Epithelioid Tumor Research Articles

Microsatellite Genotyping to Distinguish Somatic β-HCG Secreting Carcinoma from Epithelioid Trophoblastic Tumor.

Objective. Morphologically, β-HCG secreting somatic carcinoma can be difficult to distinguish from epithelioid trophoblastic tumors (ETT). However, their distinction is critical due to their potentially differing prognoses and choice of chemotherapy. Presence of biparental alleles in ETT can be identified with molecular testing. We describe a patient who presented with metastatic carcinoma and elevated serum β-HCG and contrast this to an ETT in another patient. Data and Results. A 32-year-old female with recent possible miscarriage presented with pulmonary emboli and was found to have an increased serum β-HCG, a retroduodenal mass, and multiple nodules in her lungs, liver, and para-aortic lymph nodes. Biopsy showed a β-HCG and p63 positive epithelioid neoplasm with otherwise noncontributory immunohistochemistry. Molecular testing for biparental alleles in repeated length polymorphisms was negative, consistent with somatic origin. The second patient was a 35-year-old pregnant female with increased serum β-HCG and a uterine epithelioid tumor positive for β-HCG. Clinical and pathologic findings were characteristic of ETT and molecular testing was not required. These 2 cases illustrate that β-HCG secreting tumors of different etiologies may have similar appearances, and when clinical and/or IHC findings are inconclusive, molecular testing may be useful.

Thoracic epithelioid malignant vascular tumors: a clinicopathologic study of 52 cases with emphasis on pathologic grading and molecular studies of WWTR1-CAMTA1 fusions.

Malignant thoracic epithelioid vascular tumors are an uncommon and heterogenous group of tumors that include low-grade to intermediate-grade epithelioid hemangioendothelioma (EHE) and high-grade epithelioid angiosarcoma (EAS). We examine the morphologic and immunohistochemical features of 52 malignant epithelioid vascular tumors (10 low-grade EHE, 29 intermediate-grade EHE, and 13 EAS) involving the thorax (lung, pleura, mediastinum, heart, great vessels) including cases with exclusively thoracic disease (35) and with multiorgan disease including the thorax (17). Intermediate-grade EHE differs from low-grade EHE by the presence of necrosis, increased mitotic activity, and increased atypia. Morphologic features such as intranuclear inclusions, intracytoplasmic vacuoles, and stromal changes (chondroid, myxoid, or hyalinized stroma) are seen more frequently in EHE, whereas blood lakes, proliferation of slit-like vessels, and prominent nucleoli favor EAS. Fluorescence in situ hybridization analysis showed CAMTA1-WWTR1 fusions in 4/7 low-grade and 23/23 intermediate-grade EHE (P<0.001). In EAS, CAMTA1 rearrangement was negative in all cases, whereas a WWTR1 complex abnormality was found in 1/5 cases (P<0.001). This offers an objective means of differentiating intermediate-grade EHE from EAS, especially on limited biopsies. All cases show expression of at least 1 vascular marker, which allows differentiation from primary thoracic epithelial malignancies, although keratin expression is a potential pitfall with 29% of EHE and 25% of EAS showing keratin expression. Survival analysis shows that higher tumor grade for all tumors (P=0.026) as well as lung and pleural tumors only (P=0.010) and the presence of pleural involvement in lung and/or pleural tumors (P=0.042) correlate with poor prognosis.

A misdiagnosed melanoma: a case of cutaneous epithelioid malignant peripheral nerve sheath tumor

Malignant Peripheral Nerve Sheath Tumor (MPNST) is a rare soft tissue sarcoma that can occur in superficial locations. Histologically it is categorized into two variants: a conventional/spindled and an epithelioid variant. The latter one is very rare and can be confused histologically with malignant melanoma as it is diffusely positive for S100-protein. Herein we present a case that was initially misdiagnosed as malignant melanoma and discuss morphological and immunohistochemical clues to reach a correct diagnosis.

Follicular dendritic cell sarcoma: report of two cases and literature review

Follicular dendritic cell sarcoma is a rare neoplasm, first described in 1986 by Monda. Case 1: A female patient, 50-year-old performed abdominal computed tomography scan that detected a tumor lesion of 8.0 cm in the mesentery. She underwent resection of the lesion. Microscopic examination revealed epithelioid neoplasm, interspersed with lymphocytes, and positive immunohistochemical staining for CD21 and CD35. The patient underwent adjuvant chemotherapy. Case 2: A male patient, 21-year-old presented right-sided neck mass measuring 7.0 cm. The biopsy revealed proliferation of spindle cells, interspersed with inflammatory infiltrate and storiform arrangement, and positive immunohistochemical staining for CD21 and CD23. The patient underwent neoadjuvant radiotherapy and surgical resection.

A rare case report: atypical epithelioid leiomyosarcoma of urinary bladder

Background Benign and malignant mesenchymal tumours of the urinary bladder are rare. Non-epithelial tumours account for 1–2% of all primary urinary bladder neoplasms. Among them, leiomyosarcoma is the most common type, representing only 0.1% of bladder cancers. It has three distinct histological variants: the classical spindle cell subtype, the myxoid subtype and the rare epithelioid subtype.1 Case report A 54-year-old female became increasingly symptomatic with urge incontinence and gross haematuria associated with significant weight loss. Abdominal ultrasound showed a large mass in urinary bladder. Core biopsy and then radical cystectomy show sheets of atypical cells which are mostly epithelioid or polygonal in shape. The main differentials include epithelioid leiomyosarcoma, sarcomatoid carcinoma and other sarcomas. Immunostains for smooth muscle markers, calponin, h-caldesmon, SMA, cytokeratin stains, S100 stains, HMB45, c-kit and myoglobin stain were performed. Other immunomarkers of epithelioid tumours were also checked. Overall features are consistent with an epithelioid leiomyosarcoma with urinary bladder involvement. Discussion Epithelioid leiomyosarcoma is a very rare tumour of the urinary bladder. The use of immunohistochemical staining is of value in assisting diagnosis.

Desmoplastic Small Round Cell Tumor, a "Floating Island" Pattern in Pleural Fluid Cytology: A Case Report and Review of the Literature.

Desmoplastic small round cell tumor (DSRCT) is a rare aggressive sarcoma with characteristic clinical and pathologic features. It typically involves pelvic and abdominal organs of young male patients, and patients usually present at advanced stage with poor prognosis. A few reports are available describing the cytopathologic features of DSRCT in serous effusions, with the majority of published cases depicting undifferentiated small blue cells that need to be distinguished from other small blue cell tumors. We report an interesting case of DSRCT involving a pleural effusion with a “floating island” pattern that has been described in hepatocellular carcinoma, renal cell carcinoma, and adrenal cortical carcinoma. In our case, the epithelioid tumor cells form cohesive aggregates surrounded by a single layer of spindle cells, mimicking the “endothelial wrapping” in other tumors with “floating island” patterns. We demonstrate, by ancillary testing, that these peripheral spindle cells are tapered/flattened DSRCT cells, in contrast to endothelial wrapping cells, as seen in other tumors with this unique cytomorphology. To our knowledge, this is the first case report describing DSRCT showing a “floating island” pattern that needs to be differentiated from metastatic hepatocellular carcinoma, renal cell carcinoma, and adrenal cortical carcinoma in effusion cytology.

A case report: malignant epithelioid angiomyolipoma

A 55-year-old lady presented with a history of left sided abdominal pain, fever and recent 10 kg weight loss. Radiological study showed a left renal mass. Macroscopic examination revealed a 1284 g kidney with a large solitary lower pole tumour, measuring 170 mm in maximum dimension. The tumour demonstrated a variegated solid yellow cut-surface with extensive haemorrhage and necrosis. Light microscopy showed an oncocytic epithelioid tumour. The cells were large with abundant eosinophilic cytoplasm and pleomorphic nuclei with prominent nucleoli. In addition, there were scattered rhabdoid-like and ganglion-like cells with numerous admixed florette-type multinucleated giant cells. Mitotic figures were sparse. There were no areas of conventional angiomyolipoma. Immunohistochemically, the tumour was positive for Melan-A, HMB-45, E-cadherin, S100 and vimentin. They were negative for CK7, CK AE1/AE3, CD117, CD10, SMA and desmin. The morphological and immunohistochemical features were that of a malignant epithelioid angiomyolipoma. Epithelioid angiomyolipoma is a rare mesenchymal neoplasm with a malignant potential. It belongs to the PEComa family and mimics a variety of oncocytic or clear cell neoplasms. It often poses diagnostic difficulties and is thus an important entity to recognise in order to optimise patient management.

Myxoid Epithelial Leiomyoma of the Vulva: A Case Report and Literature Review.

Leiomyoma of vulva is rare, and usually misdiagnosed clinically as Bartholin cyst. It usually presents spindle-shaped tumor cells, but some rare cases consisted mainly of atypical epithelioid tumor cells. We report here a case of 30-year-old woman consulting with a vulvar mass of 7 cm in the Bartholin glands area. The lesion was surgically excised with its capsule completely. Pathological examination and immunochemistry showed characteristic of epithelioid leiomyoma with myxoid stroma with both estrogen receptor (ER) and progesterone receptor (PR) staining negative, which was really rare as only 2 cases of vulvar leiomyoma with both ER and PR were reported before.

Focal nodular hyperplasia coexistent with hepatoblastoma in a 36-d-old infant

Focal nodular hyperplasia (FNH) is a benign hepatic tumor characterized by hepatocyte hyperplasia and a central stellate scar. The association of FNH with other hepatic lesions, such as adenomas, hemangiomas and hepatocellular carcinoma, has been previously reported, but FNH associated with another hepatic tumor is rare in infants. Here we report a case of FNH coexistent with hepatoblastoma in a 36-d-old girl. Computed tomography (CT) imaging showed an ill-delineated, inhomogeneous enhanced mass with a central star-like scar in the right lobe of the liver. The tumor showed early mild enhancement at the arterial phase (from 40HU without contrast to 52HU at the arterial phase), intense enhancement at the portal phase (87.7HU) and 98.1HU in the 3-min delay scan. A central scar in the tumor presented as low density on non-contrast CT and slightly enhanced at delayed contrast-enhanced scanning. This infant underwent surgical resection of the tumor. Histopathology demonstrated typical FNH coexistent with a focal hepatoblastoma, which showed epithelioid tumor cells separated by proliferated fibrous tissue.

BRAFV600E immunopositive melanomas show low frequency of heterogeneity and association with epithelioid tumor cells: a STROBE-compliant article.

Treatment of BRAFV600E-mutant melanoma by small molecule inhibitors that target BRAFV600E or MEK kinases is increasingly used in clinical practice and significantly improve patient outcome. However, patients eventually become resistant and therapeutic improvement is required. Molecular diversity within individual tumors (intratumor heterogeneity) and between tumors within a single patient (intrapatient heterogeneity) poses a significant challenge to precision medicine. Using immunohistochemistry, we determined the extent of BRAFV600E intratumor and intrapatient heterogeneity and the influence of morphological heterogeneity in a large series of 171 melanomas of 81 patients. The BRAFV600E mutation rate found in our melanoma series is 44%, with none of 22 (0%) melanoma in situ, 23 of 56 (41%) primary tumors, 28 of 59 (48%) regional metastases, and 24 of 34 (71%) distant metastases harboring the mutation. In general, a diffuse homogeneous immunostaining was seen, even in tumors consisting of more than one cell type, that is, epithelioid, spindle, and/or small cell types. Nevertheless, BRAFV600E-mutant melanomas more often had a purely epithelioid cell population (P=0.063), that is more evident among distant metastases (P=0.014). Only two of 75 (3%) mutated specimens (one primary and one metastasis) displayed heterogeneous BRAFV600E expression. The primary tumor was also morphologically heterogeneous and exclusively displayed BRAFV600E in the epithelioid component, confirming an association between BRAFV600E and epithelioid cells. Twenty-eight of 30 patients (93%) had concordant BRAFV600E mutation status between their tumors. Taken together, BRAFV600E intratumor and intrapatient heterogeneity in melanoma is diminutive, nevertheless, the identified exceptions will have important implications for the clinical management of this disease.

A Rare Case of Mesothelioma Showing Micropapillary and Small Cell Differentiation with Aggressive Behavior

Pleural mesothelioma is a rare neoplasm and roughly 70% are the epithelioid type, which is characterized by proliferation of epithelioid tumor cells with a tubulopapillary growth pattern [1]. There have been few reports of mesothelioma having a micropapillary pattern [2] and a small cell component [3]. To the best of our knowledge, there has been no previously reported case containing both micropapillary and small cell components. Herein, we report a rare case of mesothelioma with micropapillary component and small cell differentiation exhibiting aggressive behavior in a 59-year-old woman.

Programmed death ligand 1 expression and tumor-infiltrating lymphocytes in glioblastoma

Immune checkpoint inhibitors targeting programmed cell death 1 (PD1) or its ligand (PD-L1) showed activity in several cancer types. We performed immunohistochemistry for CD3, CD8, CD20, HLA-DR, phosphatase and tensin homolog (PTEN), PD-1, and PD-L1 and pyrosequencing for assessment of the O6-methylguanine-methyltransferase (MGMT) promoter methylation status in 135 glioblastoma specimens (117 initial resection, 18 first local recurrence). PD-L1 gene expression was analyzed in 446 cases from The Cancer Genome Atlas. Diffuse/fibrillary PD-L1 expression of variable extent, with or without interspersed epithelioid tumor cells with membranous PD-L1 expression, was observed in 103 of 117 (88.0%) newly diagnosed and 13 of 18 (72.2%) recurrent glioblastoma specimens. Sparse-to-moderate density of tumor-infiltrating lymphocytes (TILs) was found in 85 of 117 (72.6%) specimens (CD3+ 78/117, 66.7%; CD8+ 52/117, 44.4%; CD20+ 27/117, 23.1%; PD1+ 34/117, 29.1%). PD1+ TIL density correlated positively with CD3+ (P < .001), CD8+ (P < .001), CD20+ TIL density (P < .001), and PTEN expression (P = .035). Enrichment of specimens with low PD-L1 gene expression levels was observed in the proneural and G-CIMP glioblastoma subtypes and in specimens with high PD-L1 gene expression in the mesenchymal subtype (P = 5.966e-10). No significant differences in PD-L1 expression or TIL density between initial and recurrent glioblastoma specimens or correlation of PD-L1 expression or TIL density with patient age or outcome were evident. TILs and PD-L1 expression are detectable in the majority of glioblastoma samples but are not related to outcome. Because the target is present, a clinical study with specific immune checkpoint inhibitors seems to be warranted in glioblastoma.

Proximal-type epithelioid sarcoma of pharynx: A case report with immunohistochemical study

Epithelioid sarcoma (ES) usually occurs in extremities. ES shows characteristic granulomatous morphologies, and its prognosis is not so poor. Proximal-type ES (PT-ES) is a variant of ES, and is characterized by central locations, severe atypical features, and poor prognosis. Both ES and PT-ES histologically show epithelial and sarcomatous patterns, and immunohistochemically express both vimentin and cytokeratins. A 77-year-old man presented with sore throat. The laryngoscope revealed a large polypoid tumor (4×3×4cm) in upper pharynx, and a large biopsy was taken. The biopsy showed malignant epithelioid and spindle tumor cells. There were no apparent transitions between normal epithelial cells and tumor cells. The tumor consisted of malignant epithelioid and spindle cells with marked anaplasia. The tumor showed marked infiltrative features and lymphovascular permiations. Mitotic figures, atypical mitosis, and necrotic areas were present. No apparent features of sarcomas were seen. No rhabdoid cells were seen. Immunohistochemically, the malignant cells were positive for vimentin (3+, diffuse), CK AE1/3 (1+, focal), CK CAM5.2 (1+, diffuse), CK8 (1+, focal), CK18 (1+, focal), CD20 (1+, focal), p53 (3+, 84%), Ki-67 (labeling=94%), CD68 (2+, only focal), and anti-trypsin (2+, only focal). They were negative for CK34BE12, CK5, CK6, CK7, CK14, CK19, CD99, CEA, CA19-9, CA125, EMA, S100 protein, NCAM, NSE, synaptophysin, chromogranin, α-smooth muscle actin, smooth muscle actin, desmin, CD34, CD31, CD45, D2-40, factor-VIII-related antigen, HMB-45, Melan-A, myoglobin, MDM2, CDK4, KIT, and PDGFRA. The author diagnosed this pharyngeal tumor as PT-ES, but the author cannot completely exclude the possibility of sarcomatoid carcinoma. The prognosis of patient was poor; the patient died of carcinomatosis 2years after the manifestation.

Duodenal gangliocytic paraganglioma in a dog: an unusual cause for posthepatic obstructive jaundice

Gangliocytic paraganglioma is a neoplasm with no reported cases in veterinary medicine and rarely described in humans that usually occurs in the second portion of the duodenum. The name is derived from its unique histologic features of carcinoid tumor, paraganglioma, and ganglioneuroma. We report on the clinical and cytohistological features of a duodenal gangliocytic paraganglioma in a miniature poodle dog with intestinal obstruction and severe jaundice. Upper gastrointestinal fibreoptic endoscopy was performed, and cytologic and histologic samples were obtained. Microscopically, a triphasic (epithelioid, spindle, and ganglion-like cells) neoplasm was observed. The dog died and was submitted to necropsy. Grossly, a firm mass was detected in the submucosa of the ampullary region and was associated with regional lymph node enlargement and obstruction of the major duodenal papilla. The present report is the first description of such tumor in animals, which has to be included in the differential diagnosis of intestinal obstructions and posthepatic jaundice in dogs.

Cytokeratin-positive gastrointestinal stromal tumor of biphasic morphology: a case report.

Gastrointestinal stromal tumor (GIST), which is associated with mutations in KIT or a platelet-derived growth factor receptor, alpha polypeptide (PDGFRA), is the most common mesenchymal tumor of the gastrointestinal tract[1]. A definitive diagnosis of GIST is important to ensure administration of effective drugs, such as imatinib mesylate, and immmunohistochemical staining for c-Kit or DOG1 is useful for the diagnosis. According to previous studies, cytokeratin (CK) expression is a rare event in GISTs[2-6], so they can easily be misdiagnosed as other epithelial or epithelioid mesenchymal tumors. In such cases, a diagnosis of GIST can be made when DOG1 immunoreactivity or mutation of KIT or PDGFRA are observed.

Pathologic diagnosis of epithelioid soft tissue tumors

软组织肿瘤的组织学形态较为复杂,除常见的梭形、小圆形、多形性和双相性形态外,不少软组织肿瘤可呈上皮样,易被误诊.熟悉这些上皮样软组织肿瘤的临床病理学特征有助于诊断和鉴别诊断.一、上皮样肉瘤上皮样肉瘤是上皮样软组织肿瘤的代表类型,分为经典型和近端型2种亚型.经典型多发生于10 ～ 40岁问的青少年,中位年龄为26岁,男性多见.好发于手指、手掌、腕部和前臂伸侧面,其次为膝、小腿胫前区、踝、足底和趾,表现为皮肤或皮下单个或多个质地坚实的无痛性小结节,可有溃疡形成,临床上易被误诊为“硬结性溃疡”、“流脓性脓肿”等,久治不愈.近端型患者的平均年龄(40岁)和中位年龄(35.5岁)均较经典型患者大,也以男性多见.肿瘤多发生于躯体的近心端,尤其是盆腔、会阴肛旁区、腹股沟、耻骨区、外生殖区、臀部、大腿和腋窝等处,位于皮下或深部软组织内,体积较经典型大。

Malignant Epithelioid Neoplasm Metastatic to the Lungs With an Unknown Primary Site

Malignant Epithelioid Neoplasm Metastatic to the Lungs With an Unknown Primary Site

Alveolar soft part sarcoma of the uterine cervix: a case report and review of the literature.

Alveolar soft part sarcoma (ASPS) of the uterine cervix is a rare malignancy, and 21 cases have been reported the literature from every language (including our case). Herein, we describe a 17-yearold female patient who presented with active vaginal bleeding. Pelvic examination revealed a 1.6 ×1.0×0.5-cm-sized soft mass protruding from the uterine cervix. The final pathological diagnosis was ASPS of the uterine cervix. Immunohistochemically, tumor cells were strongly nuclear positive for transcription factor E3. The patient remained disease free for 24 months without adjuvant therapy. The prognosis of ASPS in the cervix is considerably better than that of ASPS in soft tissues due to early clinical detection, small size, and resectability. ASPS should be considered in the differential diagnosis of an unusual epithelioid neoplasm showing organoid appearance with mild cytologic atypia and no/rare mitotic figures, particularly in young women. Pathologists should be aware of those unusual locations where ASPS may originate.

Systematic review of response rates of sarcomatoid malignant pleural mesotheliomas in clinical trials

RationaleMalignant pleural mesothelioma is an almost universally fatal malignancy primarily related to asbestos exposure. Based on the differences in immunologic markers and gene expression between histologic subtypes of mesothelioma, and our clinical impression that response rates vary by histology, we decided to examine the reported response rates of mesothelioma subtypes. ObjectivesOur objective was to compare the response rates of sarcomatoid mesotheliomas to the overall response rates in published clinical trials. MethodsWe searched PubMed for “mesothelioma” with the clinical trials filter selected. We included articles published between January 1, 2000 and March 20, 2014 in which subjects received first or second line systemic therapy for malignant pleural mesothelioma. Studies investigating multi-modality therapy including surgery were excluded. Response rates [including 95% confidence intervals (95% CI)] were estimated for the entire patient cohort and then separately for subjects with sarcomatoid tumors. Measurements and main resultsWe reviewed 544 publications of which 41 trials met our inclusion criteria. Eleven of these trials did not include patients with sarcomatoid mesothelioma (27% of eligible studies). The remaining 30 publications included 1475 subjects, 1011 with epithelioid tumors (68.5%), 203 with biphasic tumors (13.8%), 137 with sarcomatoid tumors (9.3%) and 124 with unknown subtypes (8.4%). In total, there were 323 responses (21.9%, complete and partial responses, 95% CI: 16.3, 28.8) to systemic therapy across all histological subtypes. In patients with sarcomatoid tumors (n=137) 19 responses were observed. This accounted for 5.9% of all responses and yields a 13.9% (95% CI: 8.6, 21.6) response rate for patients with sarcomatoid tumors. Multiple biases likely affected this systematic review. ConclusionResponse rates for different histological subtypes of malignant pleural mesothelioma are infrequently reported. Partial and complete responses to systemic therapies appear to be less common among patients with sarcomatoid tumors.

Mucosal melanoma: correlation of clinicopathologic, prognostic, and molecular features.

Although the presence of the t(12;22)(q13;q12) translocation (the defining molecular feature of malignant melanoma of soft parts/clear cell sarcoma) in cutaneous melanoma has been investigated, no large-scale studies have been performed among mucosal melanoma (MucM). In this study we assessed the prevalence of the EWSR1 rearrangement in primary MucM, and analyzed gross and microscopic features with their potential impact on diagnosis and prognosis. Overall, 132 specimens from 84 patients were included. A total of 55 cases had an intramucosal component. Survival of MucMs of the head and neck was associated with two independent factors: size and histology. Tumors more than 3 cm in greatest dimension had an average survival of 12.75 months; those 3 cm or less had an average survival of 38.3 months (P=0.035). Purely epithelioid tumors had an average worse survival of 16.8 months (P=0.028). A cut-off value of 1 mm for Breslow depth provided a statistically significant difference in survival at both 3 and 5 years (P=-0.02) by multivariate analysis in the gynecologic tract. At the molecular level three cases had a EWSR1 rearrangement by fluorescent in-situ hybridization, but only one with an intramucosal component. None of the 58 cases tested by PCR showed the presence of the EWSR1 rearrangement. With the exception of vulvar melanomas, the prognosis of mucosal-associated melanomas was poor and there was a suggestion that spindle morphology may be more favorable. Our study also showed that the EWSR1 rearrangement was very uncommon among MucM. Though 'clear cell sarcoma' is embedded in the sarcoma literature, the synonym 'melanoma of soft parts' has considerable justification in light of our evolving understanding of the molecular genetics in the family of malignant melanomas.