Evidence Of Smooth Muscle Differentiation Research Articles

Dedifferentiated leiomyosarcoma of the uterus: a clinicopathologic and immunohistochemical analysis of 23cases.

To morphologically and immunophenotypically characterize dedifferentiated uterine leiomyosarcoma (LMS). We identified 23 dedifferentiated uterine LMS, defined as a malignant uterine smooth muscle tumour containing discrete differentiated and dedifferentiated components (i.e. with and without morphologic and immunophenotypic evidence of smooth muscle differentiation, respectively). The differentiated component was leiomyosarcoma in most cases (17/23), though some arose from a leiomyoma (n=4) or smooth muscle tumour of uncertain malignant potential (n=2). The dedifferentiated tumour component showed noncohesive polygonal cells with moderate to abundant cytoplasm, pleomorphic nuclei with coarse vesicular to smudged chromatin, one or more macronucleoli, frequent multinucleation,and atypicalmitoses. Three cases showed heterologous osteosarcomatous or chondrosarcomatous differentiation. Immunohistochemistry revealed alterations characteristic of uterine LMS, including Rb loss (18/19); strong diffuse p16 (17/19); strong diffuse (9/19) or complete absence of (5/19) p53; and ATRX loss (6/16). Compared to a control cohort of uterine LMS without dedifferentiation, dedifferentiated uterine LMS showed significantly shorter disease-specific (median, 54 versus 20months; 5-year DSS, 46% versus 36%; P=0.04) and disease-free (median, 31 versus 8 months; 5-year DFS, 42% versus 8%; P=0.002) survival. Of 19 dedifferentiated uterine LMS with follow-up, 12 had died of disease at median 14 (range, 2-73)months; four were alive with disease at 4, 12, 44, and 50months; and three were alive with no evidence of disease at 56, 109, and 114months. Routine prospective recognition of dedifferentiated uterine LMS and distinction from mimics is advocated for accurate prognostication and for further characterisation of these tumours.

Spindle cell tumour with glandular elements: an unusual ileal neoplasm

This report describes a tumour in the ileum with clinical features initially suggestive of a gastrointestinal stromal tumour (GIST). Histopathological examination revealed a biphasic tumour in which the spindle cell...

Perivascular Epithelioid Cell Tumor of the Uterus: Report of Four Cases

Uterine perivascular epithelioid cell tumor (PEComa) is very rare, and there have been only 27 reported cases. The differentiation of the tumor has been enigmatic, and the biologic behavior remains unclear. This study describes the clinical, histologic, and immunohistochemical features of four cases of uterine PEComa. The patients were 30, 32, 36, and 40 years old, and none of them had tuberous sclerosis complex. The size of the tumors ranged from 1 to 30 cm in diameter, and 3 of the 4 tumors were confined in the uterus. One tumor involved the left ovary and omentum. Microscopically, the tumors were characterized by an epithelioid arrangement of tumor cells, which had abundant clear to eosinophilic pale granular cytoplasm, and one tumor had moderately atypical nuclei. Coagulative necrosis was found in two cases. The mitotic figures ranged from 0 to 11 per 10 high power fields. Immunohistochemically, the tumors were positive for vimentin (4/4), HMB45 (4/4), h-caldesmon (4/4), alpha-smooth muscle actin (3/4), muscle actin (2/4), and desmin (3/4). They were uniformly negative for Melan A, CD10, and S-100 protein. Ultrastructural examinations were performed on one case and revealed no melanosomes, premelanosomes, or evidence of smooth muscle differentiation. One patient died of intestinal metastases 17 months after surgery. The other patients have been well with no evidence of disease 8, 12, and 36 months after surgery. Uterine PEComa should be regarded as tumors with an uncertain malignant potential until long-term outcome data for a larger number of patients become available.

Expression of desmin and smooth muscle myosin heavy chain in dermatofibromas: Implications for diagnosis of dermal spindle cell tumors

c Background.—The histopathologic features of dermatofibroma vary remarkably, and this diversity may occasionally cause problems in differentiating between benign and malignant mesenchymal lesions, including smooth muscle neoplasms. Immunohistochemical stains are sometimes necessary to clarify the histogenesis of a lesion. Objective.—To evaluate dermatofibromas for expression of desmin and smooth muscle myosin heavy chain (SMMHC) antigens, which are commonly used as evidence of smooth muscle differentiation. Methods.—We studied 100 consecutive cases of dermatofibroma using hematoxylin-eosin‐stained sections and immunoperoxidase staining with antibodies against desmin, SM-MHC, and smooth muscle actin. Results.—We found focal positivity for desmin in 9 cases, and in 2 of these cases, at least 10% of lesional cells showed strong expression. We found focal staining for SMMHC in 10 cases, and in 2 of these cases, at least 10% of the lesional cells were positive. Regions positive for desmin and/or SM-MHC did not show definite histologic features of myogenous differentiation on hematoxylin-eosin‐ stained sections. All dermatofibromas expressing desmin and SM-MHC were also strongly positive for smooth muscle actin. Conclusions.—About 10% of dermatofibromas show focal expression of desmin and SM-MHC, and this expression may be present in up to 10% to 15% of lesional cells. Thus, in dermal spindle cell lesions, focal expression of these muscle antigens, like that of smooth muscle actin, is not diagnostic of a smooth muscle tumor. (Arch Pathol Lab Med. 2002;126:1179‐1183)

Expression of desmin and smooth muscle myosin heavy chain in dermatofibromas.

The histopathologic features of dermatofibroma vary remarkably, and this diversity may occasionally cause problems in differentiating between benign and malignant mesenchymal lesions, including smooth muscle neoplasms. Immunohistochemical stains are sometimes necessary to clarify the histogenesis of a lesion. To evaluate dermatofibromas for expression of desmin and smooth muscle myosin heavy chain (SM-MHC) antigens, which are commonly used as evidence of smooth muscle differentiation. We studied 100 consecutive cases of dermatofibroma using hematoxylin-eosin-stained sections and immunoperoxidase staining with antibodies against desmin, SM-MHC, and smooth muscle actin. We found focal positivity for desmin in 9 cases, and in 2 of these cases, at least 10% of lesional cells showed strong expression. We found focal staining for SM-MHC in 10 cases, and in 2 of these cases, at least 10% of the lesional cells were positive. Regions positive for desmin and/or SM-MHC did not show definite histologic features of myogenous differentiation on hematoxylin-eosin-stained sections. All dermatofibromas expressing desmin and SM-MHC were also strongly positive for smooth muscle actin. About 10% of dermatofibromas show focal expression of desmin and SM-MHC, and this expression may be present in up to 10% to 15% of lesional cells. Thus, in dermal spindle cell lesions, focal expression of these muscle antigens, like that of smooth muscle actin, is not diagnostic of a smooth muscle tumor.

Stromal sarcoma of the breast with leiomyosarcomatous pattern.

We report an unusual case of stromal sarcoma of the breast with leiomyosarcomatous pattern, which recurred locally and was finally treated by radical mastectomy. The tumor was composed of pleomorphic and hyperchromatic spindle-shaped cells arranged in an interdigitating fascicle. The nuclei were of moderate to severe atypia. An average of 10 mitoses per 10 high-power fields was seen. Immunohistochemically, the stromal cells were positive for vimentin and alpha-smooth muscle actin, but negative for S-100 protein, cytokeratin and desmin. The average Ki-67 (MIB1) labeling index in the stromal cells was 34%. Electron microscopic evaluation revealed further evidence of smooth muscle differentiation; stromal cells had frequently indented nuclei, well-developed rough endoplasmic reticulum, thin basal lamina and dense patch-like structures within the cytoplasm. Analysis of previous literature on 17 cases reveals mitotic activity of the tumor seemingly of little prognostic value. This case indicated difficulty in diagnosing leiomyosarcoma. The risk of local recurrence remains even if the surgical margin is free of tumor cells.

Pleomorphic adenoma with nuclear palisading arrangement of modified myoepithelial cells: histopathologic and immunohistochemical study.

Pleomorphic adenomas with a nuclear palisading arrangement of spindle-shaped modified myoepithelial cells (MMCs), suggesting the appearance of palisading leiomyoma or Antoni's A type of neurilemmoma, are quite rare, and its cytologic nature has been poorly understood. This paper reports histologic and immunohistochemical findings of palisading MMCs in two cases of pleomorphic adenoma. Histologically, foci of spindle-shaped MMCs with nuclei in a palisading arrangement were scattered in the myxoid areas. Near the large foci of spindle-shaped MMCs with nuclear palisading arrangements, tiny foci of spindle-shaped MMCs forming nuclear palisading or rosette-like arrangements were seen. Such nuclear palisading arrangements of MMCs were suggestive of differentiation or transformation of MMCs into cells that were more smooth muscle in nature, supported by occasional existence of palisading leiomyoma in the myometrium and gastrointestinal tract. However, immunohistochemical findings of palisading MMCs in pleomorphic adenoma were similar to those of non-palisading MMCs, and showed no evidence of smooth muscle differentiation; neither palisading nor non-palisading MMCs in pleomorphic adenoma expressed desmin, muscle specific actin (HHF-35), alpha smooth muscle actin, or myoglobin. The biologic significance and formative mechanism of nuclear palisading arrangement of MMCs in pleomorphic adenoma could not be determined in the present study. However, if the MMCs with nuclear palisading arrangements in pleomorphic adenoma, presented here, are aspirated for cytologic diagnosis or are included in a small biopsy specimen, the correct diagnosis of pleomorphic adenoma may be confused by a suspicion of myogenic or neurogenic tumor.

Role of Mesenchymal-Epithelial Interactions in Normal Bladder Development

Purpose To assess the role of cell-cell interactions in the development of bladder smooth muscle. Material and Methods Bladders from 14-day rat fetuses (prior to smooth muscle differentiation) were isolated and digested with trypsin to separate the mesenchyme and epithelium. Three types of specimens were prepared for grafting under the renal capsule of syngeneic adult hosts: a) intact bladder (BL) which had been isolated from fetuses of timed pregnant rats by surgical methods alone; b) bladder mesenchyme (BLM) alone (urothelium removed following trypsinization); and c) isolated BLM recombined with bladder urothelium (BLM+BLE). After 2 weeks of in vivo growth the grafts were assessed by immunocytochemical techniques for the expression of smooth muscle cells markers (actin, myosin, vinculin, laminin and desmin). The same experiments were repeated in vitro. In the final experiment, the induction of bladder smooth muscle was elicited in situ across species lines. Fourteen-day rat BLM was grafted onto the proximal ureter of an athymic nude mouse after ipsilateral nephrectomy. Results Grafts of intact BL and BLM+BLE recombinants expressed smooth muscle differentiation. In contrast, grafts of BLM alone remained devoid of smooth. This was also true for the in vitro studies in which, after 5 days of growth, BLM + BLE recombinants (n = 12) showed clear evidence of smooth muscle differentiation. In contrast, cultures of BLM alone (n = 12) exhibited poor growth without smooth muscle differentiation. In the final experiment testing the induction of smooth muscle across species, after 1 month in vivo growth the urothelium of the cut end of the ureter had invaded the grafted BLM. The BLM grafts (n = 3) had increased 30 times in size, and immunocytochemical staining showed clear expression of smooth muscle markers in the grafted BLM in proximity to the urothelium. Conclusion We have shown that the differentiation of smooth muscle in the rat bladder is dependent upon an inductive interaction with the epithelium.

CD34 expression by gastrointestinal tract stromal tumors

Gastrointestinal stromal tumors (GISTs) are neoplasms arising in the wall of the gastrointestinal tract that frequently show evidence of smooth muscle differentiation, either by their appearance alone or by immunohistology. A significant number of these neoplasms fail to react with any markers of muscle differentiation, however. A subset of these neoplasms have epithelioid features, and the presence of these features can give rise to confusion with other neoplasms, such as carcinomas and melanomas. Here we show that the CD34 monoclonal antibody My10 reacts with 19 of 23 (83%) of these lesions, including both those with and without epithelioid features. Five of 10 epithelioid and one of 13 spindled neoplasms lacked detectable muscle-specific actin (MSA), smooth muscle actin (SMA), and desmin; all six were CD34 reactive. Immunoblotting experiments show that the antigen on these stromal neoplasms has a molecular weight identical to that found on hematopoietic cells. The frequency and intensity of the reactivity of GISTs with anti-CD34 antibodies are distinctly higher than those reported for smooth muscle neoplasms of soft tissue and myometrium. This reactivity can be a useful adjunct in the diagnosis of difficult cases, especially in those exhibiting epithelioid morphology.

The immunohistochemistry of gastrointestinal stromal tumors. Evidence supporting an origin from smooth muscle.

To study the histogenesis of gastrointestinal stromal tumors, 79 cases were evaluated for desmin (DES), vimentin (VIM), and S-100 protein immunoreactivity by the avidin-biotin immunoperoxidase procedure on paraffin-embedded, Bouin's-fixed tissue sections. All tumors showed weak vimentin positivity. Trapped non-neoplastic smooth muscle and nerve twigs were often noted, particularly at the tumor periphery. Significant tumor S-100 positivity was not identified in our series. Similarly, glial fibrillary acidic protein (GFAP) immunoreactivity (performed in 11 desmin-negative tumors) was not detected within either gastrointestinal stromal tumors or enteric glial cells. Fifty-three percent (53%) of all gastrointestinal stromal tumors (GIST) displayed positive tumor cell desmin immunoreactivity. All 10 esophageal and all four colorectal tumors were diffusely desmin positive and unequivocal smooth muscle lesions. In contrast, only 17 of 37 (46%) benign and six of nine (67%) malignant gastric tumors were desmin positive. Similarly, four of 10 (40%) benign and one of nine (11%) malignant small-bowel tumors expressed desmin. Several gastric neoplasms with prominent nuclear palisading resembling schwannian Antoni A regions were nonetheless desmin positive. Epithelioid gastric tumors were more frequently desmin positive than nonepithelioid tumors; however, this positivity did not attain statistical significance. Two gastrointestinal stromal tumors that were desmin negative in paraffin-embedded material had detectable antigen in frozen sections. Gastric and small-bowel tumors measuring less than 3 cm were significantly more often desmin positive than those 3 cm or greater. We conclude that the method of fixation, tissue preparation, and immunostaining may significantly affect the expression of desmin. Although the histogenesis of gastrointestinal stromal tumors remains controversial, most of these tumors show evidence of smooth muscle differentiation.

Ultrastructural observations on smooth muscle tumors.

The ultrastructure of a series of primary and metastatic smooth muscle tumors is reviewed. Myofilaments and other smooth muscle features were present in all primary leiomyosarcomas of the soft tissues and uterus. They were also present but were less plentiful in most of the metastatic leiomyosarcomas. Electron microscopy is therefore a useful method to establish the diagnosis of a suspected leiomyosarcoma. Stromal tumors of the gastro-intestinal tract may require correlated immunocytochemical and ultrastructural studies for their identification: 9 of the 50 cases examined were positive with immunostaining for S-100 protein, and 16 tumors with epithelioid transformation did not show evidence of smooth muscle differentiation by electron microscopy.

Congenital gingival granular cell tumor with smooth muscle cytodifferentiation

Congenital epulis of the newborn is a rare benign congenital gingival granular cell tumor (GGCT) of unknown histogenesis which occurs most commonly on the gingiva of the anterior maxillary alveolar ridge in girls. The granular cells in this entity are histologically indistinguishable from those in extragingival granular cell tumors, known historically as granular cell myoblastoma (GCM), which occur at any age and appear to be of Schwann cell origin. Ultrastructural, histochemical, and immunohistochemical features of three GGCT were examined and compared to three GCM and a granular cell ameloblastoma. This is the first instance in which the ultrastructure of granular cells in a congenital epulis showed evidence of smooth muscle differentiation. Carcinoembryonic antigen-like immunoreactivity was localized in granular cells from all granular cell tumors studied, but S-100 protein was present only in GCM. The smooth muscle ultrastructural features and the lack of S-100 protein in GGCT strongly suggest a different histogenesis from that of GCM. The GGCT is likely derived from a primitive gingival perivascular mesenchymal cell with the potential for smooth muscle cytodifferentiation.