Malignant rhabdoid tumor of the uterus: Report of a case with findings in a cervical smear

Rhabdoid tumors are an uncommon group of neoplasms which share a distinctive morphology. We report the cytologic and histologic findings of a uterine rhabdoid tumor. The presence of rhabdoid cells on a cervical Papanicolaou (Pap) smear raises an intriguing differential diagnosis. Cytologists should be aware of this entity and consider rhabdoid tumor in the differential diagnosis when single malignant cells are noted on cervical Pap smear. © 1994 Wiley-Liss, Inc.     

Rhabdoid meningioma: Rapid intraoperative diagnosis on squash smears

Rhabdoid morphology in tumors refers to resemblance of the cells to rhabdomyoblasts without true skeletal muscle differentiation. The cytological features include abundant eosinophilic cytoplasm, eccentric nuclei, and intracytoplasmic hyaline inclusions. Besides the rhabdoid morphology, cytoarchitectural features of atypical meningioma (four or more mitoses per 10 high‐power fields, high cellularity, sheeting architecture, nuclear atypia, and necrosis) are seen in most cases. A case is presented here to highlight the appearance of rhabdoid cells on intraoperative squash smears, for most accurate treatment and close follow‐up, as rhabdoid morphology is related to aggressive behavior and poor outcomes. Diagn. Cytopathol. 2010;38:594–596. 2009 Wiley‐Liss, Inc.     

Rhabdoid meningioma: cytopathologic findings in cerebrospinal fluid

Rhabdoid meningioma is a recently described, rare, WHO Grade III intracranial tumor with an aggressive growth pattern and increased risk of recurrence. We describe the cytopathologic findings on cerebrospinal fluid of one such case in a 26-yr-old female who underwent resection of a left temporo-parietal mass. Cerebrospinal fluid contained abundant malignant cells with a prominent "rhabdoid" phenotype, i.e., large cells, eccentric nuclei, single prominent nucleoli, and dense eosinophilic cytoplasm. Although rhabdoid meningioma has a characteristic cytomorphology, the differential diagnosis of this tumor would involve metastatic adenocarcinoma, metastatic malignant melanoma, and other tumors with "rhabdoid" features (such as an atypical teratoid/rhabdoid tumor).     

Rhabdoid variant of urothelial carcinoma of the urinary bladder: a case report with emphasis on immunohistochemical analysis regarding the formation of rhabdoid morphology

Various histological variants of urothelial carcinoma (UC) have been described. They are associated with different clinical outcomes and/or therapeutic approaches; in addition, recognition of these histological variants is also important in preventing diagnostic misinterpretations. Histological variants based on cytoplasmic features, such as plasmacytoid, rhabdoid, clear-cell, and lipoid-rich variants, have been described in invasive UC. Herein, we report an exceedingly rare case of a rhabdoid variant of UC arising in the urinary bladder of a 61-year-old man. Including UC, the presence of rhabdoid cells has been described in various types of malignant tumors. These tumors are regarded as more aggressive neoplasms than those without rhabdoid cells. It has been previously found that non-degraded aggregation of intermediate filaments and membrane proteins conjugated with ubiquitin and p62 is a noticeable finding in the formation of rhabdoid morphology. We have validated the existence of this mechanism in a rhabdoid variant of UC by extensive immunohistochemical analysis.     

Adult renal cell carcinoma with rhabdoid morphology represents a neoplastic dedifferentiation analogous to sarcomatoid carcinoma

Renal cell carcinoma (RCC) with rhabdoid morphology (RCC-RM) is a recently described variant of RCC, which has an aggressive biologic behavior and poor prognosis, akin to sarcomatoid RCC. The current World Health Organization classification of RCC does not include the rhabdoid phenotype as a distinct histologic entity. The aim of this study is to investigate whether RCC-RM represents a dedifferentiation of a classifiable-type World Health Organization RCC or a carcinosarcoma with muscle differentiation. We reviewed 168 cases of RCC obtained between 2003 and 2008. From these cases, 10 (6%) were found to have areas of classic rhabdoid morphology. Immunohistochemistry for cytokeratin, epithelial membrane antigen, desmin, CD10, and CD117 was performed in each case using the labeled streptavidin-biotin method. Rhabdoid differentiation was identified in association with conventional-type RCC (9) and with unclassifiable-type RCC with spindle cell morphology (1). In all cases, both the rhabdoid and nonrhabdoid tumoral areas were positive for cytokeratin and epithelial membrane antigen and negative for desmin. Cytokeratin positivity in the rhabdoid areas was focal. In cases associated with conventional-type RCC, CD10 was positive in both the rhabdoid and nonrhabdoid foci. CD117 was negative in these tumors. The unclassifiable-type RCC with spindle cell morphology was negative for both CD10 and CD117. The similar immunophenotype between the rhabdoid and nonrhabdoid tumoral foci supports the origin of the rhabdoid cells from the classifiable-type RCC. Areas of rhabdoid morphology do not represent muscle metaplastic differentiation. Renal cell carcinoma with rhabdoid morphology may represent a dedifferentiation of a classifiable-type RCC, similar to that of sarcomatoid differentiation. The recognition of RCC-RM is important as it allows for the inclusion of these high-grade malignancies into a category associated with poor prognosis despite lacking the spindle cell component classically identified as sarcomatoid change.     

Dedifferentiated chondrosarcoma of bone with prominent rhabdoid component

Dedifferentiated chondrosarcomas (DDCS) are rare lesions, defined as tumors having a low-grade chondrosarcomatous component with an abrupt transition to a high-grade sarcoma. Although “malignant fibrous histiocytoma” (undifferentiated pleomorphic sarcoma) is the most common high grade saromatous component, many different types of sarcoma have been described. We present a case of dedifferentiated chondrosarcoma with rhabdomyosarcomatous differentiation harboring a prominent rhabdoid tumor component. To our knowledge, rhabdoid morphology in dedifferentiated chondrosarcoma has not been described in the English-language literature. The pathologic and radiologic features of this case are presented.     

横纹肌样型脑膜瘤临床病理学分析

目的探讨横纹肌样型脑膜瘤（rhabdoid meningioma,RM）的临床病理特征。方法对4例RM进行病理形态学观察及免疫组化分析。结果4例发病年龄为11—40岁,平均27岁,3例为单纯型,1例为混合性。瘤细胞呈圆形、多边形,富含胞质呈嗜酸性或嗜中性,均见有胞质或核内假包涵体。瘤细胞呈弥漫性、腺泡状和乳头状排列。免疫组化均表达vimentin和EMA,而HMB45和MG均阴性,仅有1例GFAP呈小灶性阳性。结论RM的诊断应依据细胞学和组织结构的特征,辅以免疫组化分析。     

Smear preparation of intracranial lesions: a retrospective study of 306 cases

A cytohistological correlation with determination of accuracy rate of smear preparation result was done in a retrospective study of 306 cases of intracranial tumors. Cytomorphology of few new entities of CNS tumors are described. The cytological features and WHO grading of the tumors were described on smear preparation. The cases with discrepancy in cytological and histological diagnosis were reviewed again and a final possible diagnosis on smear preparation which should have been given is discussed. The clinical details like the age, sex, and site of the tumors were analyzed. The age range of the patients was from 3 years to 63 years with male:female ratio of 1.5:1. Of the total 306 cases, a cytohistological correlation was seen in 93% cases. Twenty-two (7.3%) cases showed discrepancy between the crush preparation diagnosis and final histopathological diagnosis. Majority of the tumors were located in the cerebral hemisphere (56%) and the most frequently diagnosed tumor was astrocytoma, in particular, pilocytic astrocytoma (18.5%) followed by meningioma (11.9%), medulloblastoma (7.3%), anaplastic oligodendroglioma (5%), ependymoma (4.3%), pituitary adenoma (3.3%), schwannoma (3.3%), etc. A few rarer tumors, in central nervous system like differentiating neuroblastoma, pineocytoma, atypical choroid plexus papilloma, piloxmyxoid astrocytoma, rosette forming glioneuronal tumor, etc. are also described, Smear/crush preparation is a very effective, simple, rapid and reliable technique for the diagnosis and WHO grading of central nervous system tumors. Diagnostic accuracy of cytology with final histopathological report is established with accuracy rate of 93%.     

Loss of INI1 Protein Expression Defines a Subgroup of Aggressive Central Nervous System Primitive Neuroectodermal Tumors

Pediatric embryonal brain tumors can be difficult to classify. Atypical teratoid rhabdoid tumors (ATRT) contain rhabdoid cells, while primitive neuroectodermal tumors (PNETs) are composed of “small round blue cells.” Loss of INI1 is a common event in ATRT; therefore, we investigated if the loss of INI1 protein expression was also observed in central nervous system (CNS) PNET and pineoblastoma. A histological review of 42 CNS PNETs and six pineoblastomas was performed. INI1 expression was assessed by immunohistochemistry. Sequencing was performed on the mutational hotspots of INI1. INI1‐immunonegative tumors were further investigated using fluorescence in situ hybridization. Epithelial membrane antigen (EMA) protein expression was assessed in six CNS PNETs to further define the phenotype. Five CNS PNETs without rhabdoid cell morphology were immuno‐negative for both INI1 and EMA. Of these primary CNS PNET patients, three died <11 months postdiagnosis, which was dissimilar to the INI1‐immunopositive primary CNS PNETs where 18/24 (75%) patients were alive 1 year postdiagnosis. We have identified a small subgroup of CNS PNETs which lack INI1 protein expression, but have no evidence of rhabdoid cell morphology. INI1 protein loss may occur through mechanisms other than gene deletion. INI1 immunohistochemistry should be performed for all CNS PNET cases.     

Mesothelioma with rhabdoid features: an ultrastructural and immunohistochemical study of 10 cases.

Mesotheliomas with rhabdoid morphology are rare and only two individual case reports have been documented in the literature. This author reports a series of 10 cases of mesotheliomas with rhabdoid features, nine of which originated in the pleura and one in the peritoneum. Eight of the patients were men and two were women. Six patients had a history of asbestos exposure. Histologically, seven of the mesotheliomas were epithelioid, two sarcomatoid, and one biphasic. The proportion of the rhabdoid cells seen in these cases constituted 15-75% of the individual tumors. Cytoplasmic staining in the rhabdoid cells was seen for pan-keratin and vimentin in all 10 cases, for keratin 7 in eight of eight, for calretinin in nine of 10, and for keratin 5/6 in seven of nine. Nuclear positivity for WT1 was observed in the rhabdoid cells of four of seven cases and membranous reactivity for mesothelin in four of six, and for podoplanin in two of six. Only one case showed desmin positivity in sparse cells in the nonrhabdoid component of the tumor. All of the cases were negative for CEA, MOC-31, TAG-72, CD15, CD34, bcl2, muscle-specific actin, and TTF-1. Ultrastructural studies revealed paranuclear collections of intermediate filaments, but no evidence of rhabdomyoblastic differentiation was seen. The mean survival of five of the six patients for whom this information was available was 3.8 months. The remaining patient had a survival time of 1 year. It is important for pathologists to be aware that mesotheliomas can present rhabdoid features, not only because they can be confused with other malignancies that can exhibit a similar morphology, but also because of their apparently unusually aggressive behavior. The value of immunohistochemistry and electron microscopy in the differential diagnosis of these tumors is discussed.     

SWI/SNF-deficient thoraco-pulmonary neoplasms

The SWI/SNF complexes are major regulators of gene expression and their alterations occur in a large array of cancers both of epithelial and mesenchymal lineages. Malignant rhabdoid tumors were the first malignancies linked to deregulation of these complexes with the involvement of SMARCB1 in their development but genetic alterations affect all subunits in other malignancies. In the chest and lung regions, SMARCA4 (BRG1) is the most frequently altered subunit and is involved in the pathogenesis of two subtypes of tumors, including bona fide carcinomas (SMARCA4-deficient non-small cell lung cancers) but also undifferentiated tumors that harbor an undifferentiated phenotype close to those of malignant rhabdoid tumors (SMARCA4-undifferentiated tumors). Although their histogenesis is yet to be fully understood, these tumors are associated with distinct clinical and pathological features even though some overlapping features have been reported in rare cases. SMARCA4 deficiency is easily asserted by immunohistochemistry that show the loss of nuclear expression of the protein in the nuclei of tumor cells. These tumors are commonly associated with high-grade cytological features, rhabdoid cytomorphology, solid architecture and extensive necrosis. The typical immunohistochemical signature of SMARCA4-UT combines co-inactivation of SMARCA2 (BRM) and the overexpression of SOX2 and SALL4. No specific therapeutic strategies have been so far developed for SMARCA4-deficient neoplasms. SMARCB1 subunit is involved in the development of several SMARCB1-deficient sarcomas on top of malignant rhabdoid tumors that may develop in the thorax. Malignant rhabdoid tumors affect mostly children of less than 5y. The differential diagnosis includes epithelioid sarcomas, malignant myoepithelial tumors or myoepithelial carcinomas, extra-skeletal myxoid chondrosarcomas and synovial sarcomas.     

Metachronus malignant rhabdoid tumor of the ileum and adenocarcinoma of lung: a unique case report

Malignant extrarenal rhabdoid tumors had been described in a variety of anatomic locations including gastrointestinal tract. Carcinomas of small intestine are quite uncommon neoplasms, and those with rhabdoid differentiation are exceedingly rare. These poorly differentiated tumors pose a great deal of difficulty in diagnosis as well as in deciding whether they are primary or metastatic in origin because malignant rhabdoid tumors or carcinomas with rhabdoid differentiation of other sites can metastasize to the small intestine. They behave more aggressively than the typical adenocarcinomas of the same location. Herein, we report a 52-year-old patient with primary small bowel malignant rhabdoid tumor, who was completely disease-free after the initial presentation and management. Five years later, he was found to have a lung mass proved to be adenocarcinoma, exhibiting focal giant cell differentiation without rhabdoid features.     

Endometrial stromal sarcoma with sex cord-like areas and focal rhabdoid differentiation

An unusual uterine lesion is described in a patient with postmenopausal bleeding. Grossly, a yellow, polypoid mass projected into the uterine cavity. Histological examination showed a distinct biphasic pattern, with areas of typical low-grade endometrial stromal sarcoma and areas where tumour cells were arranged in cords and trabeculae, resulting in a sex cord-like pattern. In these areas the cells assumed a rhabdoid morphology with eccentric vesicular nuclei, prominent nucleoli and eosinophilic hyaline cytoplasmic inclusions. Immunohistochemistry showed positive cytoplasmic staining of both components for vimentin, desmin and the cytokeratin marker CAM 5.2. but no staining for CEA and EMA. Electronmicroscopy revealed prominent paranuclear arrays of intermediate filaments. This is the second reported case of endometrial stromal sarcoma with rhabdoid differentiation and the first documented example of rhabdoid cells in sex cord-like areas. The report adds to the list of diverse neoplasms which may display a characteristic rhabdoid morphology and supports the hypothesis that extrarenal rhabdoid tumours are not a distinct clinicopathological entity. A diagnosis of malignant rhabdoid tumour of the uterus should be considered only when extensive sampling fails to disclose areas with an appearance typical of an endometrial stromal lesion.     

INI1 expression is retained in composite rhabdoid tumors, including rhabdoid meningiomas.

Rhabdoid cells are encountered in specific entities, such as malignant rhabdoid tumor and atypical teratoid/rhabdoid tumor, as well as in composite rhabdoid tumors derived secondarily from other tumor types. Although rhabdoid tumors are uniformly aggressive, distinction of the entity from the phenotype remains important for its therapeutic implications. The majority of malignant rhabdoid tumors and atypical teratoid/rhabdoid tumors affect infants and young children, harbor chromosome 22q deletions, and inactivate the INI1/hSNF5/BAF47 tumor suppressor gene on 22q11.2. In contrast, most composite rhabdoid tumors are diagnosed in adults, with FISH detectable 22q losses the exception rather than the rule. However, this assay remains limited since 22q dosages are maintained in 20-30% of malignant rhabdoid tumors and atypical teratoid/rhabdoid tumors. Furthermore, chromosome 22 losses are common in some parent tumor types, particularly meningiomas. The recently developed INI1 antibody shows loss of nuclear expression in malignant rhabdoid tumors and atypical teratoid/rhabdoid tumors, though its status in composite rhabdoid tumors is largely unknown. Therefore, we utilized immunohistochemistry and FISH to study INI1 expression and 22q dosages, respectively, in 40 composite rhabdoid tumors, including 16 meningiomas, 15 carcinomas, three melanomas, two sarcomas, two glioblastomas, and 1 neuroblastoma. Approximately 70% of rhabdoid meningiomas had a 22q deletion, but this was rare in other tumor types. Except for one retroperitoneal leiomyosarcoma, nuclear INI1 expression was retained in all composite rhabdoid tumors, including meningiomas with 22q deletion. Therefore, we conclude that INI1 immunohistochemistry is a relatively simple, sensitive, and specific technique for distinguishing malignant rhabdoid tumor and atypical teratoid/rhabdoid tumor from composite rhabdoid tumor.     

Adenocarcinomas of the gastrointestinal tract with prominent rhabdoid features

Rhabdoid tumor, first described in kidneys of infants and children, is an aggressive tumor that has been reported in several extrarenal locations. Gastrointestinal tumors with rhabdoid features are extremely rare. The effect of the rhabdoid phenotype on the aggressiveness of gastrointestinal tumors remains unclear. We present four cases of rhabdoid tumors of the gastrointestinal tract involving the esophagus, stomach, and small intestine and discuss the clinicopathologic, immunohistochemical, and ultrastructural features. In the four cases reported herein, the patients' ages ranged from 52 to 73 years, and tumor size ranged from 3.8 to 13 cm in greatest dimension. The noncohesive rhabdoid cells exhibited an eccentric nucleus with a paranuclear inclusion, which was shown by electron microscopic examination to be composed of intermediate filaments. On immunohistochemical staining, the tumor cells were positive for vimentin and cytokeratin. Three patients developed distant metastasis shortly after diagnosis and died of disease within 2 to 10 months after initial presentation. A retrospective review of outcomes of the current cases and previously published literature showed that 12 (75%) of the 16 patients died within 6 months of presentation. Recognition of the rhabdoid phenotype in gastrointestinal tract neoplasms is important because this feature is associated with poor prognosis and unresponsiveness to conventional therapy.     

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).     

Poorly differentiated follicular thyroid carcinoma with rhabdoid phenotype: a clinicopathologic, immunohistochemical and electron microscopic study of two cases.

Poorly differentiated thyroid carcinomas with follicular cell phenotype are not well defined. Different diagnostic criteria have been employed for these tumors, including solid growth, nodular, trabecular, and insular patterns. Cytologic features, such as a predominance of tall and columnar cells, have been considered to be diagnostic of poorly differentiated carcinoma. However, there is no agreement among surgical pathologists regarding morphologic criteria for poorly differentiated thyroid carcinoma. We report two unique thyroid neoplasms that we interpreted as poorly differentiated follicular carcinomas. Nodular, trabecular, and sheetlike patterns predominated in both tumors. They were composed of cells that were focally immunoreactive for thyroglobulin and had large vesicular nuclei with prominent nucleoli. A variable number of cells showed rhabdoid phenotype. The rhabdoid inclusions did not stain for thyroglobulin but contained whorls of intermediate filaments that were vimentin positive. There were foci of necrosis and numerous mitotic figures. Both patients were adults and died with multiple pulmonary metastases. The presence of rhabdoid cells in poorly differentiated follicular carcinomas broadens the spectrum of tumors with rhabdoid phenotype. More cases are needed to determine whether the rhabdoid phenotype is a marker for poorly differentiated follicular carcinoma as well as an independent adverse prognostic factor.     

Rhabdoid epithelioid leiomyosarcoma of the uterine corpus: a case report and literature review

A case of epithelioid leiomyosarcoma of the uterus with rhabdoid phenotype and early rhabdomyoblastic differentiation is described. A 72-year-old woman with a 5-week history of increased abdominal girth was found to have a large pelvic mass. The uterus revealed a large intramyometrial and left adnexal necrotic tumor that had spread to the small bowel mesentery and to the anterior abdominal peritoneum. The tumor was an epithelioid leiomyosarcoma with rhabdoid phenotype and focal early rhabdomyoblastic differentiation, as confirmed by immunohistochemical and ultrastructural techniques. Also called composite extrarenal rhabdoid tumor (CERT), this lesion should be differentiated from malignant mixed müllerian tumor, rhabdomyosarcoma, endometrial stromal sarcoma, and pure rhabdoid tumors of the uterus. The recognition of a rhabdoid phenotype is of clinical importance since these tumors are prone to be aggressive.     

Intracytoplasmic inclusions (including the so-called "rhabdoid" phenotype) in pancreatic endocrine tumors

The cytoplasm of pancreatic endocrine tumors (PET) can show a diverse range of appearances from clear, to oncocytic, to intracellular mucin accumulation, and the presence of intracytoplasmic inclusions. Intracytoplasmic eosinophilic inclusions can vary morphologically and the spectrum ranges from small, dot-like hyaline inclusions, to deeply acidophilic/eosinophilic ones that occupy almost the whole cytoplasm and displace the nucleus eccentrically: the so-called "rhabdoid" phenotype. The aim of this study was to analyze the frequency, morphology, behavior, and relationship to clinicopathological features of large intracytoplasmic inclusions, including the rhabdoid phenotype, in a large number of PET. The morphological features of 84 cases were assessed for the presence of large, globular intracytoplasmic inclusions. Fourteen of 84 cases contained intracytoplasmic inclusions with 5 cases containing cells conforming to the characteristic rhabdoid morphology. The remaining nine cases showed pale intracytoplasmic inclusions. Four of the five cases with rhabdoid cells had spread to lymph nodes and/or peripancreatic fatty tissue. This study confirms that a spectrum of large intracytoplasmic inclusions is encountered in PET, ranging from lightly eosinophilic intracytoplasmic globules to the more typical rhabdoid phenotype (deeply eosinophilic inclusions). This phenotype, in particular the rhabdoid cells, is worthy of attention as a proportion may show lymphovascular invasion with evidence of metastasis at the time of presentation, irrespective of size, mitotic rates, or necrosis.