EWSR1-SMAD3 rearranged fibroblastic tumor: Case series and review.

We report the largest series to date (N = 6) of EWSR1-SMAD3 rearranged fibroblastic tumor. Initially described in 2018, the tumor features a marked female predominance (F:M, 5:1, mean age 44-years, median age 45.5 years; range 27-57), with most cases (5/6, 83%) arising in acral locations (4 on foot/toe, 1 on hand). One case presented on the lower extremity. The lesions presented as nodules and were composed of short, variably cellular, intersecting fascicles of uniform spindled cells in a collagenous to myxoid stroma. In four cases, the tumor abutted the epidermis without a grenz zone. In one case, there was an abrupt transition to a central, acellular hyalinized area. Two other cases had admixed smaller collagenous areas, reminiscent of collagen rosettes. One had a concentric arrangement of tumor cells around blood vessels. Mitotic activity was low (<1/10 HPFs). All were positive for ERG by immunohistochemistry and negative for CD34 (6/6). An EWSR1-SMAD3 fusion was identified in three cases tested by next-generation sequencing (3/3). Rearrangement of EWSR1 by fluorescence in situ hybridization was showed in 1/1 case. Our series reaffirms prior findings and expands the known histopathologic spectrum of this emerging entity.

Cutaneous pleomorphic fibromas arising in patients with germline TP53 mutations.

Pleomorphic fibromas are rare benign cutaneous neoplasms associated with deletion/loss of chromosomes 13q and 17p, where RB1 and TP53 are located, respectively. Herein, we report five cases of pleomorphic fibroma arising in patients with germline TP53 mutations, suggesting a potential link with Li-Fraumeni syndrome. All three patients were female and young (mean age 27) with a strong personal and/or family oncologic history and confirmed pathogenic germline TP53 mutations. In two patients, multiple pleomorphic fibromas were diagnosed. Clinically, the lesions arose at various cutaneous sites and were small (≤2 cm) and raised (4/5). Histopathologically, the tumors were paucicellular, composed of atypical spindled to stellate cells with hyperchromatic and variably pleomorphic nuclei. Mitotic activity was exceedingly low, although rare atypical mitotic figures were seen in one case. Immunohistochemically, the tumor cells were diffusely positive for p16 (3/3) and showed loss of Rb expression (5/5). All cases showed aberrant p53 expression (overexpression in 4, complete loss in 1). The tumors have followed a benign clinical course with no evidence of progression or recurrence. In conclusion, the development of multiple pleomorphic fibromas in a young patient may be a clue to an underlying genetic cancer syndrome involving TP53.

[Value of MDM2, CDK4 and SATB2 immunohistochemistry in histologic diagnosis of low-grade osteosarcoma].

OBJECTIVE: To investigate the value of combined application of MDM2, CDK4 and SATB2 immunohistochemistry in pathological diagnosis of low-grade osteosarcoma. METHODS: Forty-seven cases of low grade osteosarcoma, including low grade central osteosarcoma (n=20) and parosteal osteosarcoma (n=27), were selected from Shanghai Jiaotong University Affiliated the Sixth People's Hospital. The clinical, radiography and histopathology were reviewed. The sensitivity and specificity of MDM2, CDK4 and SATB2 immunohistochemistry in the diagnosis of low-grade osteosarcoma were assessed along with an evaluation of their expressions in fibrous dysplasia, desmoplastic fibroma, low-grade fibrosarcoma and other fibrous tumors. RESULTS: Low-grade osteosarcoma had protracted clinical course, occurring mostly in elder adults and mainly involving long bones. Radiographic studies showed that low-grade central osteosarcoma had a mainly malignant lytic presentation, however about 5/18 of tumors overlapping with intermediate and benign bone diseases, while parosteal osteosarcoma was characterized by a densely sclerotic malignant appearance. Histologically, low-grade osteosarcomas were characterized by well-differentiated spindle tumor cells, various mature tumor bones and an aggressive growth pattern. The positive expression rates of MDM2 and CDK4 in low-grade osteosarcoma were 74.5% and 55.3%, respectively. Eighty-three percent of low-grade osteosarcoma expressed one or both markers. Low-grade osteosarcoma and fibrous dysplasia were both positive for SATB2, while desmoplastic fibroma, low-grade fibrosacoma and other fibrous tumors were negative for SATB2. CONCLUSIONS: Accurate diagnosis of low-grade osteosarcoma should be based on combination of clinical presentation, imaging and histopathology, with immunohistochemistry as a diagnostic adjunct. Positive immunostaining for CDK4 and/or MDM2 supports the diagnosis of low-grade osteosarcoma, but the negative one does not rule out such lesion. The negative expression of SATB2 is helpful to exclude fibrous tumors originating from bone with the exception of fibrous dysplasia.

Cutaneous clear cell neoplasms: a histopathological reappraisal.

Cutaneous clear cell neoplasms represent a heterogenous group of several primary and metastatic tumors with diverse histogenesis. Tumors with widespread clear cell change can seem strikingly similar under the microscope resulting in diagnostic difficulties. Although most cases are idiopathic, intracytoplasmic accumulation, artifact of tissue processing, and degenerative phenomenon have been cited as possible causes of clear cell change. An awareness of the various entities demonstrating this attribute, judicious use of ancillary techniques, and knowledge of the clinical setting are crucial to the accurate diagnosis. This review details the histological features of clear cell neoplasms of the skin with particular emphasis on the discriminating features.

[Clinicopathologic features of calcifying fibrous tumor with reappraisal of its histogenesis].

OBJECTIVE: To study the clinicopathologic features and histogenesis of calcifying fibrous tumor (CFT). METHODS: The clinical manifestations, histopathologic characteristics and immunophenotype were analyzed in 11 cases of CFT. RESULTS: The male-to-female ratio was 5:6, with a mean age of 38 years and age range of 25 to 52 years. The sites of involvement included abdominopelvic cavity (n=6), soft tissue (n=4) and scrotum (n=1). Most patients presented with a gradually enlarging and painless mass. Nearly half of the cases were associated with other diseases or history of inflammation, trauma or surgical intervention. One third of the tumors represented incidental findings and showed no recurrence after resection. Imaging revealed a solitary solid soft tissue mass or multiple nodules with clear borders and associated high-density calcifications. Macroscopically, the tumors were well-circumscribed but non-encapsulated. They ranged from 0.5 to 20.0 cm in diameter and were tan-greyish, round to oval, lobulated or irregular and solid with rubbery consistency. The cut surface was whitish to tan-yellowish, gritty and showed scattered spotty yellowish discoloration corresponding to the foci of dystrophic calcifications. Histologically, CFT was composed of hyalinized fibrous tissue and thickened vessel walls with interspersed bland spindly fibroblastic cells, scattered psammomatous calcifications, dystrophic calcification and lymphoplasmacytic infiltration. In addition, focal cloak-like polymorph infiltration at the tumor periphery and entrapment of adipocytes and nerves were demonstrated in some cases. Foci resembling solitary fibrous tumor, fibromatosis, keloid or inflammatory myofibroblastic tumor were observed. Immunohistochemical study showed that the tumor cells were diffusely positive for vimentin and focally positive for CD34, factor VIII-related antigen and beta-catenin. The admixed plasma cells were notably IgG positive, with more than 50% being IgG4 positive. CONCLUSIONS: CFT has characteristic histopathologic manifestations and shows morphologic and immunohistochemical overlaps with known IgG4-related sclerosing diseases. It is possible that CFT may represent another example of IgG4-related diseases. It often runs a benign clinical course, with rare recurrence after surgical resection. Previous inflammation and trauma may be the precipitating factors of CFT.

[Fibrolamellar carcinoma of the liver].

The paper presents the data available in the literature and theauthors' own case of hepatic fibrolamellar carcinoma developing in a 49-year-old male patient. A complex morphological (histological and immunohistochemical) study has shown that the tumor is presented by trabecular, alveolar, and glandular structures separated by connective tissue interlayers. The tumor cells showed a positive reaction with cytokeratins 7, 8,18, 19, vimentin, synaptophysin, alpha-fetoprotein, carcinoembryonic antigen, and CA 19-9.

Superficial CD34 positive fibroblastic tumor: report of three cases and review of the literature.

Superficial CD34 positive fibroblastic tumor (SCPFT) is a recently recognized, unique neoplasm with distinctive histomorphological features such as high pleomorphism, low mitotic rate, and diffuse CD34 reactivity. Hereby we present three cases of our experience with clinicopathological, morphological, and immunohistochemical characteristics. The patients were a 31-year-old female, 53-year-old female, and 33-year-old male. The tumors were all superficially located; left forearm, medial aspect of the left ankle, and left thigh, respectively. Histomorphologically they had expansile and focal infiltrative growth pattern consisting of highly pleomorphic spindle cells with intranuclear inclusions, yet low mitotic rate. Tumoral cells showed strong and diffuse reactivity for CD34. One of our cases showed focal and weak reactivity for pancytokeratin. Unlike the other two tumors, one case was positive for desmin. During the clinical follow-up, one case showed local recurrence four times. SCPFT is a newly recognized, borderline mesenchymal neoplasm of soft tissues that can show local recurrence or even rarely metastasize. To the best of our knowledge, this three case series is the first to be reported from Turkey. Our aim to report these three cases was to make contribution to the literature about this rare entity and increase awareness.

Clinicopathologic Study of Calcifying Fibrous Tumor Emphasizing Different Anatomical Distribution and Favorable Prognosis.

AIMS: Calcifying fibrous tumor (CFT) is a very rare begin fibroblastic tumor featuring a widely anatomical distribution and may mimic various spindle cell tumors. Misdiagnosis and hence mistreatment are likely caused due to unfamiliarity to clinicians or junior pathologists. We collected a relatively large series of CFTs in our institution aiming at further summarizing their clinicopathologic features in Chinese patients and discussing the diagnosis and differential diagnosis in clinical practice. METHODS: Clinicopathologic data of 22 CFTs were retrospectively reviewed. Histologic features were reevaluated and summarized. Immunostaining markers include CD34, SMA, Desmin, keratin, S100, ALK1, CD117, IgG, IgG4, and Ki-67. Follow-up of all cases was performed. RESULTS: 22 CFTs include gastric (n=8), pulmonary (n=2), hepatic (n=2), cervical (n=1), appendiceal (n=1), esophageal (n=1), retroperitoneal (n=1), intra-abdominal (n=1), diaphragmatic (n=1), spermatic cord and scrotum (n=1), anconeal (n=1), mesenteric (n=1), and omental (n=1) lesions. Coexisting hepatocellular carcinoma, pancreatic carcinoma, pheochromocytoma, Castleman disease, and leiomyoma of the uterus and other metabolic or functional disorders were also appreciated. CFT histologically features spindle cells embedded dense hyalinized stroma with scattered psammomatous calcifications and lymphoplasmacytic infiltration and immunohistochemically for CD34. None of any individuals die of CFT per se. CONCLUSION: Our study discloses that CFT is a bona fide benign fibroblastic lesion, regardless of its developing location. Involvement of digestive tract seems much more common in the Chinese population. Awareness of the clinicopathologic characteristics of this rare entity and its mimickers contribute to avoiding misdiagnosis and mistreatment in clinical practice.

Paratesticular Fibrous Pseudotumor: A New Entity of IgG4-Related Disease?

INTRODUCTION: Paratesticular fibrous pseudotumor (PFP) represents a benign tumor-like lesion confined to intrascrotal, paratesticular areas. Due to its rarity, only less than 200 cases have been reported to date, of which both pathogenesis and clinical management are little understood. Recently, PFP has been postulated to be among the spectrum of so-called immunoglobulin G4-related diseases (IgG4-RD). Here we describe a case of PFP focusing on the clinical, morphological features and the utility of immunohistochemistry to support the theory that PFP might be a potential member of IgG4-RD family. CASE PRESENTATION: A 41-year-old man presented with a slowly growing, right intrascrotal mass An MRI scan revealed a diffuse-proliferative nodular mass around the paratesticular area. The patient underwent right orchiectomy and a diffuse multinodular tumor with testicular compression was discovered without intratesticular infiltration. Postoperatively, the patient has been well for 2 years up to the recent follow up. On histological examination, the lesion consisted of hyalinized fibrotic tissue with storiform patterns. There were scattered germinal centers; lymphocytic vasculitis was also noted. The immunoglobulin G4 staining showed infiltration of positive plasma cells with highest count 52 per high-power field, whereas the mixed Kappa and Lambda immunoglobulin light chain expression indicated the polyclonality of the plasma cell population. CONCLUSIONS: The morphological and immunohistochemical features in our case support the theory of PFP being part of IgG4-RD. Familiarity to this tumor-like lesion is crucial, since it may respond to corticosteroid therapy, which may save patients from more aggressive surgical procedures.

Solitary fibrous tumor on needle biopsy and transurethral resection of the prostate: a clinicopathologic study of 13 cases.

One of the least commonly encountered spindle cell tumors seen on prostatic needle biopsy or transurethral resection (TUR) of the prostate is solitary fibrous tumor (SFT). We studied 13 cases of SFTs identified on either prostate needle biopsy (n=9) or TUR of the prostate (n=4). Mean patient age at diagnosis was 63 years (range: 46 to 75 y; median: 65 y). Twelve men presented with urinary tract symptoms and 1 patient was biopsied during work-up of bone metastases. Ten cases were SFTs originating in the prostate, 2 cases arose between the prostate and rectum extending into the prostate (n=2), and 1 case was a pelvic mass without infiltration of the prostate. In 9 cases, a complete tumor resection was attempted by cystoprostatectomy (n=2), radical prostatectomy (n=4), pelvic exenteration (n=2), or pelvic tumor resection (n=1). Enucleation (n=1) and TUR (n=1) were performed in 2 other cases. Tumor sizes ranged from 8.5 to 15 cm in 7 radically resected cases. Mitotic rates were 3 to 5 per 10 high power fields in 5 cases, with the remaining cases having either rare (n=4) or no mitoses (n=4). Seven cases demonstrated areas of necrosis. Based on a combination of increased cellularity, mitotic activity, necrosis, nuclear pleomorphism, and infiltrativeness, 4 prostatic SFTs were malignant, 4 were benign, and 2 were borderline. Of the 3 non-prostatic SFTs, 1 was malignant and 2 were borderline. All tumors but 1 were immunoreactive for CD34 (n=12). Material for additional immunohistochemistry was available for the majority of cases with positive stains for Bcl-2 (11/11), CD99 (7/10), beta-catenin (5/10), and c-kit (0/11). Three SFTs demonstrated >or=10% p53 immunoreactivity including 1 tumor with 50% positivity; and 3 cases had Ki-67 rates of >or=20%. Although all SFTs were initially clinically considered to be of prostatic origin, some of the cases arose in the pelvis with secondary involvement of the prostate. Approximately 50% of prostatic SFTs were malignant. Even in the prostatic and nonprostatic SFTs with no overt malignant features, sometimes it was necessary to remove the prostate and in some instances the adjacent organs because of the large size of the tumors. SFTs must be differentiated from other spindle cell neoplasms of the prostate especially from gastrointestinal stromal tumors that may arise from the rectal wall with invasion of the prostate or from the region between the rectum and the prostate.

A solitary fibrous tumor in the broad ligament of the uterus.

Solitary fibrous tumor (SFT) is a rare mesenchymal tumor that occurs preferentially in the pleura. Although it has been described at some extrathoracic sites, its occurrence in the female genital tract is extremely rare. We are the first to report on an unusual case of a large (14cm in the largest diameter) SFT localized in the broad ligament of the uterus in a 50-year-old woman. The patient underwent surgical tumor extirpation and has remained well without any sign of local tumor recurrence after 6 years of follow-up. We discuss the clinical aspects, the gross macroscopic appearance, the histologic findings, and the differential diagnosis, and provide a review of the literature.

Solitary fibrous tumor of the pancreas: a case report.

Solitary fibrous tumor (SFT) is an unusual mesenchymal neoplasm that most often arises in the pleura; however, it has recently been described in a number of extrapleural sites. This report describes an extremely rare case of a benign SFT arising in the pancreas. A 41-year-old woman presented in the clinic with right upper abdominal pain. Subsequent ultrasonographic studies revealed a 1.5x1.5x1.4 cm hypoechoic mass within the pancreatic body, which was later confirmed on both helical computerized tomography and magnetic resonance imaging studies. An endocrine tumor was clinically suspected. Laparoscopic enucleation of the mass was performed. Microscopically, the tumor was composed of bland uniform spindle cells arranged between collagen bundles. On immunohistochemical studies, these spindle cells were positive for CD34 and bcl-2 but negative for cytokeratin (AE1+AE3 and Cam5.2), smooth muscle actin, desmin, S-100, and c-kit. Based on the light microscopic morphology and immunohistochemical staining profile, the diagnosis of SFT was rendered.

Comparison of sporadic sclerotic fibroma and solitary fibrous tumor in the oral cavity.

Sporadic sclerotic fibroma (SF) and solitary fibrous tumor (SFT) arising in the oral cavity are very rare. In this report, we describe two cases of oral pathology, one involving SF and the other involving SFT. Both cases presented with well- circumscribed, firm nodules with similar gross findings. However, the histologic findings of the SF and SFT showed rather distinct features. The SF was composed of hyalinized sclerotic collagen bundles arranged in a whorled pattern, whereas the SFT was formed by spindles cells arranged in hypo- and hypercellular areas. The immunohistochemical findings were similar in both cases; there was positivity for vimentin, CD34, and CD99, but bcl-2 positivity was only seen in the SFT. Although their histopathologies are similar, SF and SFT should be considered in the differential diagnosis of soft tissue tumors in the oral cavity.

Solitary fibrous tumor of the lung: a case report with a study of the aspiration biopsy, histopathology, immunohistochemistry, and autopsy findings.

Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm of ubiquitous location. In addition to its classic presentation as a pleural-based mass, it can be encountered in a variety of other sites. A pleural-based lung lesion can be easily accessed by radiologic guidance for cytologic study. Several reports have described the cytologic findings of SFT at various locations, including the lung. However, diagnostic difficulties can occur due to unusual clinical, radiologic, atypical cytomorphologic, and histologic features. We describe a case of intrapulmonary SFT in which a false-positive malignant diagnosis was rendered on fine-needle aspiration biopsy and concurrent surgical core biopsy prior to radiofrequency ablation. The patient died of procedural complications, and an autopsy was performed. Retrospective study of the case, especially correlation of cytologic, histologic, autopsy findings, and immunohistochemistry results were helpful in correctly diagnosing the case as SFT. We are reporting this case with emphasis on avoiding diagnostic pitfalls by being familiar with the accepted cytohistologic features and appropriate immunohistochemical results.

Solitary fibrous tumor of the liver.

BACKGROUND: Solitary fibrous tumor of the liver is a rare neoplasm. So far, 23 cases have been described in the English literature. We reported an additional case. METHODS: A 46-year-old woman presented with abdominal mass for 2 weeks. Both abdominal sonography and CT scan showed a solid mass occupying the right lobe of the liver. Right lobectomy was performed and the tumor was resected. RESULTS: Pathological examination showed spindle cell and fibroblast-like cells within the collagenous troma. On immunohistochemical staining, these spindle tumor cells showed diffusely CD34 positive reactivity. The post-operative course was uneventful. The patient recovered smoothly, and was alive half a year without evidence of disease recurrence. CONCLUSIONS: The proper diagnosis was depended on CD34 immunohistochemical study. The number of solitary fibrous tumor of the liver reported to date is too limited to confirm the definite prognosis of the tumor.

[Solitary orbital fibrous tumor in a 12-year-old child].

Solitary orbital fibrous tumor was diagnosed in a 12-year old boy admitted to hospital for right-sided exophthalmos. MRI revealed orbital mass and surgical resection was performed. Histologically the tumor was composed of round or spindle cells with a lot of multinucleate giant cells and pseudovascular spaces. The neoplasm was regarded as a mixoid type of a solitary giant cell-rich fibrous tumor. Immunohistochemical analysis revealed coexpression of CD34, CD99, bcl-2, and CD99 (mic-2). The most important clinical, morphological, and immunohistochemical manifestations are presented in the paper. Major criteria for the differential diagnosis of solitary orbital fibrous tumor and the similar soft tissue tumors are discussed.

Superficial CD34-positive fibroblastic tumor: Cytologic features, tissue correlation, ancillary studies, and differential diagnosis of a recently described soft tissue neoplasm.

Superficial CD34-positive fibroblastic tumor is a low-grade mesenchymal neoplasm of superficial soft tissues characterized by fascicles of spindle to epithelioid cells displaying nuclear pleomorphism and strong diffuse CD34 immunoreactivity. The intraoperative imprint cytology preparations (ICP) of a superficial CD34-positive fibroblastic tumor from a 50-year-old female are described. To the best of our knowledge, there is no report of the cytologic findings of superficial CD34-positive fibroblastic tumor in the English medical literature. The ICP, differential diagnosis, tissue correlation, and ancillary studies of this fascinating entity are discussed. Diagn. Cytopathol. 2016;44:926-930. © 2016 Wiley Periodicals, Inc.

Ultrastructural spectrum of solitary fibrous tumor: a unique perivascular tumor with alternative lines of differentiation.

Eight tumors diagnosed as solitary fibrous tumor (SFT) of the oral cavity were studied. Histologic spectrum was entirely comparable with the extrapleural SFT of other sites. One tumor had glomus tumor-like foci. Immunohistochemical results confirmed most of the previous observations, indicating characteristic expression of vimentin, CD34, bcl-2, and CD99. Factor XIIIa and alpha-smooth muscle actin were less commonly reactive and a very few cells were faintly positive for factor VIII-related antigen and Ulex europaeus agglutinin 1. All were essentially negative for S-100 protein, desmin, CD31, and CD68. In stark contrast to the conclusive immunoprofile, ultrastructural investigation of six tumors demonstrated considerable cellular heterogeneity. Other than fibroblasts, perivascular undifferentiated cells and pericytes predominated, but endothelial cells were regularly present. There was a distinctive proliferation of pericytic cells in four tumors, one of which had glomoid foci of myopericytes. The extreme increase in number of Weibel-Palade bodies occurred in voluminous capillary endothelium. Occasional single and clustered cells with consistent features of endothelium showed intracytoplasmic lumen formation. Such composite cells constituted an integral segment of richly vascularized SFT. Myofibroblastic form smooth muscle differentiation was present in only a minority of cells. From phenotypic analysis by electron microscopy, SFT may originate from a unique, perivascular multipotent mesenchyme sharing with its lineage with pericytes, fibroblasts, and infrequently, endothelium. Consequently, morphological features of SFT may become diversely varied by whether predominantly constituent cells are undifferentiated, pericytic or fibroblastic in nature.

Microvessel density and HIF-1alpha expression correlate with malignant potential in fibrohistiocytic tumors.

Angiogenesis is a central process in the growth of solid tumors. Hypoxia-inducible factor-1alpha (HIF-1alpha) is an oxygen-dependent transcriptional activator, which plays a crucial role in tumor angiogenesis. However, involvement of HIF-1alpha has never been studied in so-called fibrohistiocytic tumors, such as dermatofibroma (DF), dermatofibrosarcoma protuberans (DFSP) and malignant fibrous histiocytoma (MFH). We analyzed the extents of angiogenesis in relation to the expression levels of HIF-1alpha in 26 DF, 13 DFSP and 23 MFH cases. MFH showed significantly higher microvessel density (MVD) compared with DF and DFSP. Immunohistochemically, HIF-1alpha-positive cases constituted 31%, 15% and 98% of DF, DFSP and MFH, respectively, indicating significantly higher HIF-1alpha expression in MFH compared with DF and DFSP. Furthermore, MFH cases expressing high levels of HIF-1alpha showed significantly higher MVD than those with low levels of HIF-1alpha. Thus, higher levels of angiogenesis and HIF-1alpha expression are both closely associated with the malignant potential in so-called fibrohistiocytic tumors, and HIF-1alpha is possibly involved in angiogenesis in MFH.