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.

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.

Primitive testicular leiomyosarcoma.

Primary testicular leiomyosarcoma is an uncommon tumor with only few cases described in literature. In young people this rare tumor seems to be related to radiotherapy and anabolic steroids abuse. In older people there are apparently no risk factors. We describe one further case in a 77-years old man with full histological and ultrastructural evaluation. A short term follow-up of one year signals no recurrence of the disease.

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.

Leiomyosarcoma of the larynx: critical analysis of the diagnostic role played by immunohistochemistry.

Laryngeal leiomyosarcoma (LMS) is definitely considered a rare occurrence: our exhaustive literature review disclosed to date only 45 cases (including the new case we have reported). The morphological diagnosis of laryngeal LMS may be problematic on conventional light microscopy especially in small laryngeal specimens. In the past, LMSs of the larynx were frequently confused with other spindle-cell malignant tumors. Nowadays, immunohistochemical investigations are considered necessary to distinguishing LMS from other spindle-cell tumors. On immunostaining, LMS is usually positive for muscle-specific actin and negative for cytokeratins and epithelial membrane antigen. In most cases, immunohistochemical study allows reliable diagnosis of LMS, but it can produce ambiguous or inconclusive results when the tumor cells lack specific immunohistochemical reactivity. In these controversial cases, LMS diagnosis has to be substantiated by electron microscopy. Distinguishing laryngeal LMS from other spindle-cell malignancies plays a role not only in academic interest. Confusion in the diagnosis of a spindle-cell laryngeal malignancy could result in inappropriate clinical management and inadequate treatment.

Histochemical and ultrastructural study of an elastofibroma dorsi coexisting with a high grade spindle cell sarcoma.

Elastofibroma dorsi is a pseudotumoral fibroproliferative lesion characterized by polymorphic fiber-like deposits of elastinophilic material. Several theories have been reported explaining the pathogenesis of elastofibroma. Recent cytogenetic studies have demonstrated chromosomal instability in elastofibromas, not normally observed in non-neoplastic tissues. These chromosomal defects are commonly observed in aggressive fibromatosis too. Such clinical observations suggest a multistage pathogenetic mechanism for the onset of elastofibroma. This study, using histochemical, immunohistochemical staining techniques, and ultrastructural examination, describes the detection of an otherwise typical elastofibroma contextual to a high grade sarcoma. Hence, the coexistence of elastofibroma and high-grade sarcoma may suggest a causal link between the two pathological entities. The results obtained suggest that the coexistence of the two pathological entities is conceivably coincidental.

Dumbbell-shaped leiomyosarcoma of the inferior vena cava with foci of rhabdoid changes and osteoclast-type giant cells.

An inferior vena cava (IVC) tumor was incidentally found in a 67-year-old Japanese man. The resected tumor was lobulated and multinodular, measuring 14.0 x 6.5 x 7.0 cm, showing a dumbbell-shaped appearance with a central constriction. The tumor showed both intra- and extra-luminal growth. The tumor was primarily composed of well-differentiated leiomyosarcoma. Spindle tumor cells in the well-differentiated area were positive for vimentin, muscle actin, alpha-smooth muscle actin, and desmin. Foci of rhabdoid cells and osteoclast-type multinucleated giant cells were also found. Rhabdoid cells ultrastructurally had paranuclear aggregates or whorls of intermediate filaments that were positive for vimentin, low molecular weight cytokeratin, and desmin. Osteoclast-type multinucleated giant cells were positive for only CD68 antigen, suggesting a reactive histiocytic lineage. To the best of our knowledge, this is the first case of IVC leiomyosarcoma accompanied by both rhabdoid tumor cells and osteoclast-type reactive multinucleated giant cells. These unusual features should be kept in mind in the diagnosis of dumbbell-shaped retroperitoneal tumors that involve the IVC.

Leiomyosarcoma arising from soft tissue tumor of the mediastinum.

The occurrence of a leiomyosarcoma (LMS) in soft tissue of the mediastinum is rare. We report a 60-year-old woman with an LMS in mediastinal soft tissue who died 8 months after surgical removal. Pathological, immunohistochemical, and electron microscopic features of this rare tumor are described.

Contribution of electron microscopy to understanding cellular differentiation in mesenchymal tumors of the gastrointestinal tract: a study of 82 tumors.

Eighty-two mesenchymal tumors of the gastrointestinal tract were examined by electron microscopy for the purposes of subtyping for diagnostic precision and of understanding cellular differentiation. Tumors were subclassified into leiomyoma/leiomyosarcoma, tumors of the interstitial cell of Cajal (equivalent to traditionally defined GISTs [Miettinen et al. Hum Pathol. 1999; 30:1213-1220; Mod Pathol. 2000; 13:1134-1142]), gastrointestinal autonomic nerve tumors (GANTs), and fibroblastic and myofibroblastic tumors, using criteria from the literature. Leiomyoma/leiomyosarcoma were diagnosed by myofilaments, attachment plaques, plasmalemmal caveolae, and lamina; GIST by processes or cell bodies full of intermediate filaments, solitary focal densities amid intermediate filaments, attachment plaques with incomplete lamina, scarce myofilaments, and smooth endoplasmic reticulum; GANTs by neuroendocrine granules, cell bodies/processes full of intermediate filaments (more rarely microtubules), and smooth endoplasmic reticulum; fibroblastic/myofibroblastic tumors by abundant rough endoplasmic reticulum, myofilaments, and fibronexuses. Seventy-three tumors (89%) were successfully subclassified, as 5 leiomyoma/leiomyosarcoma (6%), 36 GISTs (44%), 22 GANTs (27%), 10 fibroblastic and myofibroblastic tumors (12%). Results indicated overlap between poorly differentiated leiomyosarcoma and GIST, and between GIST and GANT. GANT is emphasized as a neuronal tumor identifiable by electron microscopy, and thereby distinguishable from GIST.

Leiomyosarcoma showing partial synthetic-phase differentiation.

An unusual leiomyosarcoma in the thigh of a 53-year-old woman is described. Tumor cells were spindled and positive for muscle immuno-markers. Some cells exhibited typical smooth-muscle ultrastructure--abundant myofilaments, focal densities, attachment plaques, plasmalemmal caveolae, and lamina. Others had fewer myofilaments and prominent rough endoplasmic reticulum. These features indicated a variable phenotype that included synthetic-phase (matrigenic) differentiation. Synthetic-phase cells were distinguished from myofibroblasts by typical smooth-muscle surface features in the absence of fibronexus junctions. In a subset of cells myofilaments were absent, but structures resembling solitary focal densities were identified. These are discussed as possible indicators of a primitive level of smooth-muscle differentiation.

Peritoneal washing cytology findings of disseminated myxoid leiomyosarcoma of uterus: report of a case with emphasis on possible differential diagnosis.

We report the cytology findings of a rare case of myxoid leiomyosarcoma of the uterus with intraabdominal dissemination. The cytology showed uniformly dispersed spindly to polygonal "epithelioid" tumor cells focally linked by background matrix. Spindly tumor cells attaching to and radiating from branching capillary structures were also present. Occasionally, scattered "signet-ring" cells were found, mimicking metastatic poorly differentiated adenocarcinoma. The background mucoid substance was more conspicuous in the cell block sections. Gross and histologic examination of the surgical specimen revealed a large uterine leiomyosarcoma with prominent myxoid change. Ultrastructural study showed that the "signet-ring" appearance was mainly due to degenerative cytoplasmic change with ballooning of mitochondria, dilatation of endoplasmic reticulum, and elevation of outer nuclear membrane. In contrast to other spindle cell malignancies such as sarcomatoid mesothelioma, sarcomatoid carcinoma, or malignant melanoma, true sarcoma cells in general carry a distinctive cytologic appearance in washing/effusion fluid. In a correct clinical setting, the peculiar association with mucoid matrix and absence of classic lipoblasts should also raise the suspicion of metastatic myxoid leiomyosarcoma.

Myofibrosarcoma of the upper jawbones: a clinicopathologic and ultrastructural study of two cases.

Two problematic spindle cell sarcomas involving upper jawbones in two adult male patients have been studied by histology, immunohistochemistry, and transmission electron microscopy, and respectively graded as low-grade malignancy and high-grade malignancy. While any single methodological study did not allow confident classification of them into one or other of the classical categories of spindle cell sarcomas (fibrosarcoma versus leiomyosarcoma), the overall contribution from all three methodologies ultimately allowed them to be categorized as sarcomas with myofibroblastic differentiation. Histologically, both tumors had morphological features of an amalgama between neoplastic fibroblasts and smooth muscle cells. Immunohistochemically, both tumors expressed reactivity only for muscle specific actin and alpha smooth muscle actin, in addition to vimentin. Ultrastructurally, both tumors, while showing fibroblast-like cytoplasmic features, had a spurious and imperfectly organized cell surface defying convincing classification into any of specific categories (i.e., both appeared in terms of ultrastructure as poorly differentiated sarcoma, the former with low level of smooth muscle differentiation and possibly the presence of some fibronexus component, the latter with no smooth muscle differentiation but with possible evidence of very rare fibronectin fibril). Therefore, on balance, the most tenable diagnosis seemed to us that of a myofibrosarcoma in both cases. This work is presented considering the fact that myofibrosarcoma currently represents a topical theme of debate, and that this is the first report in medical literature concerning with myofibrosarcomas of the head and neck area in adults.

Morphologic-cytogenetic analysis of dedifferentiated liposarcomas with an extensive misleading leiomyosarcomatous component.

This report describes two cases of recurrent retroperitoneal dedifferentiated liposarcoma characterized by an extensive leiomyomatous component that prevented the correct diagnosis before the last recurrence. Strong immunoreactivity with smooth muscle and desmin antibodies and ultrastructural features consistent with leiomyosarcoma were observed in the spindle-cell and/or myxoid-like components in all four recurrences in case 1, and in the spindle-cell component of the primary tumor and the first recurrence in case 2. In case 1, the correct diagnosis was suggested by the cytogenetic evidence of ring markers, a hallmark of well-differentiated/dedifferentiated liposarcoma. In case 2, tumor type was yielded mainly by the morphology of the second recurrence, which consisted entirely of a well-differentiated liposarcoma, a sclerosing inflammatory variant, as confirmed by the karyotype. Reevaluation of the first two surgical specimens of each case revealed small areas consistent with well-differentiated liposarcoma that had been previously overlooked. Despite the smooth-muscle antigen profile, both cases retained an mdm2+/p53+/cdk4+ immunophenotype consistent with the genotype.

[Malignant stromal tumor of the transverse colon. Case report]. / Tumor estromal maligno de colon transverso. Informe de un caso.

OBJECTIVE: Case report of a malignant stromal tumor of the transverse colon. BACKGROUND: Colon sarcomas are rare; the most frequent presentation is the leiomyosarcoma. Forty five cases of malignant stromal tumor have been reported in the international literature. The histogenesis of these mesenchymatous neoplasms is determined by ultrastructural analysis and immunohistochemical stains, nevertheless when special techniques are negative and there is uncertainty related to the cellular differentiation line (smooth muscle, neural or undifferentiated) it is preferable to call them stromal tumors of gastrointestinal tract. METHOD: A 46 year old patient with the diagnosis of malignant stromal tumor of transverse colon and the prescribed treatment was reported. RESULTS: A case of a patient with the diagnosis of malignant stromal tumor in transverse colon is presented, who had as the main clinical features abdominal pain, transanal hemorrhage and finally intestinal occlusion. He was submitted to exploratory laparotomy finding a transverse colon intussusception, which was treated with an extended right hemicolectomy and a post surgical satisfactory recovery. Follow-up to three years hasn't found tumoral activity. CONCLUSIONS: Stromal tumors are rare in colon, treatment is a wide surgical resection with curative or palliative purposes.

Epithelioid and spindle-celled leiomyosarcoma of the heart. Report of 2 cases and review of the literature.

BACKGROUND: Primary cardiac leiomyosarcomas are rare. Isolated reported cases and small series generally describe spindle-celled, high-grade tumors with poor short-term survival; however, the pathologic features of many of these tumors are incompletely documented. The authors report in detail the clinicopathologic features of 2 relatively low-grade epithelioid and spindle-celled primary cardiac leiomyosarcomas. METHODS: Cases 1 and 2 were studied using standard histochemical and immunohistochemical techniques, and case 1 was examined by electron microscopy. The literature was reviewed with regard to primary cardiac leiomyosarcomas. RESULTS: Both tumors showed epithelioid and spindle-celled areas. The tumor in case 1 was low grade, and the tumor in case 2 was predominately low grade with a high-grade focus. A review of 28 reported cases revealed a wide age range (mean, 43 years), equal male-to-female ratio, and a predilection for the left atrium (48%). Follow-up of reported cases with fewer than 5 mitoses per 10 high-power fields showed a mean survival of 22 months compared with a 9-month mean survival for all others. CONCLUSIONS: Short-term follow-up of reported cases of high-grade cardiac leiomyosarcoma suggests a poor prognosis. Long-term follow-up in our case 2, along with follow-up of reported cases that were histologically similar to our cases, suggests that cardiac leiomyosarcomas with low-grade features or mixed low- and high-grade features also have a poor overall long-term survival, with a high rate of local recurrence and systemic spread.

Tumor estromal maligno de colon transverso. Informe de un caso / Malignant stromal tumor of transverse colon

Antecedentes. Los sarcomas de colon son poco comunes, de ellos, el más frecuente es el leiomiosarcoma. A la fecha se han informado 45 casos de tumor estromal maligno en la literatura mundial. La histogénesis de estas neoplasias mesenquimatosas se determinan con análisis ultraestructural y tinciones de inmunohistoquímica, sin embargo, cuando estas técnicas especiales son negativas y existe duda en cuanto a la línea de diferenciación celular (músculo liso, neural o indiferenciado), es preferible llamarlos tumores estromales del tracto gastrointestinal (TEGI). Objetivo. Presentar un caso de tumor estromal maligno del colon transverso. Método. Se revisó el caso de un paciente de 46 años de edad con diagnóstico de tumor estromal maligno de colon transverso y el tratamiento efectuado. Resultados. Se informa el caso de un paciente con diagnóstico de tumor estromal maligno en el colon transverso, cuyas principales manifestaciones clínicas fueron dolor abdominal, hemorragia transanal, y finalmente oclusión intestinal. Se sometió a laparotomía exploradora, encontrando intusucepción del colon transverso, por lo que se hizo hemicolectomía derecha ampliada. La evolución postquirúrgica fue satisfactoria y la vigilancia a tres años no ha demostrado datos de activación tumoral. Conclusiones. Los tumores estromales de colon son raros y su tratamiento es la resección quirúrgica con fines curativos o paliativos

Cutaneous malignant epithelioid neoplasms.

In summary, cutaneous malignancies with an epithelioid appearance form a diverse group of neoplasms that may be difficult to diagnose by utilizing routine microscopy alone. Cutaneous malignancies, including malignant melanoma and metastatic carcinoma, certain benign neoplasms such as mixed tumor of the skin and angiolymphoid hyperplasia with eosinophils (epithelioid hemangioma), and infectious conditions such as bacillary (epithelioid) angiomatosis can be considered in this differential. However, through recognition of the characteristic histologic, immunocytochemical, and ultrastructural findings outlined above, definitive diagnosis of these challenging neoplasms is usually possible.

[Primary bone leiomyosarcoma. Anatomo-clinical, immunohistochemical, and ultrastructural study]. / Le léiomyosarcome primitif de l'os. Une observation anatomo-clinique, immuno-histochimique et ultrastructurale.

A variety of tissues in bone can be the origin of neoplastic primitive lesions. Consequently, it can be the site of various sarcomas of tissue type, incursing leiomyosarcoma. The leiomyosarcoma of the bone is considered as primitive after exclusion either a bony extension of a soft tissue tumor of vicinity or the presence of a leiomyosarcoma elsewhere. We report a case of a primary leiomyosarcoma arising on the left femur of a 40-year-old woman. The diagnosis was confirmed by immuno-histochemistry and electron microscopic study. A bloc resection followed by a prothesis was performed. The patient underwent a fractioned postoperative radiotherapy with a total dose of 75 Gy. The postoperative course one year later revealed local recurrence and pulmonary metastases. Despite the resection of pulmonary metastases and the amputation of left lower limb, the patient had developed local recurrence on the stump of amputated limb and was on the outside of all therapeutic resource. In this report, we present the clinicopathologic, immuno-histochemical and ultrastructural profiles of these rare primary bone tumors.