Pelvic inflammatory myofibroblastic tumor mimicking a rectal cancer

We report a case of a 50-year-old woman who presented to the emergency department with large bowel obstruction and anemia. The initial imaging study suggested an inoperable rectal tumor with involvement of surrounding structures. In this paper, we discuss the diagnostic work-up of this patient with a diagnosis of pelvic/ perirectal inflammatory myofibroblastic tumor (IMT). IMT is a rare tumor with intermediate malignant potential that frequently mimics clinical and imaging features of malignancy. Additionally, to the best of our knowledge, this is the first case of a pelvic IMT that regressed without surgical excision (AU)

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[Immunohistochemical and genetic profiles of melanomas with spindle cell morphology].

OBJECTIVE: to comparatively study the immunohistochemical profile and to analyze mutations in the BRAF and N-RAS genes. MATERIAL AND METHODS: The spindle cell melanomas taken from the Institute's archives were divided into 6 groups according to the results of clinical and morphological analyses and follow-up studies. Immunohistochemical examination was conducted in 58 cases, including 19 nodular spindle cell melanomas, 10 superficial spreading melanomas, 4 combined melanomas, 8 sarcoma- toid melanomas, 13 mixed desmoplastic melanomas, and 4 pure desmoplastic melanomas. RESULTS: All tumors of the spectrum in question expressed S100, SOX10, KBA.62, nestin, and cyclin D1. The rate of positive staining was 80% for MITF, 69% for PNL2, 61% for HMB45, 58% for Melan A, 36% for CD117, and 35% for SMA. The expression of HMB45 and Melan A was diffuse and marked in the groups of nodular and superficial spreading melanomas; sarcomatoid and mixed desmoplastic melanomas showed only scattered stained cells; pure desmoplastic melanomas were negative to these markers. SMA immunoexpression was observed in only sarcomatoid and desmoplastic types. Dual S100 staining showed a separate actin-positive myofibroblast-like population disappearing in more cellular zones. EMA, claudin 1, and DOG1 were negative in all cases. BRAFV expression was detected in 14% (in 2 nodular and 1 superficial spreading melanomas) and correlated with the presence of mutation. NRAS mutation was found in 1 nodular spindle cell melanoma. Desmoplastic melanomas did not harbor the above mutations. CONCLUSION: This study indicates the variant heterogeneity of spindle cell melanomas, as confirmed by clinical, morphological, immunohistochemical, and molecular examinations. The findings may be useful in the differential diagnosis of these tumors.

Pleomorphic spindle cell dermal neoplasm with dot-like keratin reactivity: keratin-positive AFX or carcinoma?

Atypical fibroxanthoma (AFX) is an uncommon cutaneous neoplasm of pleomorphic myofibroblast-like cells. Diagnosis requires exclusion of other undifferentiated spindle and pleomorphic cell neoplasms by immunohistochemistry. We report two patients with p63-non-reactive spindle cell neoplasms which resembled AFX but demonstrated anomalous dot-like immunolabeling with antibodies to high molecular weight keratin and keratin 5. One case recurred locally, suggesting such lesions may behave aggressively. Whether these lesions represent keratin-positive dermal sarcomas or poorly differentiated carcinomas is debatable. Regardless of exact classification, our experience suggests such cases should be managed as high-risk non-melanoma skin cancers.

Down-regulation of miR-221 and miR-222 correlates with pronounced Kit expression in gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs), are characterized by mutations of the KIT or platelet-derived growth factor receptor-α gene and the constitutive expression of Kit, which is currently being studied as a potential therapeutic target. In this study, we addressed the question of whether the microRNA (miRNA) 221/222 cluster (miR-221/222), which has been shown to be dysregulated in many malignancies, is linked to GIST diagnosis and prognosis, and whether it could provide a basis for possible therapeutic approaches. We analyzed the expression of miR-221 and miR-222 in 54 formalin-fixed and paraffin-embedded GISTs and corresponding peripheral non-tumorous tissue by real-time PCR. The miRNA-expression levels were studied in relation to histomorphological parameters, KIT mutation status and immunohistochemical Kit expression. miR-221 and miR-222, were reduced in most of the GISTs, in contrast to other tumors. No correlation was observed between miR-221/222 expression levels and histomorphological parameters, tumor risk grade, or KIT mutation status. However, we found major differences in miRNA expression among the different groups of immunohistochemical Kit expression, especially between Kit-negative and -positive tumors. The expression levels of miR-221 and miR-222 were significantly repressed in Kit-positive GISTs, compared to normal tissue, whereas Kit-negative GISTs exhibited a completely inverse expression pattern. This study shows for the first time that miR-221 and miR-222 can act as regulators of Kit expression in GISTs and hence reveals a new aspect in the molecular pathogenesis of these tumors. Although miR-221/222 expression does not have an impact on diagnostics, it could be considered as a tool for future therapeutic strategies for GISTs, especially for tumors with secondary resistance to tyrosine kinase inhibitors.

The staining pattern of pigmented spindle cell nevi with S100A6 protein.

BACKGROUND: Spitz nevi typically show strong diffuse staining with S100A6, whereas staining in melanomas is commonly patchy and weak. To our knowledge, S100A6 has not been studied in pigmented spindle cell nevus (PSCN), considered by many to be a variant of Spitz nevus. METHODS: Forty-six archived PSCNs were stained with S100A6 and then categorized by predominant cell size and staining pattern. RESULTS: Eighteen (55%) of the small cell predominant nevi showed patchy staining, eight showed diffuse staining and seven were negative for S100A6. Two predominantly large-celled 'PSCNs' were diffusely positive and had many histopathological attributes of classical Spitz nevi. On review, these two cases were reclassified as Spitz nevi and excluded from the remainder of this study. Of the nevi with mixed cell size, one had no expression of S100A6. In the remaining tumors, the small cells showed patchy staining in eight (80%) and diffuse staining in two (20%). The large cells showed patchy staining in four (40%) and diffuse staining in six (60%). CONCLUSION: In contrast to the strong diffuse S100A6 staining typical of Spitz nevi, the small spindle cells of PSCN commonly show patchy staining or fail to stain completely. In melanocytic neoplasms composed of small spindle cells, patchy S100A6 staining should not be interpreted as evidence of supporting a diagnosis of melanoma.

Cellular angiofibroma is genetically similar to spindle cell lipoma: a case report.

Cellular angiofibroma is a benign mesenchymal neoplasm of female and male genital tract composed of prominent vasculature and stromal spindle cells, often with admixture of adipose tissue. The tumor has histomorphologic similarities to angiomyofibroblastoma and spindle cell lipoma. Herein we describe a tumor arising in the perineal region of a 60-year-old man with morphological and immunohistochemical features of cellular angiofibroma and showing cytogenetic characteristics similar to spindle cell lipoma. To our knowledge, this is the first report of cytogenetic changes in cellular angiofibroma. The genetic overlap of these entities supports their origin from the same mesenchymal stem cell.

Gastrointestinal stromal tumors: a clinicopathologic and immunohistochemical study of 136 cases.

The clinicopathologic features of 136 gastrointestinal stromal tumors were analyzed. The tumors occurred in 60 women and 76 men, ranging in age from 19 to 88 years (median 59 years, mean 59.2 years). Sixty-one cases arose from stomach, 38 from small intestine and 11 from colon or rectum. Abdominal cavity was indicated as tumor site in 10 cases, but the extra-gastrointestinal origin using strict criteria was not proved. Four locally recurrent cases and 12 metastatic samples were also included. The primary and recurrent tumors ranged in size from 0.5 to 30 cm (mean 8.3 cm). The large number of high-grade cases (85 of 112 classifiable) is alarming and emphasize the importance of oncology care. Histologically, ninety-two cases were classified as spindle cell while 11 as epithelioid GIST. Mixed cellularity was seen in 33 cases. Skeinoid fibers were present in 14 and coagulation necrosis in 40 primary cases. Ulceration observed by microscopic examination was common (36 of 110 cases, 32.7%), explaining the clinically frequently observed gastrointestinal bleeding. Unusual histological features such as stromal hyalinization and nuclear palisading were present in 30 and 27 cases, respectively. Immunohistochemical CD117 (c-kit) positivity was documented in 133 cases. Three cases with CD117 negative results were included, because their morphology was most consistent with GIST and immunohistochemical reactions excluded the possibility of other neoplasms. CD34 positivity was seen in 70%, alpha-smooth muscle actin positivity in 39.6% of examined cases. Only one case showed desmin reactivity and seven had S100 positive tumor cells. For h-caldesmon 39 cases proved to be positive (60.9% of the tested cases).

BRAF mutations are detectable in conjunctival but not uveal melanomas.

Activating mutations in exon 15 of BRAF have been detected in a high proportion of cutaneous melanomas. To determine whether such mutations are a feature of conjunctival or uveal melanomas, we screened DNA from these tumours. Twenty-one conjunctival and 88 uveal tumours were included in the study. Mutation analysis of BRAF exons 11 and 15 was undertaken using a combination of conformationally sensitive gel electrophoresis and direct sequencing. Mutations in exon 15 were detected in three of the conjunctival tumours (two V599E and one E585 K). None of the uveal tumours possessed a BRAF mutation in either exon 15 or 11. We conclude that uveal melanomas arise independently of oncogenic BRAF mutations, but the development of a proportion of conjunctival tumours involves mutation of this gene.

Chromosomal abnormalities, p53 and Bcl-2 expression and clinical outcome in choroidal melanoma.

OBJECTIVE: To determine whether alterations of p53, Bcl-2 and chromosomes were present in choroidal melanoma and to further characterize the prognosis of these changes. METHODS: The expression of p53 and Bcl-2 protein was assessed by immunohistochemistry from paraffin blocks. Tumours were analysed by comparative genomic hybridization (CGH) to identify chromosomal aberrations. Fifteen tumours were studied, and the survival results were compared by Spearman correlation analysis with a mean follow-up of 36.5+/-8 months. The majority of tumours were mixed (eight cases), and the others were spindle cell (four cases) and epithelioid cell (three cases) types. Four patients have already died due to metastatic disease. RESULTS: p53 was expressed at a low percentage in only two tumours. There were no differences in Bcl-2 expression in our cases. Bcl-2 was expressed by the majority of cells in all cases. Chromosomal copy number aberrations were detected in 10 of the 15 patients by CGH analyses. A gain at chromosome 8 and a loss at chromosome 3 were the most frequently seen abnormalities. The other aberrations observed were losses at 6q, 7q14 and 17p13-15, and gains at 6p and 18q. Two of the three cases with a loss at 17p13 showed a low percentage expression of p53. No relationship was determined between the chromosomal abnormalities, cell type, expression of p53 and survey. The presence of a chromosome 6q deletion in two of the four patients who died of metastatic disease may indicate that chromosome 6q deletion may be correlated with a poor prognosis. CONCLUSIONS: Our results suggest that choroidal melanomas show high levels of chromosomal alterations. Further studies are necessary to determine the correlation between chromosomal abnormalities and prognosis.

Pigmented spindle cell naevus of reed presenting in the conjunctiva.

PURPOSE: This study aimed to present the clinical and histopathological features of a pigmented spindle cell naevus (PSCN) appearing in the conjunctiva. METHODS: Histopathological examination of the lesion following excision and review of the pertinent literature. RESULTS: The features were consistent with those previously recognized in the skin as the PSCN of Reed. CONCLUSION: The PSCN can appear in the conjunctiva and should not be confused with conjunctival melanoma.