Clear-cell variant of superficial cutaneous leiomyosarcoma associated with RB1 mutation: Clinical, dermoscopic, and histopathological characteristics.

Leiomyosarcoma is a relatively rare soft tissue tumor whose clear-cell variant has only been reported in leiomyosarcomas of the uterus. We report here for the first time a primary cutaneous clear-cell leiomyosarcoma in the trunk skin of a 49-year-old man, characterized by a very indolent clinical and dermoscopic presentation, mimicking a dermatofibroma. Genetic analysis of the otherwise healthy patient revealed a germline mutation in the retinoblastoma 1 gene (RB1); the same mutation was found in his son, who had previously developed retinoblastoma. Moreover, the mother of the patient had died of uterine leiomyosarcoma with clear-cell changes. Mutations in the RB1 gene occur commonly in human neoplasms. In this patient, we were able to link his clear-cell variant of cutaneous leiomyosarcoma with the loss of retinoblastoma protein expression, as revealed by immunohistochemical staining analysis.

Primary vaginal leiomyosarcoma: A case report with complete morphological, immunohistochemical and ultrastructural study.

OBJECTIVE: Primary vaginal leiomyosarcomas (LMS) are rare, easily recurrent tumours with an unknown etiology; the prognosis is poor and there is no consensus guideline on their management. CASE REPORT: A nodular, 25 × 23 x 28 mm-mass, infiltrating the urethra, was found in a 58-year-old woman. A biopsy showed a LMS of the vagina that was positive for vimentin, alpha-smooth muscle actin, caldesmon, desmin, p16 and p53. An anterior pelvic exenteration was performed. The sample was fixed and prepared for light microscopy, transmission and scanning electron microscopy, confirming the diagnosis of LMS. CONCLUSIONS: Best outcomes occur when the tumour is small, localized, and can be removed surgically with wide, clear margins, as in this case. As there are different kinds of malignant mesenchymal tumours, biopsy followed by immunohistochemistry and electron microscopy still represents a good diagnostic choice and surgical resection is generally the gold standard in these cases.

Molecular assembly, secretion, and matrix deposition of type VI collagen.

Monoclonal antibodies reactive with the tissue form of type VI collagen were used to isolate the type VI collagen polypeptides from cultured fibroblasts and muscle cells. Two [35S]methionine-labeled polypeptides of 260 and 140 kD were found intracellularly, in the medium, and in the extracellular matrix of metabolically labeled cells. These polypeptides were disulfide cross-linked into very large complexes. The 260- and 140-kD polypeptides were intimately associated and could not be separated from each other by reduction without denaturation. In the absence of ascorbic acid, both polypeptides accumulated inside the cell, and their amounts in the medium and in the matrix were decreased. These results suggest that both the 260- and the 140-kD polypeptides are integral parts of the type VI collagen molecule. Examination of type VI collagen isolated from the intracellular pool by electron microscopy after rotary shadowing revealed structures corresponding to different stages of assembly of type VI collagen. Based on these images, a sequence for the intracellular assembly of type VI collagen could be discerned. Type VI collagen monomers are approximately 125 nm long and are composed of two globules separated by a thin strand. The monomers assemble into dimers and tetramers by lateral association. Only tetramers were present in culture media, whereas both tetramers and multimers were found in extracellular matrix extracts. The multimers appeared to have assembled from tetramers by end-to-end association into filaments that had prominent knobs and a periodicity of approximately 110 nm. These results show that, unlike other collagens, type VI collagen is assembled into tetramers before it is secreted from the cells, and they also suggest an extracellular aggregation mechanism that appears to be unique to this collagen.

Primary hepatic myxoid leiomyosarcoma: a case report and review of the literature.

Sarcomas of the adult liver are unusual neoplasms, and can sometimes pose a difficult differential diagnosis. The authors report a myxoid spindle cell tumor arising in the liver of a 26-year-old woman. Histopathologic, immunohistochemical, and ultrastructural analysis demonstrated features of smooth muscle differentiation. Neoplastic nuclei were positive for estrogen receptor-beta and androgen receptor, but not estrogen receptor-alpha or progesterone receptor. Based on the large size of the tumor and the presence of conspicuous mitotic activity, the diagnosis of myxoid leiomyosarcoma was made. This case represents the third documented example of this tumor in the liver. The differential diagnosis in relation to this particular site of origin is discussed.

Polypoid uterine leiomyosarcomas in a sheep.

Leiomyosarcoma was diagnosed in the uterus surgically removed from a 3-year-old pet Suffolk ewe with a history of bleeding from the vulva, spontaneous lactation, and nursing behavior. The uterus contained multiple well-circumscribed, soft, intraluminal polypoid masses of variable sizes (0.5-4 cm). The masses were red, with white, smooth, and glistening cut surfaces. Histologically they comprised variably dense sheets of moderately pleomorphic, plump spindle cells embedded in richly vascularized stroma. The mitotic index was usually low (0-1/high-power field), but in some polyps there were up to 10 mitoses/high-power field. Neoplastic cells stained positive for alpha smooth muscle actin (alpha-SMA) by immunohistochemistry. Ultrastructural features of neoplastic cells included the presence of basal lamina, scant microfilaments, contracted nuclei with blunt ends, and flat intercellular junctions. Uterine leiomyosarcoma was diagnosed based on cellular morphology and atypia and positive immunohistochemistry for alpha-SMA.

Fine-needle aspiration of soft tissue leiomyosarcoma: an analysis of the most common cytologic findings and the value of ancillary techniques.

This study aims to determine the diagnostic accuracy of fine-needle aspiration cytology (FNAC) of primary leiomyosarcoma (LMS) of soft tissue and to review diagnostic criteria and adjunctive methods, which can contribute to a confident diagnosis. We evaluated the preoperative FNAC in 89 patients with primary LMS for the following: cytomorphology and correspondence of FNA to histological features of excised tumors and clinical data. In addition, the utility of adjunctive techniques was analyzed and other spindle-cell lesions in the differential diagnoses were discussed. An unequivocal, malignant diagnosis was rendered by FNAC in 78 cases; 74 tumors were diagnosed as sarcoma, of which 31 as LMS or suspicion of LMS. In addition, three smears were labeled as malignant tumor, one as carcinoma metastasis, and three as neurilemmoma. Seven aspirates were inconclusive and one insufficient. On reevaluation, the diagnostic smears in most cases contained tumor cell fascicles with an admixture of dispersed cells or stripped nuclei. The most common cells were spindle cells with elongated, blunt-ended, segmented or fusiform nuclei, and round/polygonal cells, often with rounded or indented nuclei. In addition, 51 cases showed pleomorphic, often multinucleated cells. Osteoclasts, intranuclear vacuoles, and mitoses occurred in 14, 47, and 27 cases, respectively. Thus, most high-grade LMSs have cytologic features that allow diagnosis of sarcoma. Ancillary studies can confirm the diagnosis of LMS and help in the correct interpretation of predominant spindle-cell or epitheloid-cell smears resembling neurilemoma or carcinoma, respectively.

Pulmonary metastatic leiomyosarcoma coexisting with pulmonary chondroma in Carney's triad.

The diagnosis of Carney's triad requires the coexistence of at least two of three rare disorders, including gastric epithelioid leiomyosarcoma, pulmonary chondroma, and functioning extra-adrenal paraganglioma. Seventeen cases have been reported so far, occurring predominantly in young female patients. We report herein the 18th case of this entity and the first case, to our knowledge, where pulmonary metastases from a gastric leiomyosarcoma coexisted in a patient with benign pulmonary chondromas.

Epithelioid leiomyosarcoma of the stomach. A case study of the intermediate filaments.

The intermediate filament typing of skeletal and smooth muscle tumors has shown that these neoplasms are characterized by the combined expression of desmin and vimentin intermediate filaments. A case of epithelioid leiomyosarcoma of the stomach was studied by conventional light microscopy and by indirect immunofluorescence using tissue-specific antibodies against intermediate filaments. The tumor cells labeled strongly with vimentin antibodies and were negative for desmin and prekeratin. This peculiar staining pattern may be the result of poor differentiation of the tumor cells with resultant loss of expression of desmin, or may be due to origin from a distinctive smooth muscle cell characterized by the exclusive expression of vimentin intermediate filaments.

Sarcomas with combined features of liposarcoma and leiomyosarcoma. Study of two cases of an unusual soft-tissue tumor showing dual lineage differentiation.

Two cases are described of a soft-tissue sarcoma characterized histologically by the intimate admixture of areas displaying the features of liposarcoma and leiomyosarcoma. Both cases occurred in men, 70 and 77 years of age. The lesions were located in the left scrotum and abdominal cavity, respectively. Histologically, the lipomatous component in both cases consisted predominantly of well-differentiated liposarcoma with myxoid areas. The smooth-muscle component was characterized by intersecting fascicles of spindle cells displaying nuclear atypicality and scattered mitotic figures; the spindle cells in these areas were strongly immunoreactive with actin and desmin antibodies. The above tumors must be distinguished from angiomyolipoma, spindle-cell lipoma, myolipoma of soft tissue, and more importantly, from "dedifferentiated" liposarcoma. The development of dual lineage differentiation within adipose tissue tumors as exemplified by these two cases may be more prevalent than has been generally recognized, and may require the application of immunohistochemical markers for specific identification of the spindle-cell component.

Retroperitoneal leiomyosarcoma. A clinicopathologic analysis of 36 cases.

Thirty-six cases of retroperitoneal leiomyosarcoma form the basis for this retrospective clinicopathologic study. This group comprised 24 females (67%) and 12 males (33%), whose ages ranged from 12 to 94 years (median, 60 years.). The clinical presentation, invariably nonspecific, consisted of pain or weight loss, typically associated with a palpable abdominal mass. Of the 30 patients with follow-up data, 23 (77%) died of retroperitoneal leiomyosarcoma. Grossly, the bulky often multinodular tumors, which ranged from 7.5 to 35 cm in maximal dimension (median, 12.8 cm), varied from firm to soft. In addition to the classical microscopic picture of leiomyosarcoma as manifested by interlacing fascicles of slender eosinophilic cells, other less frequently encountered, morphologic variations of malignant smooth-muscle tumors were also observed. Although absolute minimal criteria for a malignant tumor diagnosis could not be established, the findings suggest that a retroperitoneal smooth-muscle tumor that measures at least 7.5 cm in greatest dimension and that has as few as 1 mitosis/10 HPF is capable of metastasis.

Leiomyosarcoma of the broad ligament. A case report and literature review with follow-up.

A case of leiomyosarcoma arising in a preexisting leiomyoma of the broad ligament is presented with ultrastructural and Feulgen microspectrophotometric confirmation. This is the fourth reported case of leiomyosarcoma of the broad ligament and the second reported case to show evidence of a preexisting leiomyoma. Three of these patients died after intervals of 1, 7, and 19 months; one is alive and well with no evidence of disease after 12 years. The definitive evidence of malignant transformation of a leiomyoma has particular relevance to the controversy regarding the relationship of uterine leiomyosarcomas and leiomyomas.

Epithelioid leiomyosarcoma of the skin and subcutaneous tissue. Clinicopathologic, immunohistochemical, and ultrastructural study of five cases.

This report describes five cases of an unusual variant of malignant smooth-muscle neoplasm involving the skin and subcutaneous tissue characterized by a proliferation of predominantly round to oval epithelioid cells with abundant eosinophilic cytoplasm. Of the five patients, four were men, one a woman; ages ranged from 69 to 85 years (mean, 76.4). The size of the lesions varied from 1.2 to 2.5 cm; two were located in the scalp, two in the face, and one in the back of the neck. Immunohistochemical evaluation of the tumor cells showed immunoreactivity for actin and vimentin in all cases and negative labeling for desmin, S-100 protein, keratin, epithelial membrane antigen, HMB-45, factor VIII, and alpha-1-antichymotrypsin. Ultrastructural examination showed features of smooth muscle differentiation, that is, focal plasmalemmal densities, basement membrane material, and cytoplasmic filaments with focal condensations. All patients were treated by surgical excision and two also with post-operative radiotherapy. Two cases recurred after 1 year, requiring wide excision. A second recurrence from one of these cases showed the emergence of a highly anaplastic, pleomorphic spindle cell sarcoma; the patient died of unrelated causes, with evidence of persistent disease, after 2 years. In the remainder of cases, the patients were alive and well with no evidence of recurrence or metastasis from 2 to 6 years. Because of the unusual morphologic features of this variant of smooth-muscle tumor it may be confused with a variety of primary and metastatic neoplasms of the skin, including malignant melanoma, epithelioid sarcoma, and metastatic carcinoma. Epithelioid leiomyosarcoma should be recognized as a distinct morphologic variant of primary cutaneous smooth muscle neoplasm and should be considered in the differential diagnosis of epithelioid neoplasms in dermal and superficial soft tissue locations.

Leiomyoblastomas and their relationship to other smooth-muscle tumors of the gastrointestinal tract. An electron-microscopic study.

Twelve cases of gastrointestinal leiomyoblastoma were studied by electron microscopy, and the findings were compared with those in 12 cases of leiomyoma and nine cases of leiomyosarcoma of the gastrointestinal tract. All of the "classic" ultrastructural features of smooth-muscle tumors, including subplasmalemmal dense patches, pinocytotic vesicles, cytoplasmic microfilaments and dense bodies, and focal basement membrane formation, were present in the leiomyoblastomas ; however, extensive sampling was commonly necessary to demonstrate such findings. In contrast, these features were more prominent in leiomyomas and leiomyosarcomas.

Leiomyosarcoma of male breast originating in the nipple.

A case of leiomyosarcoma of the breast in a 53-year-old man originating in the erectile musculature of the nipple is presented. The tumor assumed roughly the conical configuration of the nipple musculature and was limited to the mammary gland. Ultrastructural study of the tumor revealed neoplastic smooth muscle cells with typical myofilaments.

Primary leiomyosarcoma of bone: a clinicopathologic, immunohistochemical, and ultrastructural study of 33 patients and a literature review.

Leiomyosarcoma of bone is a rare tumor in an unusual location. Previous analysis of this entity mostly involved small numbers of cases with limited follow-up. Thirty-three patients with leiomyosarcoma of bone between 1977 and 1996 were studied, and the histologic appearance and grade were correlated with subsequent treatment and clinical behavior. To be included in this study the tumor had to be intraosseous, with other primary sites of origin clinically excluded. Also, most of the sarcomatous tissue (> or =70%) had to be of intramedullary location with only limited extraosseous extension. The patient's age at diagnosis ranged from 13 to 77 years (average 44.4). The gender distribution was equal. The long bones were preferentially affected (64%), with the lower extremity, around the knee joint, predominantly involved. Five patients (15%) developed postradiation leiomyosarcomas. The histologic analysis showed that the osseous leiomyosarcomas are most commonly of the classic type, followed by the epithelioid, myxoid, and pleomorphic variants. Immunoreactivity for smooth muscle markers (smooth muscle actin, common muscle actin, desmin) was positive in all tumors, and ultrastructural confirmation was obtained in 21% of cases. All sarcomas were histologically graded, which accurately reflected the subsequent prognosis. Seventy-five percent of the lesions were high-grade and the rest low-grade. The histologic grade of the tumors correlated with both the recurrence as well as the metastatic rates and together with the clinicopathologic stage of disease represented the cornerstone on which prudent therapy should be based.

Uterine leiomyosarcomas and benign smooth muscle tumors: usefulness of nuclear DNA patterns studied by flow cytometry.

Flow cytometry was used to determine the DNA ploidy pattern of paraffin-embedded archival tissue specimens from 90 surgically resected uterine smooth muscle tumors (49 leiomyosarcomas and 41 leiomyomas). The technique of Hedley was used for preparation of paraffin-embedded tissue into single dissociated nuclei, and the method of Vindeløv was used for staining with propidium iodide. Among the 41 leiomyomas, most tumors (88%) had a DNA diploid pattern; the exceptions were two DNA tetraploid/polyploid and three DNA aneuploid samples. The DNA histograms of the 49 leiomyosarcomas (including 6 epithelioid leiomyosarcomas) were classified as follows: 9 cases (18%) exhibited a DNA diploid pattern, 29 cases (59%) had a DNA tetraploid/polyploid pattern, and 11 cases (23%) had DNA aneuploid peaks. Although DNA ploidy pattern cannot be used diagnostically to distinguish malignant from benign uterine smooth muscle tumors, the nuclear DNA ploidy pattern is an easily measured, objective determination that may have important prognostic significance for patients with uterine leiomyosarcomas.

Primary leiomyosarcoma of bone.

A primary tumor of bone, the light microscopic features of which were suggestive of malignant fibrous histiocytoma, proved to be a primary leiomyosarcoma upon electron microscopic examination. Ultrastructurally the tumor cells were smooth muscle cells having all the characteristic features, such as cytoplasmic filaments, cytoplasmic and sarcolemmal dense bodies, and pinocytotic vesicles, with a basal lamina surrounding the cells. This example emphasizes the importance of electron microscopy in diagnostic pathology. This is the second ultrastructural report of a primary leiomyosarcoma of bone.

Subcutaneous leiomyosarcoma with lymphomatous elements: histogenetic implications of an unusual sarcoma.

A 49-year-old woman had an unusual sarcoma that recurred three times in four years. The tumor manifested initially as a subcutaneous abdominal wall nodule composed of lymphohistiocytic malignant lymphoma and spindle cell sarcoma with epithelioid and clear cell elements. The neoplasm recurred first as a spindle cell sarcoma in the lumbar area, second as a malignant lymphoma in the subcutaneous tissue of the right shoulder, and third as a spindle cell sarcoma with lymphohistiocytic areas in the abdominal wall. Ultrastructural studies of this last tumor nodule demonstrated the unequivocal smooth muscle features of the spindle cells. Histogenetic implications of this neoplasm are discussed. It is proposed that the tumor represents an unusual variant of malignant mesenchymoma of soft tissues.

An unusual multifocal leiomyosarcoma of the stomach: a light and electron microscopic study.

A multifocal leiomyosarcoma of the stomach originating from the muscularis mucosae with lymph node and distant metastases is described in a 66 year old man. The electron microscopic features of a representative tumor mass and a metastasis confirmed the smooth muscle histogenesis. The light microscopic appearance consistently suggested malignant fibrous histocytoma. The pathological features of gasttric leiomyosarcomas are reviewed with special emphasis on the problem of practical diagnosis. This case also indicates that not all sarcomas with storiform features are necessarily histiocytic in origin.

Primary omental leiomyosarcoma masquerading as hemorrhagic ascites.

An 85-year-old man with unexplained hemorrhagic pseudoascites of four years' duration was discovered to have a primary omental leiomyosarcoma. Neoplasms arising in the greater omentum are rare. To date, only three primary omental leiomyosarcomas have been described. Clinical and pathologic findings of this case are presented and the topic of primary omental neoplasms is reviewed.