Biomarkers, Tumor ; genetics ; Gastrointestinal Stromal Tumors ; diagnosis ; genetics ; Humans ; Succinate Dehydrogenase ; deficiency ; genetics

Objective: To investigate the clinicopathologic features, immunophenotype and prognosis of CIC-rearranged sarcoma (CRS). Methods: The clinical and pathological data of 10 cases of CRS diagnosed between January 2017 and December 2018 at the Department of Pathology,Fudan University Shanghai Cancer Center were analyzed. Immunohistochemical study and fluorescence in situ hybridization (FISH) were performed. The literature was reviewed. Results: There were five males and five females with a mean age of 28 years (range, 5 to 63 years). Eight tumors developed in the somatic soft tissues, including trunk (n=3),head and neck (n=3),and extremities (n=2). One case each arose in the small intestine and the occipital lobe. The average size was 4.9 cm (range,1.5-8.0 cm). Microscopically,all cases were composed of small to medium-sized round, oval to short spindled cells, showing nodular or lobular architecture, or were arranged in sheets. Compared with Ewing sarcoma, tumor cells of CRS usually showed irregular nuclear outline, coarse chromatin with prominent nucleoli and brisk mitotic activity. Necrosis was present in four cases with one showing geographic necrosis. Immunohistochemically, tumor cells usually showed focal or patch staining of CD99 (9/10),diffuse and strong nuclear expression of WT1 in half cases (2/4),and a high Ki-67 index (median 70%). By FISH, nine cases demonstrated convincing break-apart signal of CIC gene. Follow-up data available in seven cases (mean 12.1 months); of these two patients died of disease (2/7), whereas one patient was alive with unresectable recurrent tumor,the remaining four patients were alive with no evidence of disease. Five patients (5/7) experienced local recurrence and two patients (2/7) developed metastasis. The mean and median intervals to recurrence/metastasis were eight months and four months, respectively. Conclusions CRS is the most common type of EWSR1-negative small round cell sarcoma (SRCS). Although it has clinical and pathological overlapping features with Ewing sarcoma,the prognosis is comparatively poor. Focal or patch staining of CD99 but diffuse staining of WT1 in a case of small RCS should raise the possibility of CRS. FISH assay is required for the final diagnosis.

Objective: To investigate the clinicopathological characteristics and differential diagnosis of lipofibromatosis. Methods: The clinicopathological features and immunohistochemical profiles in 8 cases of lipofibromatosis diagnosed at Fudan University Shanghai Cancer Center from January 2008 to June 2017 were studied. Molecular analysis of β-catenin mutation by Sanger sequencing, NTKR1 and ETV6 rearrangements by FISH were performed. The follow up information was evaluated and the literature was reviewed. Results: There were 4 males and 4 females with a median age of 1.5 years at presentation (range, 3 months-9 years). Tumor arose in the hand (4 cases), foot (2 cases) and trunk (2 cases), manifesting as a painless subcutaneous mass. Two cases were congenital, one with tumor noted at birth and the others shortly after birth. Grossly, the tumors were poorly defined and irregularly shaped, composed predominantly of fatty tissue which was mingled with fibrous element. They ranged from 1 to 5 cm in size (mean, 2.6 cm). Microscopically, they were characterized by variably sized lobules of adipose tissue traversed by fascicles, bundles or trabeculae of proliferative fibroblasts and myofibroblasts, resembling desmoid tumor. In 2 cases, the tumor infiltrated adjacent skeletal muscles. On high power, the spindled fibroblasts and myofibroblasts had a bland appearance with very low mitotic activity (<1/10 HPF). By immunohistochemistry, they showed variable staining of α-SMA, MSA, CD34 and CD99, with negativity for β-catenin, desmin, h-CALD, EMA, ALK, and S-100 protein. Ki-67 index was low (<2%). Molecular analysis showed no mutation of β-catenin gene (0/3), no NTRK1 gene rearrangement (0/3) and no ETV6 gene rearrangement (0/2). Follow up information was available in 6 patients, revealed local recurrence in two and persistent disease in one. Conclusions Lipofibromatosis is a special variant of infantile fibromatosis, which has a predilection for the distal portion of the extremities of neonates and infants and characterized by lobules of adipose tissue traversed by demoid tumor-like fibroblasts and myofibroblasts. However, it differs from desmoid tumor by harboring no mutation of β-catenin gene. Familarity with its clinicopathological characteristics helps the distinction from its morphological mimics.

Objective: To investigate the clinical and pathological features of spindle cell lipoma (SCL) and pleomorphic lipoma (PL) with emphasis on differential diagnosis. Methods: Sixty-five cases of SCL/PL from the archive of Department of Pathology, Fudan University Shanghai Cancer Center, from August of 2006 to June of 2017, were included in the study. Immunohistochemistry by EnVision method, MDM2 gene amplifycation and DDIT3 gene translocation by fluorescence in situ hybridization(FISH) were detected and the literature was reviewed. Results: There were 53 males and 12 females with age ranging from 26 to 82 years (mean, 57 years; median, 59 years). The majority of the lesions occurred in the neck/posterior neck/nuchal region, upper back and shoulder. A small percentage of lesions developed in the extremities, face and trunk, and rarely in the epiglottis, mediastinum, labium majus and perineum. Clinically, the tumor usually manifested as a slowly growing mass or nodule. It was often encapsulated, ranging from 1 to 13 cm (mean, 4.1 cm; median, 3.5 cm) in size. Microscopically, SCL was composed of mature adipose tissue, bland spindle cells and bright eosinophilic "ropey" collagen fibers that varied in proportion. Of 45 SCL, 28 cases (62.2%) were classical, 6 cases (13.3%) were myxoid, 5 cases (11.1%) were fat-poor, 3 cases (6.7%) were fat-free, and 3 cases (6.5%) were pseudoangiomatoid. PL showed similar features as SCL, but was characterized by the presence of scattered floret giant cells. Of 20 PL, 11 cases (55.0%) were classical, 6 cases (30.0%) were mixed SCL/PL, 3 cases (15.0%) were fat-free. Both SCL and PL contained scattered mast cells in the stroma. By immunohistochemistry, the spindle cells in SCL and the floret giant cells in PL showed strong positivity for CD34 (52/52, 100.0%), bcl-2 (24/26, 92.3%) and CD99 (6/6), whereas they were negative for S-100 protein and STAT6. FISH analysis of MDM2 (17 cases) and DDIT3 (4 cases) was negative in all cases. Follow-up information was available in 32 patients (3 to 96 months), with local recurrence in only one patient. Conclusions SCL and PL belong to the same entity but may exhibit morphological disparities. Of note, the fat-poor and fat-free variants are easily mistaken for other mesenchymal tumors. Attention should be paid in their differential diagnosis.

OBJECTIVETo investigate clinicopathologic features, pathologic diagnosis, differential diagnosis and biological behavior of epitheioid myxofibrosarcoma (EMFS).

METHODSThe clinical and pathological data of 10 cases were collected, and microscopic examination and immunostains were performed along with a review of the literatures.

RESULTSThere were 5 males and 5 females with age ranging from 53 to 74 years, and the mean and median age was 63.6 and 62.5 years, respectively. Six cases developed in the extremities, including upper limbs (n=3) and lower limbs (n=3). Three developed in the trunk and 1 case in the mesentery of sigmoid colon. Tumor size ranged from 4.2 to 7.0 cm (mean, 5.3 cm). Most patients presented with painless masses with duration of 1 to 24 months (mean, 8 months). All 10 patients were treated by surgery, with adjunctive chemotherapy and/or radiotherapy in 4 patients and interventional therapy in 1 patient. Histologically, 8 cases were high grade and 2 were intermediate grade. Like the conventional myxofibrosarcomas, all primary tumors presented a multinodular growth pattern consisting of hypocellular myxoid and hypercellular areas. Prominent curvilinear vessels and pseudolipoblasts were observed in the hypocellular myxoid areas. Besides the spindled neoplastic cells, all tumors were characterized by a variable proportion of epithelioid cells with vesicular nuclei, prominent nucleoli and moderate to abundant eosinophilic cytoplasm. They were arranged singly or in small clusters in the myxoid areas, and in compact sheets in the solid areas. The epithelioid component comprised 30% to 90% of the tumors. In addition, areas with resemblance to undifferentiated pleomorphic sarcoma were also noted, especially in the recurrent tumors. Immunohistochemically, tumor cells showed diffuse staining of vimentin in 6 tested cases with focal expression of smooth muscle actin and epithelial membrane antigen in 1 case each. Ki-67 index ranged from 30% to 80% (mean, 58%). Follow-up data (range, 2 to 74 months; mean, 23 months) were available in 10 cases: 4 patients were alive with unresectable or recurrent disease and 6 patients were alive with no evidence of disease. Five patients experienced local recurrence and 2 cases developed metastasis. The median interval to recurrence/metastasis was 7 months (mean, 9 months).

CONCLUSIONSThe presence of epithelioid cells in a myxofibrosarcomatous background portends an aggressive clinical behavior.EMFS should be differentiated from other myxoid sarcomas with epithelioid morphology.

Actins ; metabolism ; Aged ; Biomarkers, Tumor ; metabolism ; Diagnosis, Differential ; Epithelioid Cells ; pathology ; Female ; Fibrosarcoma ; diagnosis ; pathology ; Humans ; Male ; Middle Aged ; Mucin-1 ; metabolism ; Neoplasm Recurrence, Local

OBJECTIVETo further elucidate the clinical and pathologic features of retiform hemangioendothelioma (RH) and its clinical spectrum.

METHODSEight cases of RH were reviewed. The clinicopathologic profiles, immunophenotypes and outcome data were investigated.

RESULTSAll 8 cases occurred in females with a mean age at presentation of 40 years (range, 13-69 years). Five tumors arose in the skin of the head and neck region and lower extremities, two in the long bones and one in the spleen. Clinically, the patients presented with a slowly growing cutaneous plaque or subcutaneous nodule, pain of the upper arm, and dull pain and discomfort in the left hypochondrium respectively. Grossly, the tumor appeared as a non-encapsulated gray-yellowish to tan-brown mass with a mean diameter of 2.6 cm (range, 0.8-5.0 cm). On histology, it was composed of delicate branches of elongated vessels lined by a layer of hobnail or matchstick endothelium, exhibiting a retiform pattern with close resemblance of the normal rete testis. Cords or solid nests of epithelioid cells were noted adjacent to the well-formed vessels. In three cases, dilated vascular spaces with formation of intravascular papillary tufts were observed, features overlapping with Dabska tumor. There was usually marked lymphocytic infiltration in the stroma which was also hyalinized in some cases. One case had regional lymph node metastasis. By immunohistochemistry, all cases consistently expressed endothelial markers, including CD31 (8/8), human coagulation factor VIII (5/8), CD34 (5/7) and D2-40 (1/2). Two of six cases with follow-up information (18-67 months) developed local recurrences, but distant metastasis was not identified.

CONCLUSIONSRH is a distinctive vascular tumor of adulthood characterized by retiform growth of vessels with striking hobnail endothelium. Although the tumor occurs predominantly in the skin, the long bones and the spleen can be occasionally affected. The presence of Dabska tumor-like areas in RH may suggest a morphologic continuum between these two entities, comprising the family of hobnail hemangioendothelioma. Familiarity with the characteristic features of this vascular tumor of intermediate malignancy will help in the differential diagnosis of vascular neoplasms with hobnail endothelium.

Adolescent ; Adult ; Aged ; Biomarkers, Tumor ; Bone Neoplasms ; pathology ; Diagnosis, Differential ; Epithelioid Cells ; pathology ; Female ; Hemangioendothelioma ; pathology ; Humans ; Immunohistochemistry ; Immunophenotyping ; Middle Aged ; Neoplasm Recurrence, Local ; Skin Neoplasms ; pathology ; Splenic Neoplasms ; pathology ; Young Adult

Objective: To investigate the clinicopathologic features, differential diagnosis and biological behavior of pleomorphic leiomyosarcoma (PLMS) and dedifferentiated leiomyosarcoma (DLMS). Methods: Forty-nine cases were collected from November 2007 to December 2016, including eight that diagnosed at Fudan University Shanghai Cancer Center, and 41 consultation cases. The clinical findings and pathologic features were reviewed. Immunophenotype was obtained in 33 cases and follow-up information was available in 38 cases. Results: There were 22 males and 27 females with ages ranging from 24 to 83 years (mean 52.5 years). Fifteen cases occurred in extremities, 14 in deep body cavity, 11 in the trunk, 4 in the head and neck, 2 in the bladder, and 1 each in the inguinal region, perineum and femoral vein, respectively. Tumor sizes ranged from 3 to 30 cm (mean 9.1 cm). The tumors were composed of at least small foci of typical leiomyosarcoma (LMS) and areas of high-grade pleomorphic/undifferentiated sarcoma. The typical LMS component showed the characteristic morphology of smooth muscle differentiation and was low to intermediate grade in most cases. Pleomorphic areas were mainly composed of atypical spindle and polygonal cells admixed with variable large, bizarre atypical cells and multinuclear giant cells, mostly mimicking undifferentiated pleomorphic sarcoma. The pleomorphic and leiomyosarcomatous areas were usually intermixed, but the demarcation may be distinct or gradual in some cases. The classical LMS component was positive for at least one myogenic marker: α-SMA in 97.0%(32/33), desmin in 72.7%(24/33), H-caldesmon in 90.9% (20/22), MSA in 14/16, and calponin in 15/15 of cases. The pleomorphic sarcoma component was reactive for at least one myogenic marker in 87.9% (29/33) of cases, usually showing focal and less intense immunoreactivity than classical LMS component: α-SMA was positive in 81.8%(27/33), desmin in 48.5%(16/33), H-caldesmon in 72.7% (16/22), MSA in 12/16, and calponin in 11/15 of cases. Based on staining for muscle markers in the pleomorphic component, 29 cases were designated as PLMS, 4 as DLMS. Ki-67 index ranged from 15% to 70% (mean 40%). Follow-up data was available in 38 cases (77.6%), of which 11 patients (28.9%) died of disease, 12 patients were alive with unresectable or recurrent disease, 14 patients were alive with no evidence of disease and another one died of unrelated cause. The median disease-free and overall survival was 6 and 10 months respectively. Twelve patients exhibited local recurrence and 11 developed metastases. The median interval to progression was 8 months. Conclusions The identification of areas of typical LMS is crucial for accurate diagnosis of PLMS and DLMS. Both PLMS and DLMS show more aggressive behavior and poorer prognosis than ordinary LMS.

OBJECTIVETo investigate the clinicopathologic characteristics, differential diagnosis and biological behavior of extracardiac rhabdomyoma.

METHODSNine cases of extracardiac rhabdomyoma diagnosed between January of 1997 and July of 2014 were reviewed. The clinical, pathologic and immunohistochemical profiles were evaluated.

RESULTSThere were 5 males and 4 females at diagnosis with age ranging from 2 years and three months to 59 years (mean, 37.6 years). Sites included the head and neck region (7 cases), chest (1 case ) and vagina wall (1 case). Clinically, most cases manifested as a subcutaneous nodule or as a submucosal polypoid lesion with a mean diameter of 3.2 cm. Histologically, 4 were adult-type rhabdomyoma characterized by tightly packed large round or polygonal rhabdomyoblasts with abundant eosinophilic to clear cytoplasm; 3 were myxoid variant of fetal rhabdomyoma composed of immature myofibrils, spindled and primitive mesenchymal cells embedded in a myxoid background, 1 was an intermediate form of fetal rhabdomyoma consisting of densely arranged differentiated myoblasts with little myxoid stroma; 1 was a genital rhabdomyoma composed of elongated or strap-like myoblasts scattered in loose fibrous connective tissue. By immunohistochemistry, they showed diffuse and strong positivity for desmin, MSA and myoglobin with variable expression of myogenin. A case of intermediate type also stained for α-smooth muscle actin. Follow up data (2 months ~ 17 years) showed local recurrence in one patient 6 months after surgery.

CONCLUSIONSRhabdomyoma is a distinctively rare benign mesenchymal tumor showing skeletal muscle differentiation, which may occassionally recur if incompletely excised. Familiarity with its clinical and morphological variants is essential to avoid misdiagnosing this benign lesion as embryonal rhabdomyosarcoma.

Adolescent ; Adult ; Cell Differentiation ; Child ; Child, Preschool ; Desmin ; analysis ; Diagnosis, Differential ; Female ; Head and Neck Neoplasms ; chemistry ; pathology ; Humans ; Immunohistochemistry ; Male ; Mesenchymoma ; pathology ; Middle Aged ; Myogenin ; analysis ; Neoplasm Recurrence, Local ; Rhabdomyoma ; chemistry ; pathology ; Rhabdomyosarcoma, Embryonal ; pathology ; Thoracic Neoplasms ; chemistry ; pathology ; Thoracic Wall ; pathology ; Vaginal Neoplasms ; chemistry ; pathology

Objective:To investigate the clinicopathological features, immunophenotype, diagnosis and differential diagnosis of SRF-rearranged cellular perivascular myoid tumor.Methods:Two cases of SRF-rearranged cellular perivascular myoid tumor diagnosed in the Department of Pathology, Fudan University Shanghai Cancer Center from October 2021 to March 2022 were collected. Immunohistochemical staining, fluorescence in-situ hybridization (FISH) and next-generation sequencing (NGS) were performed, and the literature was reviewed.Results:Case 1, a 3-month-old boy presented with a painless tumor of the scalp, measuring about 2 cm in diameter. Case 2, a 3-year-old girl complained with a painless tumor of the knee, measuring approximately 1.5 cm in diameter. Microscopically, the tumor had a clear boundary and showed multinodular growth. The tumor was mainly composed of spindle cells arranged in long intersecting fascicles associated with thin, slit-like or branching ectatic vessels, focally forming hemangiopericytoma-like appearance. The tumor cells were abundant, but there was no obvious atypia. Mitotic figures (3-4/10 HPF) were noted. H-caldesmon and SMA were positive in both cases. Case 1 showed diffuse and strong positivity for Desmin, and focally for CKpan. Ki-67 proliferation index was 20% and 30%, respectively. FISH displayed NCOA2 gene translocation in case 1 and the RELA gene translocation in case 2. NGS detected the SRF-NCOA2 gene fusion in case 1 and the SRF-RELA gene fusion in case 2. Both patients underwent local excisions. During the follow-up of 5-14 months, case 1 had no local recurrence, while case 2 developed local recurrence 1 year post operatively.Conclusions:SRF-rearranged cellular perivascular myoid tumor is a novel variant of perivascular cell tumor, which tends to occur in children and adolescents. The tumor forms a broad morphologic spectrum ranging from a pericytic pattern to a myoid pattern, and include hybrid tumors with a mixture of pericytic and myoid patterns. Due to its diffuse hypercellularity and increased mitotic figures and smooth muscle-like immunophenotype, the tumor is easy to be misdiagnosed as myogenic sarcomas. The tumor usually pursues a benign clinical course and rare cases may locally recur.

Objective: To investigate the clinical pathological features, pathological diagnosis and differential diagnosis of hybrid schwannoma/perineurioma. Methods: The clinicopathological data of 35 cases were collected at Fudan University Shanghai Cancer Center, from October 2010 to August 2017; morphological observation and immunohistochemical staining were performed, and the literatures were also reviewed. Results: There were 7 males and 28 females (male∶female=1∶4), patients with onset age ranging from 3 to 81 years(mean=36 years). Of 35 tumors, 11 cases occurred in the head and neck, 10 in the extremities, 9 in the trunk, 4 in the intestine, and 1 in the labiamajora, respectively. Clinically, most patients presented as a slowly growing dermal nodule, sometimes associated with pain. The duration of symptoms ranged from 1 month to 20 years before excision. Tumor size ranged from 0.8 cm to 6.0 cm (mean=2.6 cm). Microscopically, the tumors were usually well circumscribed but unencapsulated. At low power, most tumors were located in the dermis or subcutis, and several cases in the submucosal tissues. The tumors were composed of fascicular, storiform or whorled growth of closely intermixed plump spindle cells and slender spindle cells. The plump spindle cells had ill-defined eosinophilic cytoplasm with larger tapered or wavy nuclei, whereas the slender spindle cells had comparatively delicate nuclei with elongated cytoplasmic processes. Tumor cells had no obvious atypia, and mitoses were rare. Scattered large cells with degenerative nuclear atypia were seen in some cases. By immunohistochemistry, most of plump spindle cells showed strong staining of S-100 protein(35/35) and SOX10(8/9), whereas slender spindle cells stained variably for epithelial membrane antigen(31/35), CD34(32/33), Claudin-1 (15/15) and GLUT-1(8/8). Ki-67 proliferation index were all less than 5%. Follow-up data available in 16 patients (range 4 to 72 months; mean=46 months) were all free of disease, and one case developed local recurrence. Conclusions Hybrid schwannoma/perineuriomaisa benign nerve sheath tumor that typically manifests as a dermaland subcutaneous tumor, less frequently may affect uncommon sites such as the nasal cavity, the gastro-intestinal tract, and the external genital areas. The tumors consisted of intimately admixed plump-spindled schwannian cells and slender-spindled perineurial cells showing dual differentiation of strong S-100 protein and SOX10 expression in the former component and variable immunoreactivity of epithelial membrane antigen, Claudin-1 and CD34 in the latter. It should be aware of the possibility of potentially misinterpretation of hybrid schwannoma/perineurioma as dermatofibrosarcoma protuberans and solitary fibrous tumor and so on.