Role of fine needle aspiration cytology in the diagnosis of a rare case of a poorly differentiated synovial sarcoma with “Rhabdoid” features,including treatment implications

Synovial sarcoma is a high‐grade, soft tissue sarcoma that is relatively chemosensitive. Its exact diagnosis is crucial, including differentiation from its closest diagnostic mimic, ie, Ewing sarcoma, in view of different treatment options, including chemotherapy regimens, for both these tumors. A 15‐year‐old girl presented with a recurrent soft tissue mass in her right popliteal region, which was diagnosed as Ewing sarcoma, based on positive immunoexpression of MIC2/CD99, Fli1 and negative expression of LCA and desmin. During her metastatic “work‐up”, a popliteal lymph node was identified, which was aspirated and examined. Fine needle aspiration cytology smears showed singly scattered and loose, cohesive clusters of cells containing round to polygonal, to short spindle‐shaped nuclei with prominent nuclei, and moderate to abundant cytoplasm, including several “rhabdoid” cells. These features prompted a review of the biopsy of the recurrent tumor, and additional immunohistochemical stains, which revealed positive co‐expression of pan cytokeratin (AE1/AE3), epithelial membrane antigen (EMA), along with a characteristic variable staining pattern of INI11/SMARCB1. Subsequently, by fluorescent in situ hybridization (FISH) technique, performed on the paraffin section of the recurrent tumor, 100% tumor nuclei displayed SS18 rearrangement, while none of the tumor cells displayed EWSR1 rearrangement. Diagnosis of poorly differentiated SS with “rhabdoid” features was confirmed. This constitutes as the first case, describing cytopathologic features of a poorly differentiated SS with “rhabdoid” features, initially misdiagnosed as a Ewing sarcoma, on biopsy and confirmed as SS by FISH technique. The diagnostic and treatment implications in this case are discussed herewith. Diagn. Cytopathol. 2017;45:662–667. © 2017 Wiley Periodicals, Inc.     

Urothelial carcinoma of the renal pelvis with rhabdoid features

Reported herein is the case of a 70-year-old man with high grade urothelial carcinoma (UC) with rhabdoid features of the renal pelvis. For the most part, the tumor was composed of pleomorphic, non-cohesive round tumor cells with abundant cytoplasm. In situ high-grade UC composed of cohesive tumor cells was seen only in a small portion. Pleomorphic dyscohesive tumor cells often showed rhabdoid features, containing eosinophilic inclusions. These pleomorphic/rhabdoid tumor cells were immunohistochemically positive for vimentin but negative for cytokeratins, CD45, CD20, CD79a, CD3, CD45RO, CD38, and CD138. Loss of heterozygosity (LOH) analysis demonstrated identical allelic losses as well as additional allelic losses for the dyscohesive and cohesive UC lesion, indicating that these two lesions originated from a single clonal lesion.     

Epithelioid angiosarcoma of the kidney: a diagnostic dilemma in fine-needle aspiration cytology

Epithelioid angiosarcomas (EAS) of kidney are rare and aggressive tumors with noncharacteristic imaging features that overlap with those of inflammatory conditions and renal cell carcinoma (RCC). We report the fine-needle aspiration (FNA) cytology findings of a case of EAS that involved the left kidney of an 83-year-old male. The smears and cell block sections showed pleomorphic epithelioid cells with ample cytoplasm, eccentric nuclei, occasional cytoplasmic hyaline globules, and rare intracytoplasmic lumina. Immunohistochemical stains performed on cellblock sections showed that the tumor cells were positive for vimentin, CD31, CD34, Factor VIII, and CD10, but showed no staining for cytokeratins AE1/AE3 and 8/18, HMB45, CD45, smooth muscle actin, and S100. The morphological and immunohistochemical distinction between EAS, primary tumors of the kidney, and other epithelioid and rhabdoid neoplasms is discussed.     

Aspiration cytology of primary thyroid paraganglioma

Thyroid paragangliomas are extremely rare tumors arising from the inferior laryngeal paraganglia. Most patients are female and present as asymptomatic thyroid nodule. Diagnosing thyroid paraganglioma can be difficult on fine‐needle aspiration (FNA) since it could be misdiagnosed as medullary thyroid carcinoma, calcitonin‐negative neuroendocrine tumor of the thyroid gland (CNNETT), metastatic neuroendocrine tumor, and intrathyroid parathyroid proliferation. We describe the cytologic features and immunohistochemical staining pattern of thyroid paraganglioma from a 60‐year‐old woman with a gradually enlarging neck mass for several months. An ultrasound guided fine‐needle aspiration was performed which revealed epithelioid, plasmacytoid to occasionally spindle‐shaped cells with ovoid to elongated nuclei, fine chromatin pattern and inconspicuous nucleoli. The cells were arranged singly, in sheets, and focally in acinar pattern. Occasional nuclear overlapping, crush artifact, and binucleated cells were identified. Neither colloid nor amyloid was seen. Immunohistochemical stains performed on the cell block showed the tumor cells were positive for neuroendocrine markers and negative for cytokeratin (AE1/AE3), calcitonin, CEA, thyroglobulin, and TTF‐1. There were rare S‐100 positive cells. Given the difference in management of paragangliomas compared to its cytology mimics and association with familial cancer syndromes in some cases, awareness of this rare tumor, and use of immunohistochemical stains are critical in arriving at the diagnosis. Diagn. Cytopathol. 2015;43:838–843. © 2015 Wiley Periodicals, Inc.     

Prostatic stromal sarcoma with rhabdoid features

Rhabdoid tumors have been reported in many different anatomic sites as an aggressive tumor and usually present with a rhabdoid tumor component (a composite tumor) rather than a pure rhabdoid tumor. Rhabdoid tumor in the prostate has been described only once in the prostatic region as a possible epithelial origin. Rhabdoid features in prostatic stromal sarcomas (PSSs) have never been described in the literature. Here, we report a case of a PSS with rhabdoid features. A 31-year-old man presented with a 4-month history of voiding difficulty and anal pain. Computed tomography of the abdomen revealed an ovoid mass in the prostate invading rectum and urinary bladder. A needle biopsy was diagnosed as an unclassified spindle cell sarcoma, and 2 cycles of adriamycin-based neoadjuvant chemotherapy were given, followed by radical prostatectomy. The prostatectomy specimen revealed a high-grade sarcoma with fascicles of highly cellular spindle cells and numerous mitoses with hemorrhage and necrosis. In areas, the tumor also contained sheets of loosely cohesive epithelioid cells with rhabdoid tumor component. Both spindle and rhabdoid tumor cells were positive for vimentin, CD34, and progesterone receptor and negative for desmin and cytokeratin immunostainings. The rhabdoid tumor cells retained INI1 expression. The tumor recurred in the bladder, and the patient died of sepsis. To the best of our knowledge, this is the first case of PSS with rhabdoid features. The tumor showed an aggressive clinical behavior with a short-term survival (7 months after diagnosis).     

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.     

Sarcomatoid carcinoma of the gallbladder with a rhabdoid tumor component

We report the case of a sarcomatoid carcinoma with a rhabdoid tumor component originating in the gallbladder, along with immunohistochemical and electron microscopic findings. A 61-year-old woman presented with a 5-month history of right upper quadrant pain. Ultrasonography and a computed tomographic scan indicated gallbladder cancer. She underwent a cholecystectomy and a common bile duct resection. A firm mass (4.5 cm in greatest dimension) was present in the neck portion of the gallbladder. The mass was firm, solid, yellowish gray, and granular with areas of necrosis. Microscopically, the tumor was a biphasic sarcomatoid carcinoma and consisted of diffusely arranged pleomorphic cells, focally showing rhabdoid features and neoplastic glands with focal mucin production. Heterologous components such as osteoid, chondroid, and rhabdomyoblastic elements were not identified. By immunohistochemical staining, we demonstrated that the rhabdoid cells coexpressed cytokeratin and vimentin. On electron microscopic examination, the rhabdoid tumor cells showed cytoplasmic whorls of intermediate filaments in the cytoplasm and eccentric nuclei. Two months postoperatively, the follow-up computed tomographic scan showed multiple intrahepatic metastases and omental seedings.     

CD44‐expressing undifferentiated carcinoma with rhabdoid features of the pancreas: Molecular analysis of aggressive invasion and metastasis

Carcinoma with rhabdoid features is a rare malignant tumor with a poor prognosis whose molecular mechanism for aggressive behavior is unclear. We describe an undifferentiated pancreatic carcinoma with rhabdoid features that demonstrated extensive invasion and metastasis. Examination of a 63‐year‐old man with back pain disclosed a retroperitoneal tumor with multiple metastases. Lymph node biopsy revealed an undifferentiated carcinoma of unknown origin. Intensive chemotherapy was ineffective; the patient died 3 months after initial symptoms. Autopsy showed that the tumor displaced the retroperitoneal space: it diffusely invaded and destroyed the pancreas and duodenum. Histology demonstrated tumor cells with eccentric vesicular nuclei, large nucleoli, juxtanuclear eosinophilic inclusions, and poor cell adhesion. Immunohistochemistry showed that tumor cells expressed cytokeratin and vimentin, and electron microscopy confirmed a perinuclear mass of intermediate fibrils and lipid droplets, which indicated an undifferentiated carcinoma with rhabdoid features. Tumor tissue contained hyaluronan; tumor cells strongly expressed CD44, matrix metalloproteinase‐9, hypoxia‐inducible factor‐1α, hyaluronan synthase 2, and acyl‐CoA:cholesterol acyltransferase 1 and had a high Ki‐67⁺ ratio. Since hyaluronan is a ligand for CD44, formation of CD44‐hyaluronan complex on the cell surface activates CD44 and this activation may explain why the tumor manifested aggressive invasion and metastasis throughout the clinical course.     

Malignant melanoma with a rhabdoid phenotype: histologic, immunohistochemical, and ultrastructural study of a case and review of the literature

Malignant melanoma is known to display tremendous histologic diversity. One rare variant is the rhabdoid phenotype, so called because of the appearance of cells resembling rhabdomyoblasts seen in malignant rhabdoid tumors of the kidney. We present the histologic, immunohistochemical, and ultrastructural features of a malignant melanoma composed entirely of rhabdoid cells. A 62-year-old man presented with a 6.5-cm lung mass. Although presumed to be a metastatic lesion, extensive workup failed to reveal a primary tumor site. Histologic sections showed a mass composed entirely of polygonal neoplastic cells with prominent nucleoli and large hyaline cytoplasmic inclusions. The tumor cells were strongly immunoreactive with S100 protein, vimentin, and CD56, and were focally reactive with Mart-1. Tumor cells were negative for Melan-A, tyrosinase, HMB-45, AE1/AE3, cytokeratin (CK) 7, CK8/ 18, CK20, CK903, CAM 5.2, epithelial membrane antigen, smooth muscle actin, desmin, leukocyte common antigen, Bcl-2, CD3, CD20, CD30, CD138, kappa and lambda light chains, CD68, CD34, factor VIII, synaptophysin, and glial fibrillary acidic protein. Electron microscopy showed cytoplasmic whorls of intermediate filaments containing entrapped rough endoplasmic reticulum, mitochondria, and lipid. Recognition of this rare variant of malignant melanoma is important in the evaluation of tumors with rhabdoid morphology.     

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.     

Rhabdoid cholangiocarcinoma: a variant of cholangiocarcinoma with aggressive behavior

A rhabdoid cholangiocarcinoma is a very rare variant of sarcomatous cholangiocarcinomas. Here, we report a vimentin positive cholangiocarcinoma showing rhabdoid features in the entire tumor, with a very aggressive behavior. A 41-year-old woman was admitted to our hospital due to a huge hepatic mass. The resected liver revealed a 17 x 15 cm sized solid mass with extensive necrosis and an infiltrative border. On microscopic examination, the entire tumor was composed of loosely cohesive round to polygonal cells, with rhabdoid features having abundant eosinophilic glassy cytoplasm and eccentrically located vesicular nuclei. Some tumor cells contained intracytoplasmic mucin vacuoles, but definite areas of glandular differentiation or spindle cell were not found. Immunohistochemical staining showed a diffuse strong positive reaction to pan-cytokeratin and vimentin, and focal positivity for the carcinoembryonic antigen. Other immunohistochemical stainings for cytokeratin 7, cytokeratin 20, S-100 protein, HMB-45, desmin, alpha-smooth muscle actin, c-kit, CD34, alpha-fetoprotein, anti-hepatocyte antigen, chromogranin and synaptophysin were all negative. After two months, the patient developed a local recurrence along the resection margin, and multiple hematogenous metastases to the lung and liver were seen on the follow-up CT scan.     

Histiocytic sarcoma of the parotid gland region

Histiocytic sarcoma (HS) is a malignant neoplasm showing the morphological and immunophenotypic features of mature histiocytes. Reported herein is a case of HS of the parotid gland region. A 53-year-old woman noticed a swelling of the right preauricular area. Preoperative fine needle aspiration cytology showed an admixture of pleomorphic atypical cells and mature lymphocytes. She underwent total parotidectomy. Grossly, the tumor was located at the parotid gland to subcutaneous tissue, and showed infiltrative growth with massive necrosis and hemorrhage. Microscopically, the tumor was composed of marked pleomorphic cells with eosinophilic cytoplasm. Bizarre multinuclear giant cells were scattered and intermingled. Tumor cells were positive for CD68 (KP-1 and PG-M1), CD163, S-100 protein, CD1a, CD4 and CD31, but negative for CD3, CD20, CD21, CD79a, DEC205 and langerin, immunohistochemically. Monoclonal proliferation of B cells was not confirmed on polymerase chain reaction for IgH. The patient had recurrent lesions in the pelvis and stomach 5 months after parotidectomy and died of the disease 10 months after the operation.     

Metastatic pheochromocytoma to the pancreas diagnosed by endoscopic ultrasound‐guided fine needle aspiration: A case report and review of literature

Pancreatic pheochromocytomas are rare and typically diagnosed by local resection. We present the first reported case of metastatic pheochromocytoma to the pancreas diagnosed by endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) and cytology. A 67‐year‐old female presented with 2 to 3 months of abdominal pain. A CT scan showed a large mass in the head of the pancreas engulfing the superior mesentery artery and vein, along with a large mass in the left adrenal gland. An EUS‐FNA was performed on the pancreatic mass with a 22‐gauge needle, yielding an adequate sample. Papanicolaou stain, Diff‐Quik, and cell block showed loosely cohesive clustered tumor cells and singly dispersed pleomorphic naked tumor nuclei with anisonucleosis and cytoplasmic vacuolization. Tumor cells stained positive for synaptophysin, chromogranin A, and CD56 and negative for CK AE1/3 and CK AE1/3‐CAM5.2 cytokeratin cocktail. Because of cytokeratin negativity, diffusely positive neuroendocrine markers, and the presence of an adrenal mass, a metastatic malignant pheochromocytoma was suspected. Additional testing showed elevations in plasma metanephrines and normetanephrines, urine metanephrine‐to‐creatinine and normetanephrine‐to‐creatinine ratios, and serum chromogranin A. An iodine¹²³‐metaiodobenzylguanidine (MIBG) scan was obtained, which showed significantly increased MIBG uptake in the left adrenal lesion. A diagnosis of metastatic malignant pheochromocytoma was made. Surgical oncology was consulted, who recommended against resection of the adrenal mass in favor of outpatient management. Metastatic pheochromocytoma to the pancreas are rare tumors that may yield diagnostic material by EUS‐FNA with a 22‐gauge needle.     

Low-grade malignant perineurioma (perineurial sarcoma) of soft tissue: a potential diagnostic pitfall on fine needle aspiration

A case of low-grade malignant perineurioma presenting as a mass in the thigh is described. The patient was a 76-year-old woman with an enlarging painful mass on her right lateral thigh over the past 2 months. Thorough clinical and radiological studies did not reveal any evidence of tumor elsewhere. The patient underwent fine needle aspiration of the mass, which revealed pleomorphic spindle cells in small clusters or dispersed as single cells within myxoid stroma, cytologically consistent with a high-grade sarcoma. At surgery, the tumor was found to be entirely confined within the muscle. Grossly, the tumor measured 6.5 cm in greatest diameter and showed a gray-white fleshy cut surface that was well circumscribed but unencapsulated. Histologic examination showed a highly cellular spindle cell proliferation embedded within myxoid stroma. The tumor cells showed mild to moderate nuclear pleomorphism with minimal mitotic activity. No evidence of hemorrhage or necrosis was noted. The tumor irregularly invaded the surrounding skeletal muscle. Immunohistochemical studies showed weak membranous positivity for epithelial membrane antigen and focal cytoplasmic positivity for CD34; stains for smooth muscle actin, cytokeratin AE1/AE3, desmin, CD56, H-caldesmon, calponin, and S-100 protein were negative. Electron microscopy showed cells with thin, elongated cytoplasmic processes extending along connective tissue in a parallel, onion-like arrangement and prominent subplasmalemmal pinocytotic activity. The marked pleomorphism displayed on fine needle aspiration observed in this case can lead to a mistaken diagnosis of high-grade sarcoma resulting in unnecessarily aggressive management.     

Adrenocortical adenoma with rhabdoid features

We report a case of an aldosterone producing adrenocortical adenoma with rhabdoid features in a 16-year-old girl. Grossly, the tumor measured 30 mm in diameter and weighed 24 g. Histologically, the tumor was composed of approximately equal parts of tumor cells with rhabdoid features arranged in a solid and trabecular pattern and cells characterized by compact eosinophilic cytoplasm, solid growth with focal necroses, and increased mitotic activity. The lipid-rich tumor cells with ample clear vacuolized cytoplasm represent a minor component. Immunohistochemically, all the tumor cells showed the same results and were positive for vimentin, synaptophysin, Melan A, and alpha-inhibin. Cytokeratin CAM 5.2 was positive only focally. Chromogranin A, actin, alpha-actin, S100 protein, EMA, and cytokeratin AE1/AE3 were negative. Rhabdoid features have been described in many tumors of variable histogenesis; however, to the best of our knowledge, the presence of rhabdoid phenotype has never been described in either adrenocortical adenoma or carcinoma.     

Spectrum of cytopathologic features of epithelioid sarcoma in a series of 7 uncommon cases with immunohistochemical results,including loss of INI1/SMARCB1 in two test cases

Diagnosis of an epithelioid sarcoma (ES) is challenging on fine needle aspiration cytology (FNAC) smears. There are few documented series describing cytopathologic features and immunostaining results of ESs. The present study describes cytopathologic features of seven cases of ES. All seven tumors occurred in males within age‐range of 22–61 years; in sites, such as forearm (n = 3), hand (n = 2), thigh (n = 1), and inguinal region (n = 1). FNAC was performed for metastatic lesions (n = 5), recurrent lesions (n = 4), as well as for a primary diagnosis (n = 1). FNAC smears in most cases were moderate to hypercellular, composed of polygonal cells(seven cases) and spindle cells(three cases), arranged in loosely cohesive groups, non‐overlapping clusters, and scattered singly, containing moderate to abundant cytoplasm, defined cell borders, vesicular nuclei, and discernible nucleoli. Variable cytopathologic features identified in certain cases were “rhabdoid‐like” intracytoplasmic inclusions (n = 5), giant cells (n = 3), and interspersed scanty, metachromatic stroma (n = 4). Histopathologic examination revealed two cases of conventional‐type ES, three of proximal/large cell‐type ES, and two cases of mixed‐type ES, displaying features of conventional and proximal subtypes. By immunohistochemistry (IHC), tumor cells were positive for cytokeratin (CK)(4/5), epithelial membrane antigen (EMA) (6/6), panCK (1/1), vimentin (3/3), and CD34 (7/7). Tumor cells were completely negative for INI1/SMARCB1 (0/2) and CD31 (0/5). In our settings, FNAC was mostly performed in recurrent and/or metastatic cases of ES, and rarely for a primary diagnosis of ES. Important cytopathologic features of ESs include loosely cohesive, non‐overlapping clusters of polygonal cells with variable “rhabdoid‐like” and spindle cells. Optimal diagnostic IHC markers in such cases include CK, EMA, AE1AE3, CD34, and INI1/SMARCB1. Clinical correlation is imperative in all cases. Diagn. Cytopathol. 2016;44:636–642. © 2016 Wiley Periodicals, Inc.