a total thyroidectomy which revealed tumor cell expression of insulinoma-associated protein 1 and confirmed neuroendocrine differentiation. Shortly after she presented with tumor recurrence in the thyroidectomy bed. The tumor cells were positive for only S100, SOX10, and Melan-A. Molecular analysis with the SEMA4 Solid Tumor Panel revealed mutations in the HRAS, PIK3CA, PIK3R1, MYC, and CCND3 genes. The final diagnosis was reported as melanocytic medullary thyroid carcinoma with high grade transformation and loss of epithelial and neuroendocrine expression.     

Adenomatoid tumour of the liver

An unusual primary adenomatoid tumour arising in the normal liver is described. Hepatectomy was performed, and the patient is alive and free of disease 1 year postsurgery. Grossly, the tumour showed a haemorrhagic cut surface with numerous microcystic structures. Histological examination revealed cystic or angiomatoid spaces of various sizes lined by cuboidal, low-columnar, or flattened epithelioid cells with vacuolated cytoplasm and round to oval nuclei. The epithelioid cells were entirely supported by proliferated capillaries and arteries together with collagenous stroma. Immunohistochemical studies showed that the epithelioid cells were strongly positive for a broad spectrum of cytokeratins (AE1/AE3, CAM5.2, epithelial membrane antigen and cytokeratin 7) and mesothelial markers (calretinin, Wilms' tumour 1 and D2-40). These cells were negative for Hep par-1, carcinoembryonic antigen, neural cell adhesion molecule, CD34, CD31 and HMB45. Atypically, abundant capillaries were observed; however, the cystic proliferation of epithelioid cells with vacuoles and immunohistochemical profile of the epithelioid element were consistent with hepatic adenomatoid tumour.     

Ossifying fibromyxoid tumor: Report of a case with cytomorphologic description

Ossifying fibromyxoid tumor (OFMT) is a rare soft tissue neoplasm with uncertain histogenesis. Most cases behave in a clinically benign fashion; however, a small percentage of tumors may locally recur or metastasize. Herein we present a case of a 56‐year‐old man who presented with an enlarging left groin mass, left inner thigh numbness, burning paresthesia and discomfort in his left groin. The mass sampled by fine‐ needle aspiration and needle core biopsy. Cytology showed bland‐appearing epithelioid cells with round nuclei and fine chromatin, with fragments of fibromyxoid stroma in the background. Immunohistochemical stains performed on the core biopsy showed that the lesional cells were focally positive for S100 protein and negative for desmin, smooth muscle actin, CD34 and cytokeratin AE1/AE3. A benign neoplasm was favored with ossifying fibromyxoid tumor as the main entity in the differential diagnosis. A subsequent resection showed a well‐circumscribed 5 cm mass with firm consistency and focal areas of calcifications. Histologically, the tumor had a nodular growth pattern with relatively bland spindle cells containing round to oval nuclei suspended in a variably collagenous to myxoid stroma. Significant ossification and bone formation was also noted. There was no significant atypia, necrosis or increased mitoses. Ossifying fibromyxoid tumors have distinct cytologic features and should be considered in the differential diagnosis of soft tissue tumors with prominent ossification. Diagn. Cytopathol. 2015;43:646–649. © 2015 Wiley Periodicals, Inc.     

Myxoid epithelioid gastrointestinal stromal tumor (GIST) with mast cell infiltrations: a subtype of GIST with mutations of platelet-derived growth factor receptor alpha gene

We analyzed 30 gastrointestinal stromal tumors (GISTs) that were immunohistochemically weak or negative for KIT. Histologically, all 30 GISTs consisted of epithelioid tumor cells in at least a part of the tumor. The tumor cells showed different morphologies and arranged themselves in different histological patterns. In 20 of the 30 GISTs, round or oval epithelioid tumor cells often showed a less cohesive pattern of growth and showed eosinophilic cytoplasm and peripherally placed nuclei with myxoid stroma, whereas in the remaining 10 cases, tumor cells were arranged in a more cohesive pattern without myxoid stroma. The former type of tumors is called myxoid epithelioid GISTs in this study. Subsequent mutational analyses showed that the platelet-derived growth factor receptor alpha (PDGFRA) gene mutations in exon 12 or exon 18 were identified in 20 (66.7%) of the 30 GISTs, and especially in 18 (90%) of the 20 myxoid epithelioid GISTs. Moreover, 17 (85%) of the 20 myxoid epithelioid GISTs were accompanied by mast cell infiltrations within the tumor nodules. In the remaining cases, 2 (6.7%) of the 30 GISTs had c-kit gene mutations in exon 11, and no mutation was found in 8 (26.7%) of 30 GISTs. None of the patients with myxoid epithelioid GISTs died of disease. These results suggest that myxoid epithelioid GISTs are a distinct subtype of GISTs that are closely correlated with the PDGFRA gene mutation and that recognition of such histological characteristics should be helpful for molecular subclassification of GISTs that are important for molecular targeting therapy by imatinib mesylate (STI571).     

The amyloid deposit in calcifying epithelial odontogenic tumor is immunoreactive for cytokeratins

Calcifying epithelial odontogenic tumor, also known as Pindborg tumor, is a rare benign tumor with locally aggressive behavior. It is characterized by squamous epithelial cells, calcifications, and eosinophilic deposits that have been identified as amyloid. We report a case of calcifying epithelial odontogenic tumor and investigate the nature of the amyloid, using histologic, immunohistochemical, and ultrastructural studies. The amyloid was immunohistochemically negative for basement membrane components and positive for all cytokeratin stains performed (cocktail of cytokeratins 1, 5, 6, 8, 13, and 16, and cytokeratins AE1 and AE3). The amyloid stained focally in a glandular-like pattern, reminiscent of the epithelial glandlike structures of the tumor. We conclude that the amyloid is derived from filamentous degeneration of keratin filaments that originate from the tumor squamous epithelium. The keratin degeneration is part of a developmental or aging process that the tumor undergoes.     

Parachordoma or chordoma periphericum? Case report of a tumor of the thoracic wall

We report the findings from an aspiration biopsy and resection of a chordoma-like tumorous mass in the wall of the thorax of a 36-yr-old man with immunohistochemical, ultrastructural, and cytogenetic studies. The 4-cm oval tumor was an incidental finding on physical examination, and no other lesions were identified after comprehensive radiologic studies. The aspirate was composed of sheets and nests of cells with distinct borders in a myxoid and fibrillary extracellular matrix. The neoplastic cells were uniform and round or polygonal with abundant pale blue vacuolated cytoplasm and small round, central or eccentric nuclei. On electron microscopy, mitochondrial rough endoplasmic reticulum complexes were seen in neoplastic cells. These features were similar to those of a conventional chordoma. However, the cytogenetic pattern, 43, XY ,-1, -2, der (5)t(1p;5q), -6, add(8p) ,add(10q), was not typical. In addition, the neoplastic cells were positive for vimentin, S-100, AE1/AE3, CAM 5.2, and CK 19; were focally positive for EMA and smooth muscle actin; and were negative for cytokeratin 1 and 10 (34 beta E12), CK 7, CK 8 (35H 11B), CK 17, and CK 20. The cytogenetic and immunohistochemical patterns were different from conventional chordoma and its peripheral counterpart, chordoma periphericum, suggesting the diagnosis of parachordoma. To the best of our knowledge, this is the first report of fine-needle aspiration of this newly defined and rare entity.     

Small cell carcinoma of the urinary bladder

Primary small cell carcinoma of the urinary bladder is very rare; only several studies have been reported in the English literature. A 62-year-old woman was admitted to our hospital because of hematuria and dysuria. Bladder endoscopy revealed a large polypoid tumor at the bladder base. Transurethral bladder tumorectomy (TUR-BT) was performed. Many TUR-BT specimens were obtained. Histologically, the bladder tumor was pure small cell carcinoma. Immunohistochemically, the tumor cells were positive for cytokeratin (CK) AE1/3, CK CAM5.2, CK8, CK18, neurone-specific enolase, chromogranin, NCAM (CD56), synaptophysin, Ki-67 (labeling=100%), p53, KIT (CD117), and platelet-derived growth factor receptor-α (PDGFRA). The tumor cells were negative for CK5/6, CK 34BE12, CK7, CK14, CK19, CK20, p63, CD45, and TTF-1. A molecular genetic analysis using PCR-direct sequencing showed no mutations of KIT (exons 9, 11, 13 and 17) and PDGFRA (exons 12 and 18) genes. No metastases were found by various imaging techniques. The patient is now treated by cisplatin-based chemotherapy.     

Pulmonary synovial sarcoma with polypoid endobronchial growth: a case report, immunohistochemical and cytogenetic study

A rare case of primary pulmonary synovial sarcoma with polypoid endobronchial growth in a 42-year-old Japanese woman is described. Left upper sleeve lobectomy was performed for the polypoid tumor measuring 2.5 cm in the left major bronchus and the patient was treated with adjuvant chemotherapy. Three years later, a recurrent tumor was discovered. Microscopically, this tumor was characterized by a proliferation of oval to spindle-shaped cells arranged in sheets and fascicles and covered by the thin normal bronchial epithelium. Immunohistochemically, tumor cells were positive for vimentin, and focally positive for pancytokeratin recognized by AE1/AE3, cytokeratin 7 and epithelial membrane antigen. A chimera gene, SYT-SSX1, was detected. Recently, primary pulmonary synovial sarcoma is an increasingly recognized clinical entity; however, most of these tumors present as a parenchymal mass. The present case is a unique example of primary synovial sarcoma of endobronchial polypoid type. This case suggests that pulmonary synovial sarcoma might originate from bronchial submucosal stromal tissue.     

Intra-epithelial neuroendocrine carcinoma of the nasal cavity

We describe a distinctive neuroendocrine carcinoma (NEC) that proliferated intra-epithelially. The tumor was 35 mm in diameter and arose from the right superior turbinate of a 46-year-old woman. Histologically, the tumor exhibited papillary growth and the tumor cells were localized in the thickened mucosal epithelium. The tumor cells had round to oval and vesicular or hyperchromatic nuclei, and cohered without any specific structure such as a fibrillary background, rosette or glandular structure. No stromal invasion by the tumor was observed. Immunohistochemically, the tumor cells were positive for neuron-specific enolase focally. In addition, many tumor cells expressed cytokeratin (AE1/AE3 and CAM 5.2), mostly with characteristic perinuclear dot-like patterns. Electron microscopy revealed focal but well-eveloped cytoplasmic processes containing arrays of microtubules and a few dense core granules. The tumor was considered to be a poorly differentiated neuroendocrine carcinomas (NEC) that exhibited exceptional intra-epithelial proliferation. The tumor completely disappeared after the stereotactic radiosurgery and has not recurred for 40 months. It might be difficult to distinguish a poorly differentiated NEC in the sinonasal region from other neuroectodermal tumors, including olfactory neuroblastoma, but the differential diagnosis is important because each tumor has different clinicopathological characteristics.     

Intra-abdominal desmoplastic small-cell tumor of the peritoneum

The authors described three cases of intraabdominal desmoplastic small round cell tumour of the peritoneum (IDSRT). In one case the patient was a woman, and in the other two men. The age ranged from 20-29 years. Common of all the cases was a rapid onset of clinical symptoms during the period of twelve to eighteen months. In one case, a 22-year-old woman presented with a symptomless course of disease documented by medical examination one month ago. Intensive chemotherapy was applied but two patients died of generalisation. The 22-year-old woman is alive but with clinical evidence of generalisation in the abdominal cavity. The "classical" type of IDSRT was found in all the cases. Sharply demarcated groups of tumour cells of different size were surrounded by dense fibrous stroma. In some regions desmoplastic areas prevailed. In one case the tumour consisted of round and oval cells resembling a lymphoma. In the other two cases, the slightly elongated cells were present. Immunohistologically, the small round cells were positive for cytokeratins with antibody AE1-AE3. Membrane and dot-like paranuclear positivity were found. In 2 cases the reaction to desmin was seen in a dot-like paranuclear distribution, whereas the reaction to smooth muscle actin (MSA) was negative. In all the cases positivity to vimentin and neuron specific enolase (NSE) were apparent. Negative reactions were found for WT-1 antibody in all three cases. In one of the cases the RT PCR reaction for chimeric gene EWS/WT1 was performed, and found to be negative. Many different tumour types, such as lymphoma, Ewing sarcoma/PNET, neuroblastoma, alveolar rhabdomyosarcoma, malignant mesothelioma must be excluded. Cytogenetic examination should be performed on tumours with a "non-typical" histological pattern and uncommon immunohistological examinations.     

Serous microcystic adenoma of the pancreas: cytologic and histologic features

Cytologic and histologic features in a case of serous microcystic adenoma of the pancreas in a 61-year-old female are presented. In fine-needle aspiration materials, epithelial cells arranged singly, in small clusters and in monolayer sheets were found. The neoplastic cells had round to oval nuclei with finely distributed chromatin and inconspicuous nucleoli. Nuclear atypia and mitoses were not seen. The cytoplasm was moderately abundant and finely granular. Histologically, the encapsulated tumor was composed of multiple small cysts lined by a single layer of flat to cuboidal cells. The tumor cells contained clear cytoplasm with glycogen and centrally located round to oval nuclei with inconspicuous nucleoli without any atypia. Mitoses were absent. The intervening stromal septa were hypocellular. Immunohistochemically, the tumor cells revealed diffuse positivity of cytokeratins and epithelial membrane antigen. Proliferative antigen Ki-67 was positive only in sporadic cells. No immunoreactivity for vimentin, carcinoembryonal antigen and S-100 protein was found. Chromogranin A and synaptophysin were expressed only in Langerhans' islets in the tumor capsula. In differential diagnosis, it is important to distinguish serous microcystic adenoma mainly from lymphangioma, cavernous hemangioma, serous cystadenocarcinoma, mucinous cystadenoma or cystadenocarcinoma, solid and pseudopapillary epithelial tumour, acinar cell cystadenocarcinoma, renal cell carcinoma and mesothelioma.     

Middle ear adenoma is an amphicrine tumor: why call it adenoma?

Middle ear adenoma (MEA) is a rare tumor postulated to take origin from the lining epithelium of the middle ear cavity. The authors report on a case of MEA arising in a 53-year old woman suffering from a sensation of fullness in her left ear, otalgia, and light left-sided hearing loss. Histopathologically, the lesion was composed of cuboidal and polygonal cells displaying a trabecular, tubulo-glandular, and solid pattern of growth. Immunohistochemically, neoplastic cells diffusely stained with anti-vimentin antibodies and were focally positive for chromogranin A, neuron-specific enolase, lysozyme, and cytokeratins AE1/AE3. The majority of tumor cells showed weak and diffuse staining with both anti-PP and anti-ACTH antibodies and intense positivity with anti-glucagon and anti Leu-7 antibodies. Ultrastructural investigation revealed both mucinous-glandular and neuroendocrine differentiation. The authors suggest that the appropriate terminology would be adeno-carcinoid or amphicrine tumor of the middle ear rather than "adenoma," a term that does not reflect its dual nature.     

Malignant Mesothelioma with Intracytoplasmic Crystalline Inclusions

Middle ear adenoma (MEA) is a rare tumor postulated to take origin from the lining epithelium of the middle ear cavity. The authors report on a case of MEA arising in a 53-year old woman suffering from a sensation of fullness in her left ear, otalgia, and light left-sided hearing loss. Histopathologically, the lesion was composed of cuboidal and polygonal cells displaying a trabecular, tubulo-glandular, and solid pattern of growth. Immunohistochemically, neoplastic cells diffusely stained with anti-vimentin antibodies and were focally positive for chromogranin A, neuron-specific enolase, lysozyme, and cytokeratins AE1/AE3. The majority of tumor cells showed weak and diffuse staining with both anti-PP and anti-ACTH antibodies and intense positivity with anti-glucagon and anti Leu-7 antibodies. Ultrastructural investigation revealed both mucinous-glandular and neuroendocrine differentiation. The authors suggest that the appropriate terminology would be adeno-carcinoid or amphicrine tumor of the middle ear rather than "adenoma," a term that does not reflect its dual nature.     

Participation of liver cancer stem/progenitor cells in tumorigenesis of scirrhous hepatocellular carcinoma--human and cell culture study

Cancer stem cells reportedly participate in the tumorigenesis of some neoplasms. Scirrhous hepatocellular carcinoma is a variant of hepatocellular carcinoma with abundant fibrous stroma. Herein, we clinicopathologically examined scirrhous (29 cases) and conventional (50 cases) hepatocellular carcinoma with reference to cancer stem cells. Scirrhous hepatocellular carcinoma was classifiable into 3 types based on small neoplastic cells at the periphery of tumor cell nests. Of 29 cases of scirrhous hepatocellular carcinoma, 21 contained small neoplastic cells. Immunohistochemically, those cells were positive for cytokeratin 7 and ATP-binding cassette transporter G2. In 11 cases, those small tumor cells were also positive for cytokeratin 19, neural cell adhesion molecule, and epithelial cell adhesion molecule (type 1), whereas 10 cases did not show such additional expression (type 2). The remaining 8 tumors did not contain small tumor cells with stem cell features (type 3). In the central parts of tumor nests, carcinoma cells got hepatocellular markers and lost expression of neural cell adhesion molecule, and epithelial cell adhesion molecule, suggesting hepatocellular maturation. Transforming growth factor beta1, a fibrogenic cytokine, was also detected in those small tumor cells. Culture cells extracted as "side population" from hepatocellular carcinoma cell lines (HuH7 and PLC5) expressed more intensely cytokeratins 7 and 19, neural cell adhesion molecule, epithelial cell adhesion molecule, and transforming growth factor beta1 than did non-side population cells. Small tumor cells with stem cell features in scirrhous hepatocellular carcinoma may correspond to side population of culture cells and might be involved in fibrogenesis of scirrhous hepatocellular carcinoma.