High‐grade endometrial stromal sarcoma with smooth muscle and skeletal muscle differentiation: Report of a case with cytomorphologic and immunocytologic analysis

We report a case of high‐grade endometrial stromal sarcoma with cytological and immunocytochemical findings. Cytologically, major tumor cells showed round‐to‐short spindle shapes with round‐ to oval‐shaped nuclei and moderately abundant delicate cytoplasm. Tumor cells with tapered shapes and eccentric nuclei were also observed. A few spindle cells having enlarged cigar‐shaped nuclei with conspicuous nucleoli and delicate wispy cytoplasm, which resembled leiomyosarcoma, were intermingled. One rhabdomyoblast cell with both α‐sarcomeric muscle actin and myoglobin was also observed. Most of the tumor cells, including the leiomyosarcomatous spindle cells, were positive for CD10, and negative for desmin and h‐caldesmon. Accordingly, when relatively monotonous round‐to‐short spindle tumor cells and taper‐shaped tumor cells are observed in the female genital tract, high‐grade endometrial stromal sarcoma should be considered in the differential diagnosis. Immunocytochemistry contributed to the correct diagnosis. This case was high‐grade endometrial stromal sarcoma with smooth muscle and skeletal muscle differentiation. Diagn. Cytopathol. 2010. © 2010 Wiley‐Liss, Inc.     

Exfoliative cytology of clear-cell sarcoma metastases in pleural fluid

Two cases of clear-cell sarcoma arising from the leg with widespread metastasis were reported. Exfoliated tumor cells in pleural effusions were round, oval, and slightly pleomorphic. They were seen singly or in clusters of variable size with marked cellular cohesiveness and molding. Their cytoplasm was well-defined, clear, or finely granular, and contained S-100 protein and periodic acid-Schiff positive material that was digestible by diastase. Tumor-cell nuclei were round and hyperchromatic with irregular chromatin clumping, and showed conspicuous nucleoli.     

Role of Electron Microscopy in Metastatic Endometrial Stromal Tumors

Endometrial stromal tumors may pose a problem in diagnosis when they appear as metastatic lesions without a known primary tumor. To determine the usefulness of electron microscopy in identifying them in these situations, optimally fixed low-grade stromal sarcomas (five), normal endometrial specimens (six), and malignant mesodermal mixed tumors (four) were studied. The endometrial stromal sarcomas had a general resemblance to normal proliferative endometrial stroma, being composed of undifferentiated cells, fibroblasts, and myofibroblasts. One stromal tumor showed evidence of partial epithelial differentiation. One of the four malignant mesodermal mixed tumors had a fibrosarcomalike component, but there was insufficient resemblance to normal endometrial stroma to indicate a relationship between the two. Together with a review of the literature, this study indicates that electron microscopy is useful in the diagnosis of low-grade endometrial stromal tumors by demonstrating characteristic cellular findings as well as a lack of features specific for other round cell and spindle cell neoplasms.     

Mixed endometrial stromal and smooth muscle tumor: Report of a case with focal anaplasia and early postoperative lung metastasis

A rare case of a mixed endometrial stromal and smooth muscle tumor arising in the uterus of a 74‐year‐old woman is reported. The patient underwent hysterectomy for an enlarging uterine mass, and a large intramural tumor, showing marked central hyaline necrosis with calcification, was found. The tumor consisted of an admixture of a low‐grade endometrial stromal sarcoma (ESS) and a fascicular proliferation of spindle cells suggesting smooth muscle differentiation, and a characteristic ‘star‐burst’ appearance was found. In the ESS region, there were a few small foci of anaplasia where large polygonal cells with atypical nuclei and abundant eosinophilic cytoplasm proliferated, and the proliferative activity was locally increased in these foci. A small metastatic nodule appeared in the lung nine months after the hysterectomy, and the resected metastatic lesion showed features of anaplastic spindle cell sarcoma which was immunoreactive for CD10 but not for smooth muscle markers. Mixed endometrial stromal and smooth muscle tumors should be regarded as malignant neoplasms with the potential for hematogenous metastasis, particularly when they contain foci of cellular anaplasia.     

Cytopathology of malignant mesothelioma of the pleura in fine-needle aspiration biopsy

The cytologic findings in fine-needle aspiration biopsy (FNAB) of 9 histologically, immunohistochemically, and ultrastructurally confirmed malignant mesotheliomas of the pleura were reviewed. There were 4 epithelial malignant mesotheliomas (EMM), 3 sarcomatous mesotheliomas (SM), 1 mixed malignant mesothelioma (MMM), and 1 poorly differentiated malignant mesothelioma (PDMM). In FNAB, three EMMs yielded polygonal malignant cells with oval nuclei and prominent nucleoli, singly, in small sheets, and in tridimensional clusters with smooth or lobulated contours. In one EMM, only atypical mesothelial cells with prominent nucleoli were seen singly and in loose aggregates. In FNAB, two SM showed malignant spindle-shaped cells (MSC) with scant, ill-defined cytoplasm singly and in loose clusters. Cohesive clusters of elongated and polygonal cells with ill-defined, clear cytoplasm and pleomorphic nuclei containing small or prominent nucleoli were observed in one SM, with extensive clear-cell changes. In needle aspirates, the MMM showed polygonal malignant cells in clusters admixed with MSC. The PDMM displayed single and clustered large pleomorphic malignant cells, with prominent single or multiple nucleoli. Electron microscopic examination of minute tissue fragments retrieved from the FNAB in 2 cases of EMM revealed epithelial mesothelial cells with well-formed desmosomes and long slender microvilli (LSM) on the free tumor cell surfaces. In one case, LSM in direct contact with collagen fiber bundles in the tumor tissue matrix were observed, supporting the diagnosis of an invasive EMM. Diagn. Cytopathol. 1999;21:253-259.     

The cells of benign and malignant hemangiopericytomas in aspiration biopsy

Samples obtained by fine-needle biopsy of two benign and one malignant hemangiopericytoma revealed tumor cells with round, oval, or spindle-shaped nuclei, with variable and ill-defined filmy cytoplasm. The nuclei had a finely granular chromatin pattern with or without inconspicuous nucleoli. They were seen singly or in loose or dense cellular clusters. Focal gland-like arrangement of tumor cells was noted in some cellular clusters. Benign endothelial cells were seen among tumor cells and were not cohesive to the latter. The benign and malignant nature of hemangiopericytoma cannot be predicted by examination of the cells present in the aspirates. Also, a specific diagnosis of hemangiopericytoma could not be made on cytologic basis alone as cells of hemangiopericytoma were difficult to differentiate from those of other spindle-cell mesenchymal tumors.     

Hyaline matrix material in high-grade endometrial stromal sarcoma diagnosed by fine-needle aspiration: Case report

We present a case of a high-grade endometrial stromal sarcoma metastatic to the abdomen with an unusual extracellular hyaline matrix material seen on fine needle aspiration biopsy. The patient was initially diagnosed with a stage IIIA high-grade endometrial stromal sarcoma and had received four cycles of chemotherapy over the past year. She subsequently developed an abdominal mass that consisted of discohesive small cells with scanty cytoplasm on fine needle aspiration. On the Diff-Quik-stained smears, metachromatic, extracellular hyaline material was identified. This appeared on the Papanicolaou-stained smear as cyanophilic material and did not react with reticulin stain. This case emphasizes the importance to the cytopathologist of including endometrial stromal sarcoma in the differential diagnosis of hyaline matrix material. Diagn. Cytopathol. 16:151–155, 1997. © 1997 Wiley-Liss, Inc.     

低度恶性子宫内膜间质肉瘤临床病理分析

目的 探讨低度恶性子宫内膜问质肉瘤(LESS)的临床病理学特征、诊断和鉴别诊断。方法 分析17例LESS的临床病理特点,通过网织纤维染色、免疫组化染色和电镜观察来研究其病理学特征。结果 LESS临床上主要表现为阴道不规则流血。HE染色见肿瘤组织成巢团样浸润,肿瘤细胞圆形、卵圆形或梭形。肿瘤内有大量的小血管。网织纤维染色见网状纤维丰富,围绕瘤细胞生长。肿瘤细胞14例CD10阳性,12例ER阳性,13例PR阳性,3例actin阳性,C1934、CDll7、Melan—A肿瘤细胞均阴性。电镜观察见肿瘤细胞胞质内的中间丝呈杂乱无序的排列。结论 LESS易误诊,确诊主要依靠组织病理学和免疫组织化学;病理形态上看似良好的低度恶性子宫内膜间质肉瘤,预后不一定好。     

High grade endometrial stromal sarcoma on thinprep

High grade endometrial stromal sarcoma (HGESS) is an uncommon malignancy recently re‐defined in the new WHO classification of endometrial stromal tumors. In this article, we discuss the differential diagnoses of metastatic HGESS in a fine needle aspiration (FNA) of a lymph node and compare the cytomorphology of HGESS in ThinPrep [(TP), Hologic Inc., Boxborough, MA] to conventional smears (CS). The patient had a history of stage I HGESS, status‐post supracervical hysterectomy without regional lymph node metastases. Her post‐operative course was complicated by pelvic fluid collections and enlarging para‐aortic lymph nodes. Diff‐Quik (DQ)‐stained and Papanicolaou (Pap)‐stained smears from a para‐aortic lymph node FNA demonstrated a cellular specimen with monomorphic population of plump to oval cells with scant, wispy cytoplasm in aggregates and as single cells. The nuclei showed fine chromatin and small inconspicuous nucleoli. Compared to the CS, HGESS cells in the TP showed similar cytological features, with the exception that the nuclei were slightly smaller, hyperchromatic, and the chromatin pattern was attenuated. In the absence of prior clinical history, the cytomorphology of metastatic HGESS in a lymph node can be difficult to differentiate from a lymphoma, a variety of metastatic spindle cell tumors or metastatic carcinoma. Immunohistochemical analysis and comparison with the primary tumor can be useful in proving the nature of the malignant cells. The cytomorphology of HGESS on TP correlated well in both single cells and aggregates when compared to CS. The differences noted were decreased nuclear size, nuclear hyperchromasia, and slightly attenuated nuclear detail on TP. Diagn. Cytopathol. 2015;43:756–762. © 2015 Wiley Periodicals, Inc.     

Adult granulosa cell tumor of the ovary: fine-needle-aspiration cytology of 10 cases and review of literature

Adult granulosa cell tumor (GCT) of the ovary is mostly diagnosed in postmenopausal women. They typically secrete estrogen, which stimulates the endometrium to proliferate and cause abnormal bleeding. This study reviews the cytologic features of adult GCT of the ovary diagnosed by fine-needle aspiration (FNA). We reviewed slides from ten cases diagnosed by CT guided FNA from 1995 to 2007 at our institutions. Smears were stained with Diff-Quik and Papanicolaou stains. Patient's history and histologic diagnosis were also available and reviewed for all cases. The patients ranged in age from 39 to 83 yr. All 10 cases were hypercellular with both large and small overlapping cell clusters and individual cells. The cytologic features identified included: naked nuclei (10/10 cases), Call-Exner bodies (7/10 cases), blood vessels with prominent perivascular tumor cell growth (4/10 cases), spindle-shaped hyperchromatic stromal cells within cellular clusters (6/10 cases), mixed inflammation (3/10 cases), tumor cell necrosis (1/10 cases), and prominent metachromatic stroma seen in association with blood vessels (1/10 cases). Moderate to scant delicate cytoplasm was also seen (10/10 cases). Small, punctuate cytoplasmic vacuoles were also noted (7/10 cases) and were occasionally prominent (3/10 cases). In general nuclear to cytoplasmic ratios were high although lower than those typically seen in a lymphoma or small-cell carcinoma. Nuclei were generally centrally located although eccentrically located nuclei were consistently seen in a minority of cells. Nuclei were monotonous in size showing slightly convoluted (occasional rentiform and fetiform nuclei) to polygonal outlines. Prominent, central nucleoli were also seen (4/10 cases). Nuclear grooves were also seen (9/10 cases). No atypical mitotic activity was identified in any of the 10 cases (0/10 cases). In summary, the above cytologic features can also help in the cytologic diagnosis of adult GCTs.     

Myxoid endometrial stromal sarcoma of the uterus

A rare case of a myxoid type of endometrial stromal sarcoma of the uterus in a 41-year-old woman is reported. A tumor was found in the myometrium and was well circumscribed, measuring 9 x 7 x 7 cm in size. The tumor was mainly composed of a hypocellular area with tumor cells separated by prominent myxoid stroma. The tumor cells were spindle-shaped and resembled endometrial stromal cells. Numerous small thin-walled vessels were seen throughout the tumor. Immunohistochemically, the tumor cells were diffusely stained for estrogen and progesterone receptors and CD10, and focally and weakly for HHF35, alpha-smooth muscle actin and desmin, but not stained for h-caldesmon. These results indicated that the tumor originated from endometrial stromal cells. The tumor had an increased mitotic activity (MIB-1 labeling index: 1-10%), and focally showed nuclear pleomorphism. Thus, this tumor had a malignant potential and was diagnosed as a myxoid type of low-grade endometrial stromal sarcoma. The patient is currently well with no evidence of local recurrence or metastasis 21 months after the operation. This case indicates a wide morphological spectrum of endometrial stromal tumor. A myxoid endometrial stromal sarcoma should be considered in the different diagnosis of the intramural myxoid tumors in the uterus.     

Large cell neuroendocrine carcinoma of the maxillary sinus on fine needle aspiration cytology: Report of a rare case with a focus on pitfalls in diagnosis

Head and neck large cell neuroendocrine carcinoma (LCNEC) is a rare high‐grade malignant tumor with neuroendocrine differentiation. We report a case of LCNEC causing difficulty in cytological diagnosis. A 60‐year‐old man with right‐sided face pain presented with a swelling at the right cheek, and he complained of right nasal obstruction and lacrimation. Preoperative fine‐needle aspiration cytology (FNAC) showed high cellularity, with a moderate number of clusters of tumor cells on an abundant necrotic background. The clusters were arranged in sheet structures with palisading, and were cohesive with overlapping. The tumor cells had comparatively abundant cytoplasm, with conspicuous large, irregular nucleoli with a fine granular chromatin pattern. Mitotic figures were observed easily. On immunocytochemistry using LBC smear, tumor cells were negative for p40. High‐grade carcinoma other than non‐keratinizing squamous cell carcinoma was suggested from these findings on FNAC. The pretreatment histological biopsy sample revealed tumor cells with solid growth pattern, necrotic materials and large polygonal cells with abundant cytoplasm, fine granular chromatin, and conspicuous nucleoli. Head and neck LCNEC with abundant cytoplasm, fine granular chromatin patterns, prominent nucleoli, and necrotic background were very characteristic of LCNEC. If considered carefully, these findings can enable us to exclude the majority of non‐keratinizing squamous cell carcinomas, and FNAC using ancillary technique can be very useful for proper diagnosis.     

Syncytial variant of nodular sclerosing Hodgkin's disease: Fine-needle aspiration findings in two cases

The syncytial variant is a recently described, uncommon form of nodular sclerosing Hodgkin's disease that was previously termed “sarcomatoid.” In addition to foci of typical sclerosis, it is characterized histologically by sheets or clusters of mononuclear Reed-Sternberg variants. These may be arranged around areas of necrosis with variable numbers of neutrophils. In excised material, differential diagnostic considerations include non-Hodgkin's malignant lymphoma, granulocytic sarcoma, malignant melanoma, metastatic carcinoma, thymoma, and metastatic germ cell tumor. We describe the fine-needle aspiration cytologic finding in two examples of this entity. Cohesive clusters and sheets of malignant cells with clear cytoplasm, vesicular nuclei, and prominent nucleoli are easily mistaken for metastatic carcinoma or germ cell tumor. Ancillary tests useful in this differential diagnosis are discussed. Diagn. Cytopathol. 1997;17:477–479. © 1997 Wiley-Liss, Inc.     

Cytodiagnosis of benign and malignant Hürthle cell lesions of the thyroid by fine-needle aspiration biopsy.

Eighty-two Hürthle cell (HC) lesions of the thyroid with cytologic evaluation by fine-needle aspiration biopsy (FNAB) were reviewed. In 17 cases the FNAB was not diagnostic because the fine-needle aspirates (FNAs) were too scanty in cellularity. Among the remaining 65 lesions, there were 45 HC adenomas (HCAs), six non-neoplastic HC nodules (NHCNs), 10 primary HC carcinomas (HCCs), and four metastatic HCCs. Forty-four HCAs were diagnosed as HC tumor (HCT), and one HCA was wrongly diagnosed as medullary carcinoma. All six NHCNs were wrongly diagnosed as HCT. Of 10 primary HCCs, there were diagnosed as HCT and seven as suspected HCC. Four metastatic HCCs were correctly diagnosed. The FNAs from 38 HCAs and four NHCNs were predominantly composed of large monomorphic HCs with oval nuclei, inconspicuous nucleoli, and abundant, well-defined, granular cytoplasm present singly, in acinar arrangement, and in monolayered sheets of variable sizes. Nuclear pleomorphism and prominent nucleoli were noted in seven HCAs and two NHCNs. Occasional small syncytial tumor cell clusters (STCCs) were noted in six cases, and a few naked tumor cell nuclei (NTCN) were observed in 16 cases. The FNAs from 14 HCCs were hypercellular. In all cases tumor cells were relatively small and showed monomorphic or pleomorphic nuclei, prominent nucleoli, and ill-defined cytoplasm. STCCs of variable sizes were present in abundance in 10 cases, and numerous NTCN were noted in 12 cases. In two HCCs, the tumor cells with well-defined cytoplasm were present singly and in cohesive sheets, and no STCCs or NTCN were observed. Thus, the presence of small tumor cells with ill-defined cytoplasm and prominent nucleoli in syncytial clusters and abundant NTCN in the FNA of a thyroid nodule should alert the observer about the strong possibility of an HCC.     

Extrauterine mesodermal (müllerian) adenosarcoma: a clinicopathologic analysis of five cases.

Five extrauterine examples (three pelvic and two ovarian) of a distinctive mesodermal (müllerian) mixed tumor previously described to occur in the uterus and designated müllerian adenosarcoma are reported. The tumors were diagnosed during the fifth to eight decades of life. They usually formed very large, partly cystic masses, which had occasionally spread to adjacent organs by the time of operation. On microscopic examination the tumors consisted of benign-appearing neoplastic glands lying in a sarcomatous stroma. The glands were lined by a variety of müllerian epithelial cell types, and the stromal element resembled endometrial stromal sarcoma. Three patients had malignant courses manifested by intrabdominal recurrence, distant metastases, or both. This tumor should be clearly distinguished from the more common forms of mesodermal (müllerian) mixed tumor in which the epithilial as well as the stromal component is malignant and the prognosis is much more grave.     

Breakages at YWHAE,FAM22A,and FAM22B loci in uterine angiosarcoma: A case report with immunohistochemical and genetic analysis

Described herein is the first reported case of a uterine angiosarcoma with breakages at three loci, YWHAE (17p13), FAM22A (10q23) and FAM22B (10q22). A 62-year-old postmenopausal woman was found to have endometrial thickening of her uterus. An endometrial biopsy indicated a malignant, spindle cell neoplasm. A total hysterectomy with bilateral salpingooophorectomy was performed. Histologic examination of the uterine specimen showed a malignant tumor consisting of irregular rudimentary vascular channels and solid small nests diffusely infiltrating to the middle of the myometrial wall. The tumor cells were epithelioid, and displayed eosinophilic cytoplasm and vesicular nuclei in some areas of the tumor. Immunohistochemically, the tumor cells showed vascular differentiation; they were diffusely positive for CD31 and D2-40 but were negative for factor VIII and CD34. In the course of the procedure of differential diagnoses, we included fluorescence in situ hybridization analysis for detection of a FAM22B-YWHAE fusion gene resulting from t(10;17)(q22;p13), recently reported in a series of endometrial stromal sarcoma, and unexpectedly identified breakages at three loci, i.e. YWHAE (17p13), FAM22A (10q23) and FAM22B (10q22). Collectively, these findings suggest that abnormality in the loci of YWHAE, FAM22A and FAM22B, which are known to be associated with oncogenesis of endometrial stromal sarcoma, may contribute to the development of uterine angiosarcoma.     

Glassy cell carcinoma of the endometrium: a case report and review of the literature

Glassy cell carcinomas are composed of malignant cells showing a "ground glass" cytoplasm, distinct cell membranes, and large nuclei with prominent nucleoli. To our knowledge, only 12 cases of glassy cell endometrial carcinomas (EGCC) have been reported until now. A 63-year-old patient complaining of irregular vaginal bleeding underwent hysteroscopy-guided biopsy revealing a well-differentiated endometrial endometrioid adenocarcinoma. The patient underwent left salpingo-oophorectomy, total abdominal hysterectomy, and pelvic lymphadenectomy. The final diagnosis was FIGO stage IB poorly differentiated endometrial adenosquamous carcinoma with > 90% of glassy tumor cells. The patient is alive, with no evidence of disease for 69 months after diagnosis. We describe an additional case of EGCC and review the data of the literature, emphasizing the need to strictly define the criteria for the diagnosis and the potential usefulness of assessing biologic parameters for the prognostic characterization of this rare entity.     

Cytopathology of insular carcinoma of the thyroid.

Four pure insular carcinomas (IC) and one IC with focal anaplastic carcinoma (AC) of the thyroid with cytologic evaluation by fine-needle aspiration (FNA) were reviewed. The needle aspirates from the four pure ICs revealed abundant monomorphic follicular cells present singly, in small, loose aggregates, and in cohesive trabecular and acinar clusters. Tumor cells showed fragile, ill-defined, granular cytoplasm and oval nuclei with conspicuous or inconspicuous nucleoli. The case of IC with focal AC yielded, in addition to the follicular cells as seen in the FNA of the 4 cases of pure IC, large pleomorphic malignant cells with prominent nucleoli that were characteristic for an AC, giant-cell type. No intact insulae of tumor cells were identified in any of the 5 cases. Thus, a thyroid IC may be suspected if abundant cohesive and dyshesive monomorphic follicular cells are present in the tumor FNA. However, a firm diagnosis of thyroid IC can only be made by histologic examination of the excised tumor.     

Primary signet-ring stromal tumor of the testis

We present, in a 47-year-old man, the first case of the signet-ring stromal tumor of the testis. The tumor was located beneath the tunica albuginea surrounded by the testicular tubules and rete testis. It was sharply circumscribed by a thin and irregular fibrous capsule. Histologically, it was composed of cells with a widespread signet-ring cell change separated by fibrous stroma. In some places, the signet-ring cells formed vague Indian files, thus resembling metastatic carcinomas with signet-ring cell morphology. Under high magnification, most of the cytoplasm of the tumor cells was seen to be replaced by an empty clear vacuole which pushed the nuclei to the periphery of the cells. Some of the nuclei were indented by the cytoplasmic vacuoles, others were without indentation. Only in a small area did the tumor show cells without a signet-ring cell change. They looked like epithelioid fibroblasts forming abortive and vaguely tubular structures. Mitoses and necroses were absent. Mucicarmine and PAS stains were negative. Immunohistochemically, the tumor was vimentin positive and it was negative with antibodies to cytokeratins, inhibin, prostatic acid phosphatase, prostate-specific antigen, smooth muscle actin, S-100 protein, EMA and calretinin. The signet-ring stromal tumor of the testis is thus similar morphologically and immunohistochemically to the signet-ring stromal tumor of the ovary. The patient was free of recurrence and metastasis 3 years after the excision.     

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.