Absence of expression of SMARCB1/INI1 in malignant rhabdoid tumors of the central nervous system, kidneys and soft tissue: an immunohistochemical study with implications for diagnosis.

Malignant rhabdoid tumors are high-grade neoplasms of the central nervous system (CNS), kidneys and soft tissue that usually occur in children. The histologic diagnosis of malignant rhabdoid tumor depends on identification of characteristic rhabdoid cells-large cells with eccentrically located nuclei and abundant, eosinophilic cytoplasm-and immunohistochemistry with antibodies to vimentin, keratin and epithelial membrane antigen. In most malignant rhabdoid tumors, the SMARCB1/INI1 gene, located in chromosome band 22q11.2, is inactivated by deletions and/or mutations, so genetic diagnosis is often possible. However, tissue may not be available for genetic analysis or studies not confirmatory. We assessed SMARCB1/INI1 expression in 17 rhabdoid tumors and 57 other tumors of the CNS, kidney or soft tissue using immunohistochemistry. In total, 12 brain, three renal and two soft tissue rhabdoid tumors were examined along with four glioblastomas, four pilocytic astrocytomas, four oligodendrogliomas, two ependymomas, two choroid plexus papillomas, five pituitary adenomas, four germinomas, four renal carcinomas with Xp11.2 translocations, two clear cell sarcomas, two Wilms' tumors, one renal medullary carcinoma, two desmoplastic small round cell tumors, two alveolar rhabdomyosarcomas, two embryonal rhabdomyosarcomas, one low-grade chondrosarcoma, two extraskeletal myxoid chondrosarcomas, one mesenchymal chondrosarcoma, four malignant peripheral nerve sheath tumors, five metastatic carcinomas and four epithelioid sarcomas, two primary and two metastatic. The neoplastic cells of all rhabdoid tumors, the four epithelioid sarcomas and the renal medullary carcinoma did not express SMARCB1/INI1 by immunohistochemistry; neoplastic cells of all other tumors expressed SMARCB1/INI1. Immunohistochemistry to assess expression of SMARCB1/INI1 may be useful in the diagnosis of rhabdoid tumors of the CNS, kidneys and soft tissue.     

Expression of dentin matrix protein 1 in tumors causing oncogenic osteomalacia.

Oncogenic osteomalacia, which is characterized by renal phosphate wasting, low serum 1, 25-dihydroxyvitamin D, and osteomalacia, is caused by mesenchymal neoplasms that are termed phosphaturic mesenchymal tumors (PMTs). As PMTs are usually small and lack specific histological features, the pathological identification of PMTs is difficult. Dentin matrix protein 1 (DMP1) is an acidic phosphoprotein expressed in mineralized tissues including bone, tooth, and hypertrophic cartilage. Increased expression of DMP1 gene in PMTs has been reported by using differential cDNA screening. In the present study, DMP1 expression in PMTs and other soft tissue tumors was analyzed immunohistochemically to verify its utility in the differential diagnosis of PMTs. Anti-DMP1 polyclonal antibody was raised against the C-terminal sequence of DMP1. Three cases with PMTs and 11 other soft tissue tumors (two malignant hemangiopericytomas, three solitary fibrous tumors, three synovial sarcomas, and three malignant peripheral nerve sheath tumors) were analyzed for DMP1 expression. DMP1 expression was observed in all of the three cases with PMTs, but never found in other soft tissue tumors examined. DMP1 was detected in the extracellular matrix with myxomatous features or around capillary vessels, and in dystrophic calcified sites. Paranuclear DMP1 staining in the tumor cells was also observed. These findings indicate that DMP1 immunohistochemistry is a useful tool for identifying PMTs.     

Malignant soft tissue tumors (malignant fibrous histiocytoma, pleomorphic liposarcoma, and pleomorphic rhabdomyosarcoma): an electron microscopic study.

A comparative ultrastructural analysis of malignant soft tissue tumors (malignant fibrous histiocytoma, pleomorphic liposarcoma, and pleomorphic rhabdomyosarcoma) revealed similar ultrastructural features in this group of tumors. However, by electron microscopy these tumors can be differentiated on the basis of cytoplasmic and extracytoplasmic features (myosin filaments, lipid droplets, and perinuclear intermediate filaments, for example). This is even true of less well differentiated tumors and tumor cells. These findings support and amplify the concept of a common histogenesis for tumors of mesenchymal origin. Paradoxical features observed by light microscopy warrant further study by electron microscopy if the correct diagnosis is to be made in atypical cases, such as apparent malignant fibrous histiocytoma with cross striations.     

Fine‐needle aspiration cytology of epithelioid malignant peripheral nerve sheath tumor: A case report and review of the literature

The epithelioid variant of malignant peripheral nerve sheath tumor (eMPNST) is an extremely rare soft tissue neoplasm comprising less than 5% of all MPNSTs. It is distinguished cytomorphologically from a conventional MPNST by the presence of polymorphous round epithelioid cells arranged in loose clusters with or without spindled tumor cells. These features pose a diagnostic challenge because the differential diagnosis involves a variety of mesenchymal and non‐mesenchymal tumors including epithelioid sarcoma, sclerosing epithelioid fibrosarcoma, malignant rhabdoid tumor, chordoma, metastatic carcinomas, and melanoma. Thus, it may become imperative to perform immunochemical stains on cell blocks of FNA aspirates to arrive at definitive diagnosis. Reports describing the cytologic features of eMPNST are rare. Herein, we report a case of eMPNST with focus on cytomorphologic and cytoimmunochemical features and differential diagnosis. Diagn. Cytopathol. 2016;44:226–231. © 2015 Wiley Periodicals, Inc.     

Malignant fibrous histiocytoma with special reference to its differential diagnosis

The histological diagnosis of malignant fibrous histiocytoma (MFH) seems to have become recently fashionable among pathologists, although its histogenesis and diagnostic criteria are not entirely settled as yet. For practical purposes the differential diagnosis with other easily mistakable mesenchymal tumors should be strictly made with great caution, because of variable histological features of this tumor. The authors attempted to elucidate the differential points from other tumors in a review of 189 cases of malignant soft tissue tumors. Some cases of carcinoma mimicking MFH were also reviewed. No single criterion for making the histological diagnosis of MFH was obtained. Its histological features and differential points from pleomorphic rhabdomyosarcoma and fibrosarcoma were tabulated. The recognition of a true tumor osteoid was emphasized as a single differential point between osteosarcoma and MFH often with fibrous areas mimicking osteoid. Renal cell carcinoma metastasizing to bone, which was misinterpreted as MFH on biopsy tissue, was also described and its differential point was stated.     

Primary soft tissue tumors of the retroperitoneal space

Primary soft tissue tumors of the retroperitoneal space are seldom. In the last 40 years there are only some reports on larger tumor series. But their comparison is merely possible reservedly because in the past the classification of soft tissue tumors was repeatedly changed. Using the diagnostic criteria of the WHO we examined 96 primary tumors of the retroperitoneal soft tissue concerning the distribution of the histological types. 25 cases were classified as benign tumors. 44% of the lesions were benign schwannomas, in the frequency they were followed by leiomyomas (16%), fibromatoses (12%), lipomas (8%) and fibromas (8%). All fibromatoses were localized in the mesenteric radix. 71 tumors were considered to be malignant. The most frequent malignant growths were leiomyosarcomas (24%). Malignant fibrous histiocytomas and liposarcomas constituted 15.5% and 14% of the malignant tumors, resp. Rhabdomyosarcomas were relatively seldom and only of the embryonal type. They exclusively occurred in childhood. Fibrosarcomas were just found in 3% of cases and synovial sarcomas were completely lacking. 17% of all malignant tumors could not be classified with certainty. Whereas the diagnosis of benign soft tissue tumors is not too difficult as a rule the malignant lesions not seldom resist an exact classification. General problems in diagnosis are discussed, differential diagnostic criteria for a clear separation of different tumor entities are presented. Finally the importance of a histological grading of malignant retroperitoneal soft tissue tumors is emphasized.     

p63 immunohistochemical staining is limited in soft tissue tumors

p63 is a p53 homolog that is expressed in various normal epithelial tissues and epithelial malignancies. Its expression in mesenchymal lesions has not been examined in depth; therefore, we studied p63 expression by immunohistochemical analysis in 650 soft tissue tumors. We found that p63 expression is limited in soft tissue tumors. The majority of tumors studied were p63-, including all cases of angiosarcoma, lipomatous neoplasms, dermatofibrosarcoma protuberans, solitary fibrous tumor, schwannoma, neurofibroma, gastrointestinal stromal tumor, and leiomyosarcoma. Nuclear p63 reactivity was found in a subset of soft tissue myoepithelioma and myoepithelial carcinoma of soft tissue, cellular neurothekeoma, soft tissue perineurioma, Ewing sarcoma/peripheral neuroectodermal tumor, diffuse-type giant cell tumor, and giant cell tumor of soft parts. Infrequent, weak, or focal p63-staining patterns were observed in low-grade fibromyxoid sarcoma, malignant peripheral nerve sheath tumor, extraskeletal myxoid chondrosarcoma, myxofibrosarcoma, proximal-type epithelioid sarcoma, synovial sarcoma, embryonal rhabdomyosarcoma, desmoplastic small round cell tumor, atypical fibroxanthoma, and spindle cell melanoma. Absent p63 expression is typical for most soft tissue tumors, including most (but not all) that would be in the differential diagnosis of spindle cell squamous carcinoma.     

Glomus tumor

Glomus tumor is a benign mesenchymal neoplasm comprising less than 2% of soft tissue tumors. It is composed of cells resembling modified smooth muscle cells of the normal glomus body. The glomus body, a thermoregulator, is a specialized form of arteriovenous anastomosis localized in dermal and precoccygeal soft tissue. Although glomus tumors are rare neoplasms, clinical misdiagnosis of many of these lesions as hemangiomas or venous malformations makes an accurate assessment of their actual prevalence difficult. A malignant counterpart of this lesion exists but is extremely rare.     

Primary retroperitoneal synovial sarcoma: a case report

A case of a 36-yr-old woman with retroperitoneal synovial sarcoma is described. Her presenting symptom was epigastric pain that radiating to the back. On radiologic study, bulky retropancreatic soft tissue mass was detected which showed cystic and solid components. At operation, complete resection of the tumor was not possible because of the adhesion to the vena cava and the liver. During the follow-up, extensive tumor recurrence and liver metastasis were revealed. Primary retroperitoneal synovial sarcoma is a very rare malignant tumor with high mortality and recurrence rates. Retroperitoneal synovial sarcoma usually appears as a nonspecific soft tissue mass that do not have specific imaging features differentiating it from other mesenchymal tumors. However general radiologic findings and anatomic location of the tumor may help the diagnosis. In addition, synovial sarcoma should be included in the differential diagnosis of retroperitoneal soft tissue mass detected in young adults.     

A case of a pleomorphic hyalinizing angiectatic tumor of soft parts with intracytoplasmic hemosiderin pigment apparent upon fine‐needle aspiration cytology

Pleomorphic hyalinizing angiectatic tumors of soft parts are extremely rare low‐grade mesenchymal lesions that frequently occur subcutaneously, especially in the lower extremity. The tumor is histologically characterized by sheets of plump, spindled or rounded cells, and clusters of ectatic blood vessels. It also has a number of previously characterized cytological features such as pleomorphic cells, intranuclear pseudoinclusion, and intracytoplasmic hemosiderin pigments. However, intracytoplasmic hemosiderin has not been carefully evaluated in cytology specimens. Here, we report the case of a 56‐year‐old Japanese man with an encapsulated pleomorphic hyalinizing angiectatic tumor of soft parts that included fine and coarse hemosiderin‐laden tumor cells. The tumor was clinically followed up as a hematoma, but malignant tumors, including malignant melanoma, were suspected because aspiration cytology specimens contained pleomorphic cells with intracytoplasmic brown pigments. The tumor was closely associated with an intratumoral hematoma and a few microscopic satellite lesions. Pleomorphic hyalinizing angiectatic tumor of soft parts should be included in the differential cytological diagnosis of soft tissue tumors if the three cytological features described earlier are present. Enucleation therapy could facilitate local recurrence, as the tumor may have the potential to infiltrate surrounding soft tissue or form satellite lesions. Diagn. Cytopathol. 2015;43:407–411. © 2014 The Authors. Diagnostic Cytopathology Published by Wiley Periodicals, Inc.     

Fine-needle aspiration cytology and immunocytochemistry of soft-tissue tumors and osteo/chondrosarcomas of the head and neck

The purpose of the study was to present the clinical and cytological findings of 28 cases of malignant or borderline mesenchymal tumors of the head and neck, of which 22 originated from soft tissue and 6 were found in bone or cartilage. The basic procedures employed involved a cytologic review and subclassification of fine-needle aspiration (FNA) smears from the tumors, which were diagnosed as: pleomorphic sarcomas (5 poorly differentiated, 1 angiosarcoma, and 1 epithelioid sarcoma), spindle-cell sarcomas (2 leiomyosarcomas, 2 malignant mesenchymal tumors, and 1 malignant schwannoma), myxoid sarcomas (2 liposarcomas and 1 high-grade tumor), round-cell tumors (1 malignant histiocytic tumor and 1 chloroma), osteosarcomas (3), chondrosarcomas (3), and borderline tumors (2 pleomorphic lipoma, 1 myxolipoma, 1 cranial fasciitis, and 1 fibromatosis). Histological correlation and problems in subtyping on both cytologic and histological material are discussed. It is concluded that FNA cytology can be used with high accuracy to diagnose musculoskeletal tumors in rare sites such as the head and neck.     

Collagen-rich tumors of soft tissues: an overview

Although relatively common, soft tissue tumors frequently present diagnostic problems for practicing pathologists. Immunohistochemistry has facilitated the diagnosis of many mesenchymal tumors; however, there is considerable overlap in the staining profiles among cells demonstrating fibroblastic and myofibroblastic differentiation. It has been our experience that soft tissue tumors associated with abundant extracellular collagen deposition commonly cause problems in classification. One reason for this is that tumors displaying this morphology include representatives from different histogenetic families. Specifically, tumors exhibiting fibroblastic, myofibroblastic and even lipomatous differentiation may manifest as a densely collagenous mass. It is the purpose of this review to highlight these collagen-rich soft tissue tumors.     

Diagnosis of soft tissue tumors by fine-needle aspiration with combined cytopathology and ancillary techniques

The diagnosis of mesenchymal neoplasm by fine-needle aspiration biopsy (FNAB) has presented a diagnostic challenge. Most reports claim an accuracy approaching 95%, but while they distinguish benign and malignant lesions, the most problematic group, the intermediary malignant group, is omitted. The purpose of this study was to determine whether rapid cytologic diagnosis of soft-tissue tumors could guide surgeons in therapeutic decisions without the need for a tissue biopsy. Ninety-four FNA cytologic specimens were examined by the National Soft Tissue Consortium of Hungary and compared with the corresponding histology. Ordinary lipomas were excluded. Morphologic evaluation was supplemented by ancillary techniques such as fluorescence in situ hybridization (FISH), DNA cytometry, and immunocytochemistry. From a practical clinicopathological point of view, the cases were grouped in the following categories: 1) tumors with definitive diagnosis: a) high-grade malignant neoplasms (high-grade sarcomas, metastatic carcinomas, lymphoma), b) tumors with precise histogenetic origin by cytogenetics, c) benign tumors; 2) tumors of questionable nature. In the first group there were 74 tumors: 22 high-grade sarcomas, six metastatic carcinomas, one malignant lymphoma, 16 malignant tumors in which the precise histogenetic origin could be established by cytogenetic studies, and 29 benign soft-tissue tumors other than lipomas. In the second group there were 20 tumors comprising benign and malignant soft tissue tumors of low grade, wherein the precise nature of the neoplasm could not be established with confidence on cytologic study, even using ancillary techniques. FNAB of soft-tissue tumors combined with ancillary techniques should be considered a viable diagnostic technique for therapeutic protocols. Although the second group is fairly large, we have reliable, well-characterized categories which provide great freedom for preoperative and surgical treatment, thus providing the best chance for healing.     

Histological grading and MIB-1 labeling index of soft-tissue sarcomas

Soft-tissue sarcomas or malignant soft-tissue tumors are malignant tumors arising from soft tissues of mesenchymal origin. These soft-tissue tumors can develop from any site in the body, including the extremities, trunk, retroperitoneum, or the head/neck region. In Japan, soft-tissue sarcomas are rarely encountered, with an incidence of approximately 2 per 100 000 population. Diverse types (more than 30 types) of soft-tissue sarcomas are known. Pathological examination of biopsy or resected specimens is indispensable for a definitive diagnosis of soft-tissue sarcomas. Needless to say, early detection and treatment based on accurate diagnosis are the basic principles of the management of soft-tissue sarcomas. The purpose of the present paper was to address the histological grading of soft-tissue sarcomas (the most important histopathological prognostic factor for this type of sarcoma) based on the French Fédération Nationale des Centres de Lutte Contre Ie Cancer (FNCLCC) system, the histological grading of this type of sarcoma based on the MIB-1 labeling index (an immunohistochemical marker of cell proliferation; MIB-1 system), precautions that must be taken while evaluating the degree of malignancy and the relationship of the grade with other clinicopathological factors.     

Inflammatory myofibroblastic tumor of the pancreas with regional lymph node involvement

Inflammatory myofibroblastic tumors (IMT) can be found in virtually any location of the human body. Histologically a mesenchymal aspect predominates and makes these mostly benign tumors apt to be erroneously diagnosed as a soft tissue sarcoma. Cases showing infiltrative growth and local recurrence further complicate the assessment. Localization of an IMT in the pancreas is extremely rare. Clinical investigations regularly lead to the putative diagnosis of a malignant tumor and only subsequent histological examination can establish the correct tumor classification. We present the case of a 62-year-old woman with IMT of the pancreas. Evidence of lymph node involvement has not yet been reported in this setting.     

Sarcomatous Type of Malignant Mesothelioma

Thirteen malignant mesotheliomas of a sarcomatous type were studied by light microscopy and ten were studied by electron microscopy. The histologic patterns varied from tumor to tumor, often resembling other soft tissue sarcomas. Electron microscopic observation showed most of the tumors to be composed of primitive cells. Despite their mesenchymal character, many tumors contained foci of rudimentary epithelial differentiation. It is concluded that both histologic types of malignant mesothelioma, the epithelial as well as the sarcomatous, originate from the same precursor cell at various points of its differentiation and reflect the range of maturation from the mesenchymal reserve cell to the epithelial mesothelial cell.     

Sarcomatous Type of Malignant Mesothelioma

Thirteen malignant mesotheliomas of a sarcomatous type were studied by light microscopy and ten were studied by electron microscopy. The histologic patterns varied from tumor to tumor, often resembling other soft tissue sarcomas. Electron microscopic observation showed most of the tumors to be composed of primitive cells. Despite their mesenchymal character, many tumors contained foci of rudimentary epithelial differentiation. It is concluded that both histologic types of malignant mesothelioma, the epithelial as well as the sarcomatous, originate from the same precursor cell at various points of its differentiation and reflect the range of maturation from the mesenchymal reserve cell to the epithelial mesothelial cell.     

Undifferentiated and dedifferentiated soft tissue neoplasms: Immunohistochemical surrogates for differential diagnosis

Undifferentiated soft tissue sarcomas (USTS) are described in the current World Health Organization Classification of Soft Tissue and Bone Tumours as those showing no identifiable line of differentiation when analyzed by presently available technologies. This is a markedly heterogeneous group, and the diagnosis of USTS remains one of exclusion. USTS can be divided into four morphologic subgroups: pleomorphic, spindle cell, round cell and epithelioid undifferentiated sarcomas, with this combined group accounting for up to 20% of all soft tissue sarcomas. As molecular advances enable the stratification of emerging genetic subsets within USTS, particularly within undifferentiated round cell sarcomas, other groups, particularly the category of undifferentiated pleomorphic sarcomas (UPS), still remain difficult to substratify and represent heterogeneous collections of neoplasms often representing the common morphologic endpoints of a variety of malignant tumors of various (mesenchymal and non-mesenchymal) lineages. However, recent molecular developments have also enabled the identification and correct classification of many tumors from various lines of differentiation that would previously have been bracketed under ‘UPS’. This includes pleomorphic neoplasms and dedifferentiated neoplasms (the latter typically manifesting with an undifferentiated pleomorphic morphology) of mesenchymal (e.g. solitary fibrous tumor and gastrointestinal stromal tumor) and non-mesenchymal (e.g. melanoma and carcinoma) origin. The precise categorization of ‘pleomorphic’ or ‘undifferentiated’ neoplasms is critical for prognostication, as, for example, dedifferentiated liposarcoma typically behaves less aggressively than other pleomorphic sarcomas, and for management, including the potential for targeted therapies based on underlying recurrent molecular features. In this review we focus on undifferentiated and dedifferentiated pleomorphic and spindle cell neoplasms, summarizing their key genetic, morphologic and immunophenotypic features in the routine diagnostic setting, and the use of immunohistochemistry in their principal differential diagnosis, and highlight new developments and entities in the group of undifferentiated and dedifferentiated soft tissue sarcomas.     

Case Report: Microtubular Aggregates within the Rough Endoplasmic Reticulum of Embryonal Rhabdomyosarcoma Cells: A Case Report

This study presents a case of embryonal rhabdomyosarcoma (ERMS) of the forearm soft tissue in a 12-year-old female, in which microtubular aggregates in rough endoplasmic reticulum (rER) were noted ultrastructurally. Histologically, tumor cells consisted of typical rhabdomyoblastoid cells with abundant eosinophilic cytoplasm and relatively immature, small tumor cells. Ultrastructurally, two different types of tumor cells were also identified by light microscopy. More than half the tumor cells possessed the characteristic features of rhabdomyoblastic differentiation, such as abundant thick and thin filaments with Z-bands. The other tumor cells were less differentiated cells in which microtubular aggregates (MA) in rER were observed. MA in rER have been described in several nonepithelial tumors, including malignant melanoma, osteosarcoma, extraskeletal myxoid chondrosarcoma, and chordoma. ERMS is another example of mesenchymal tumor in which MA in rER are observed by electron microscopy. Considering the differential diagnosis among mesenchymal tumors, it is important to know that MA can be also observed in ERMS.