Abstract: Sclerosingepithelioidfibrosarcoma (SEF) is a rare neoplasm mostly arising in limbs and limb girdles, with a high rate of recurrence. Herein, we describe a rare case of primary SEF in the chest wall with concurrent breast cancer. A 41-year-old female was found to have an asymptomatic mass in the upper chest wall on magnetic resonance imaging that was performed for breast cancer. Histology of the resected tumor showed features of SEF, with epithelioid cells arranged in nests or a retiform pattern within a sclerosing stroma. By immunohistochemistry, the tumor cells showed staining for vimentin and epithelial membrane antigen, and were negative for cytokeratin. EWSR1 rearrangement was found by fluorescence in situ hybridization. She is currently disease free at 29-month follow-up. We herein report a rare case of SEF with concurrent breast cancer. The top differential diagnosis was between SEF and metastatic breast cancer. The distinction is important for implications in tumor staging and clini- cal management.
The authors present two cases of primary sclerosingepithelioidfibrosarcoma (SEF) of the kidney. Both patients had a mass in the upper part of the left kidney without any primary extrarenal neoplastic lesions. Grossly, the tumors were solid masses both measuring 7.5 cm in the greatest diameter. Histologically, one of the lesions exhibited a predominantly lobular growth of round or oval small uniform epithelioid cells in variable cellularity. Circular zones of crowded tumor cells alternating with hypocellular collagenous tissue in a concentric fashion around entrapped native renal tubules were distinctive. The second case was distinctive with significant cytological atypia in the neoplastic cells and prominent reactive proliferations in the trapped renal tubules. Immunohistochemically, vimentin, bcl-2 and MUC4 were diffusely positive in both. They were negative for S-100 protein, CD34, and desmin, whereas CD99 were positive in one lesion. Fluorescence in situ hybridization assay using dual staining probes detected EWSR1-CREB3L1 fusion in each lesion, which is characteristic molecular findings of SEF. One patient presented widespread distant metastases at the time of diagnosis. In the other, no tumor deposits were detected other than primary. Both patients have been alive with 30 and 10 month follow-ups, respectively. These tumors are 6th and 7th cases of primary renal SEF in the literature confirmed by FISH study, which exhibit unique and
Abstract: Sclerosingepithelioidfibrosarcoma (SEF) is a clinicopathologically distinct variant of fibrosarcoma that is capable of recurrence and metastasis. Awareness of imaging features and histopathologic characteristics will be helpful for differential diagnosis from other common tumors. Here, we report a case of SEF metastasizing to the pancreas as a solitary mass mimicking primary pancreatic cancer, and summarize the reported cases with FDG PET/CT from the literature (n=4). PET/CT showed abnormal FDG accumulation (n=2), mild FDG uptake (n=1), or photopenic (n=1). The FDG PET/CT features are closely related to histopathologic characteristics regarding its dif- ferentiation and aggressiveness.
Meis-Kindblom et al. in 1995  as a proliferation of neo- plastic oval or round cells arranged in cords or a nest-like distribution against a collagen background with prominent features of sclerosis. This variant of fibrosarcoma has a typi- cally low-grade histological appearance with a low mitotic count and lacks the presence of necrosis. When present, the carcinoma-like infiltrating growth pattern in SEF dif- ferentiates this malignancy from other epithelioid tumours. Alternatively, when these features are absent, the deceptively bland morphology compounds the difficulty in distinguish- ing fibrosarcoma from other fibrous growths (i.e. desmoid tumours, nodular fasciitis). SEF typically originates in the lower extremities with a high propensity for local recurrence after surgical resection and eventual metastasis to the lungs and bones . The rarity of this disease  and the chal- lenges of establishing a positive histological diagnosis have
A total of 46 DTF tissue sections and 49 other lesion types (controls) were analyzed, with their clinicopathological fea- tures summarized in Table 1. Among the 46 DTF patients, 18 (39.1%) were male and 28 (60.9%) were female, with a mean age of 36 years (range 15–65 years). With regard to DTF localization, 16 (34.8%) were located in the abdominal wall, 15 (32.6%) in the abdominal cavity, 7 (15.2%) in the limbs, 7 (15.2%) in the back, chest and hips, and 1 (2.2%) in the breast. As compared to the control lesions used in this study, a higher frequency of DTF lesions was found among women. Among the control samples, nodular fasci- itis was primarily presented in the limbs (73.3%), and all GIST and sclerosingepithelioidfibrosarcoma (SEF) occurred at the abdominal cavity.
cells was pseudopapillary architecture signifi- cantly conspicuous except for the nested-and- solid area. Pseudopapillary structure with superimposed relatively uniform epithelioid or oval tumor cells stemmed from the fact that the stratified cells far away from capillaries failed in adherence and hence separated and fell off. This prominent pseduopapillary appearance is extremely rare, and has barely described by two reports up to now [1, 4]. Immuno- histochemically, the vast majority of the tumor cells show a consistent immunophenotype, with strong expression of S100 protein and absent expression of HMB-45, Melan-A and tyrosinase, indicating a deficiency in melano- cytic differentiation. The positive expression of other neuroectodermal markers, such as CD56, NSE, synaptophysin, can be demonstrated in some cases . Although GNET shares a com- pelling genetic feature with CCS in soft part, with a presence of EWS-ATF1 or EWS-CREB1 fusion, that would not be conclusive proof of a link between these two tumors . Because EWS, a “promiscuous” gene, seems to fuse with many different partner genes and the translocation has been identified in diverse sar- coma as well as some non-mesenchymal tumors. Take the former for example, they include CCS of soft tissue, GENT, myxoid lipo- sarcoma, extraskeletal myxoid chondrosarco- ma, angiomatoid fibrous histocytoma, Ewing sarcoma, sclerosingepithelioidfibrosarcoma, low-grade fibromyxoid sarcoma and so on . Consistently, there existed EWS rearrangement by FISH in our case. But the probe we used didn’t reveal the partner gene juxtaposed with EWS. However, an unverified speculation needs a further investigation that the cases with a sig- nificant pseudopapillary architecture in mor- phology tend to be EWS-CREB fusion rather than EWS-ATF1 according to the limited report- ed literature [1, 10]. And furthermore, at the ultrastructural level, melanosomes were not observed in any reported cases, and a distinc- tive neural differentiation was confirmed by Stockman et al, which possessing multiple interdigitating cell process containing dense core granules and synaptic bulbs-like vesicles suggesting tumor’s origination from autonomic nervous system-related primitive cell of neural crest derivation [1, 6]. So it is reasonable to substitute the designation “malignant gastroin- tenstinal neuroectodermal tumor” (GNET) for the term “clear cell sarcoma” in the gastroin- testinal tract.
The histopathologic examination of the specimen showed cross-section of vessel, showing a sheet- like proliferation of the epithelioid endothelial cells in the lumen, which was almost occluded, with focal rupture of the media. There was diffuse inflammatory cell infiltration composed mainly of small lymphocytes along with scattered eosinophils and an occasional giant cell.A close histologic differential diagnosis was giant cell arteritis with neovacularisation secondary to organisation of thrombus in view of the presence of inflammatory cells and giant cell, though there was absence of granulomas. As the histologic differentiation was difficult,
extensive hemorrhage were observed on the serosa. One 0.8-cm myoma-like nodule with a well-demarcated mar- gin was found within the myometrium. No thickening of the endometrium was seen. Histologically, the uterine corpus revealed adenomyosis throughout the entire myometrium, extending to the serosal surface (Figure 1A). A PEComa-NOS, composed of ill-defined spindle cell fascicles, was found to mainly be distributed around the adenomyosis foci (Figure 1A). In contrast to the deeply eosinophilic hypertrophic myometrium, the spindle cells had clear to lightly eosinophilic cytoplasm. Their nuclei were oval to spindle-shaped and uniform, with no mitotic activity. The endometrial stroma of ade- nomyosis was focally replaced by the PEComa. LAM, characterized by poorly defined nodular proliferation of spindle cell fascicles with many tongue-like protrusions in dilated vascular spaces, was also noted in the myome- trium (Figure 1B). Tumor cells of the PEComa and LAM showed diffuse immunoreactivity with smooth muscle actin (SMA) and progesterone receptor (PR) (Figure 1D, E, G, H). HMB-45 and desmin were expressed to a lesser degree. They were negative for CD10 and estrogen receptor (ER). The myoma-like nod- ule was a sclerosing PEComa with uniform epithelioid cells in a hyalinized extracellular matrix (Figure 1C). It showed focal HMB-45, PR, SMA, and desmin expres- sions (Figure 1F, I). Neither CD10 nor ER expression was observed. Ovarian and pelvic tissues, taken during the first surgery, respectively revealed an endometriotic cyst and endometriosis.
Vanderstichel 2006), and most cerebral tumours are either metastatic angiosarcomas or hamarto- mas (Cordy 1990). A review of the EHE literature reveals only one case of intracranial involvement in animals, in which a calf brain exhibited features which resembled epithelioid and spindle cell vari- ants of haemangioendothelioma (HE) (Finnie et al. 1993). Other reports of rare variants of HE in- clude kaposiform HE in a dog (Vincek et al. 2004) and cow (Pires et al. 2009), epithelioid HE in the dermis-subcutis of a dog (Warren and Summers 2007) and retiform HE in two dogs (Lombardini and Summers 2013). To the best of our knowledge, intracranial occurrence in dogs has not yet been reported. Furthermore, the gross findings of EHE in the central nervous system of animals have not been documented.
The gene hSNF/INI1/SMARCB1/BAF47 is a putative tumor suppressor gene expressed in all normal cells. The inactivation of SMARCB1 has been observed in malignant rhabdoid tumors (MRT), childhood atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system (CNS), epithelioid sarcoma , subsets of col- lecting duct carcinoma  and epithelioid malignant peripheral nerve sheath tumor (MPNST) , renal medullary carcinoma  and undifferentiated pediatric sarcomas , etc. The loss of SMARCB1 nuclear expression is of diagnostic value for renal or extra- renal MRT and AT/RT .
The features which served as common denominators in these reports were (in contrast to other soft tissue sarcomas with epithelioid morphology simulating CCS), multiple smaller nucleoli [2-6]. These features were observed in our cases too [Table/Fig-4,5]. Intranuclear cytoplasmic inclusions and cytoplasmic pigment have also been described though, not present in our cases . A rare granular cell variant has also been recognised . Tong TR et al., have reported a case of CCS with cells showing marked cellular cohesion and
IgG4-positive plasma cells. Since then, a series of such lesions outside the pancreas have been reported, such as sclerosing cholangitis, mediastinal fibrosis, interstitial pneumonia, tubulointerstitial nephritis and chronic scleros- ing sialadenitis [1, 5]. These lesions can be alone or as a part of a systemic disease. They can occur with pancreatic lesions synchronous- ly or metachronously, or even in the absence of pancreatic lesions . The etiology and patho- genesis of IgG4-related sclerosing disease remains unclear. IgG4 is the most rare subtype of IgG, only representing about 3%~6% of the serum total IgG under normal circumstances . The elevation of serum IgG4 level and the presence of abundant IgG4-positive plasma cells in the lesions indicate that IgG4 may play an important role in the pathogenesis of the disease. CSS, mostly affecting the submandib- ular gland, is a benign tumor-like lesion pre- senting with firm mass and well-defined bound- ary. Clinically, it can be sometimes difficult to distinguish from neoplasm. CSS can occur uni- laterally or bilaterally, with a predominance in male and middle-aged to elderly patients . The histological features of CSS are similar to lymphoplasmacytic sclerosing pancreatitis. Immunohistochemical staining shows diffuse infiltration of large numbers of IgG4-positive plasma cells. Recently, CSS has been proposed to be a member of the IgG4-related sclerosing disease group . From three large scale of researches [9-11], a total of 29 cases of IgG4- related CSS were described. These were 16 males and 13 females, with mean age of 61 years old. Two patients presented with autoim- mune disease (Graves disease and Hashimoto thyroiditis respectively). Eight patients had IgG4-related sclerosing disease outside sali- vary glands, 3 of whom with multiple organs involved. Morphological features of the 29 patients were similar. Of all the patients, the mean number of IgG4-positive plasma cell per HPF was 162; the ratio of the IgG4 to IgG- positive plasma cells was 0.79.
was strongly reactive with reduplicated basal lamina of them (Fig. 3b). By contrast, they were completely negative for cytokeratins (CKs) (AE1/AE3, diluted 1:1; Dako; & Cam5.2, diluted 1:10; Becton Dickinson Immunocytometry Systems, San Jose, CA, USA), EMA (diluted 1:1; Dako), α- smooth muscle actin (α-SMA, diluted 1:1; Dako), desmin (diluted 1:1; Dako), CD10 (diluted 1:1; Dako), CD31 (diluted 1:1; Dako), CD34 (diluted 1:1; Dako), CD68 (KP-1, diluted 1:200; Dako), p63 (diluted 1:200; Dako), Melan A (diluted 1:50; Dako), HMB45 (diluted 1:100; Dako), CDK4 (diluted 1:50; Santa Cruz Biotechnology, Dallas, TX, USA), MDM2 (diluted 1:200; Invitrogen, Carlsbad, CA, USA) and p53 (diluted 1:1,000; Dako). The immunohistochemical profiles of these epithelioid cells in the present case are summarized in Table 2. In addition, the Ki67 (MIB-1, di- luted 1:1; Dako) labeling index was much less than 1% in the proliferating tumor cells. Finally, immunohistochemical staining of S-100 protein could not detect any reactive ele- ments, including contiguous native perineurium of the per- ipheral nerve, in this encapsulated vessel-like structure (Fig. 3a). All of the immunohistochemical stainings were conducted using the Dako Envision kit (Dako) in accord- ance with the manufacturer’ s instructions [5–8].
Microscopically, GP has three characteristic components: epithelioid cells, ganglion-like cells, and spindle cells. The portion of this three components varies widely from case to case [6, 16], which pose a challenge for pathologists to make a definite diagnosis especially in a small biopsy. We can assume, if this tumor display a predominance of one or two of above compo- nents, various differential diagnoses, including carcinoid, paraganglioma, carcinoma, schwan- noma or ganglioneuroma, should be consid- ered. In this case, the epithelioid cells arranged in various histological structures, including Zellballen, papillary, cystic and microcystic pat- tern. The Zellballen structure showed variable nest like carcinoid or paraganglioma. The papil- lary structure was first mentioned by Burke and Helwig . This structure brought us to think of pulmonary sclerosing haemangioma which is almost exclusively located in lung parenchyma. Of the 100 cases of pulmonary sclerosing hem- angioma reported by Devouassoux-Shishebo- ran et al, only one was described as an endo- bronchial polyp . However, pulmonary GP appears not to involve adjacent lung parenchy- ma . The cystic pattern has not been men- tioned in the literature. However, some authors had described pseudoglandular structures which seemed to have some similarity to the microcystic structure we described [18-20]. Figure 1. Chest CT scan showing an endobronchial
Interspersed were large cells with abundant cytoplasm, vesicular nuclear chromatin and prominent nucleoli. A wide panel of IHC makers was performed to sort out a diagnosis from an equally wide range of differentials, including metastasis from a poorly differentiated carci- noma, a rhabdomyosarcoma, a melanoma, an epithelioid leiomyosarcoma, an epithelioid angiosarcoma, an epithe- lioid malignant peripheral nerve sheath tumor (MPNST), an epithelioid gastrointestinal stromal tumor (GIST), a conventional ES, an anaplastic large cell lymphoma (ALCL), a synovial sarcoma, an extra-renal rhabdoid tumor and a mesothelioma. In the clinico-radiologic met- astatic work-up, no definite mass was identified in the solid organs as well as in the gastrointestinal (GI) tract. In addition, CEA levels were found to be normal. No glandu- lar or squamoid areas were seen in the tumor. Further, on IHC, lack of CK20 and CEA expression made a possibility of a metastatic adenocarcinoma from the GI tract as less likely. CD 34 positivity further substantiated a diagnosis of an ES over a carcinoma, as well as a synovial sarcoma, the latter which is known to express epithelial and mesen- chymal markers [5,6]. Apart from this dual immunoreac- tivity, no biphasic tumor cell pattern was noted. Lack of S- 100 and HMB-45 ruled out the possibilities of an epithe- lioid MPNST and a melanoma. Desmin was found to be focally positive as has been seen by Guillou et al in 62.5% of their cases of proximal-type ES . Possibility of an epi- thelioid rhabdomyosarcoma was discarded considering strong immunoreactvity for CK, CK7 and EMA along with
other hand, simultaneous occurrence of bladder fibrosarcoma with uroliths inside it has not been reported in dog until now. The present report characterizes a rare canine bladder fibrosarcoma with a urolith spontaneously that the mentioned tumor and urolith were removed surgically and the tumor was diagnosed pathologically. Post-operation monitoring was revealed that no sign of recurrence or metastasis of the tumor was found in the treated dog within 3 months.
Composite infantile myofibromatosis of the scalp with several distinct histopathological features including myofibroma, hemangiopericytoma, and fibrosarcoma have been described in newborns . An infantile rhabdomyo- fibrosarcoma that lies intermediately between rhabdomyo- sarcoma and infantile fibrosarcoma in terms of clinical presentation, immunohistochemistry, behavior, morph- ology, and ultrastructural features has been reported in a 26-month-old girl .
Bone marrow aspiration smears were hypercellular in 21 (44.6%), normocellular in 14 (29.78%), hypocellular in 9 (19.4%) cases and in three (6.38%) cases it was aparticulate. The aspiration cytology smears revealed epithelioid cell granulomas in 7 (14.8%) cases. Erythropoiesis was normoblastic in 44(93.6%) and megaloblastoid in 3(6.38%) cases. Myeloid series and megakaryocytes were unremarkable. There was prominence of lymphocytes and plasma cells in 62 % cases and histiocytic aggregates in 19% cases. Acid fast bacilli were demonstrated in one case (Fig-1. E). Stains for fungi were negative. The details of the bone marrow aspiration
From a diagnostic viewpoint, IMT-RA needs to be dif- ferentiated from a large group of tumors that manifest epithelioid features. Immunohistochemistry is greatly helpful in this process. Nuclear membrane staining of ALK is a unique immunophenotype of IMT-RA, which is observed in 82% (9/11) of cases. Unexplainably, a cytoplasmic pattern is also detected in 18% (2/11) of cases. In addition, the neoplasms display varied expres- sion of desmin (89%, 8/9), CD30 (71%, 5/7), SMA (50%, 4/8), and cytokeratin (25%, 2/8), while EMA, S100, CD117, Myf4, myogenin, caldesmin, and HMB45 expres- sion is consistently negative. Therefore, IMT-RAs could be easily distinguished from poorly differentiated carcin- oma, malignant melanoma, epithelioid gastrointestinal stromal tumor, epithelioid solitary fibrous tumor , Table 1 Clinical features of 11 cases of inflammatory myofibroblastic tumor with RANBP2-ALK gene fusion