Giulio Bigotti

Galectin-3, a marker of well-differentiated thyroid carcinoma, is expressed in thyroid nodules with cytological atypia.

Galectin‐3, a marker of well‐differentiated thyroid carcinoma, is expressed in thyroid nodules with cytological atypia

Immunohistochemical expression of the glucose transporters Glut-1 and Glut-3 in human malignant melanomas and benign melanocytic lesions

BackgroundReported data indicate that cancer cells have increased rates of glucose metabolism, as determined by 18FDG-PET imaging in patients with malignancies. The results of many studies have demonstrated that the expression of glucose transporters, especially Glut-1, is increased in a variety of malignancies. This study was undertaken to assess the differential expression of Glut-1 and Glut-3 by benign and malignant melanocytic lesions.MethodsImmunohistochemical staining for Glut-1 and Glut-3 was performed on paraffin-embedded tissue sections prepared from melanocytic nevi (12 cases), Spitz nevi (12 cases) and primary cutaneous malignant melanomas (20 cases).ResultsWe observed immunoreactivity for Glut-1 in all melanocytic nevi, 9 of the 12 Spitz nevi and in 9 of the 20 malignant melanomas, whereas Glut-3 was expressed in all the melanocytic lesions, both benign and malignant.ConclusionThese findings indicate that the glucose transporters Glut-1 and Glut-3 play a role in the glucose metabolism of melanocytic cells. Glut-1 was present in the majority of benign nevi, whereas its expression was downregulated in 55% of malignant melanomas. Our results suggest that glucose transporter Glut-1 expression can significantly discriminate between human malignant melanoma and benign melanocytic nevi, and support the idea that additional mechanisms other than Glut-1 may contribute to glucose uptake in melanomas.

Sarcomatoid carcinoma of the adrenal gland: A case report and review of literature.

Reports about adrenocortical carcinomas (AC) mixed with sarcomatous areas are very rare. The terminology and pathogenesis of such biphasic tumors remain controversial. Herein, we report a case of sarcomatoid carcinoma of the adrenal gland in a 75-year-old woman who presented with left abdominal pain of one months standing. The results of abdominal ultrasonography and computed tomography (CT) showed the presence of a large heterogeneous adrenal mass. A left adrenalectomy and complete splenectomy were performed. Histologically, the neoplasm showed areas of adrenocortical carcinoma and areas of sarcomatoid spindle cell proliferation. When examined immunohistochemically, the carcinomatous cells stained positively for S-100 protein, Melan-A protein, and neuron-specific enolase (NSE), and focally for vimentin and the cytokeratin marker MNF 116. Also, the carcinomatous cells were immunoreactive to the monoclonal antibody HMB-45. The sarcomatous component expressed vimentin, as well as other smooth and skeletal muscle markers. Liver metastases appeared 3 months postoperatively. Twelve months after removal of the primary tumor, the patient died of her disease. To the best of our knowledge, only seven cases of adrenal sarcomatoid carcinoma have been reported in the medical literature. We review the reported cases according to the 2004 classification of the World Health Organization (WHO) of lung tumors, and highlight the histogenesis, diagnosis, and clinical course of this very aggressive tumor.

Angiomyofibroblastoma and aggressive angiomyxoma: two benign mesenchymal neoplasms of the female genital tract. An immunohistochemical study.

We describe a rare case of angiomyofibroblastoma (AMF) of the vulva and one case of aggressive angiomyxoma (AAM) of the pelvic region and, with the help of an extensive revision of the literature, we attempt to define their histogenesis and peculiar biological behaviour by an immunohistological evaluation. Our results indicate that AAM, which is characterized by the presence of a high content of glycosaminoglycans in the stroma, expresses uniformly vimentin and hyaluronate receptor CD44, and heterogeneously muscle specific actin (MSA) and desmin, while AMF displays a positive reaction for vimentin, desmin and laminin, and only a weak and heterogeneous positivity for CD44. Both AMF and AAM showed no immunohistochemical reactivity for alpha-smooth muscle actin (ASMA), myoglobin, cytokeratin, collagen type IV, CD68 and S-100. The stromal cells of AAM were negative for laminin. These findings support the suggestion of an origin of the two entities by a common myofibroblastic progenitor, which normally occurs in the lower female genital tract and subsequently undergoes a neoplastic transformation. The expression of CD44 by AAM, which has never been reported before, could be responsible for its more aggressive behaviour, because this receptor is able to mediate migration of neoplastic cells on a hyaluronate rich extracellular matrix. It is speculated that the neoplastic cell of the AAM and AMF of the vulva is a specific myofibroblast which probably arises from undifferentiated mesenchymal cells normally occurring in the lower female genital tract.

Hamartomatous sialolipoma of the submandibular gland: case report.

Sialolipoma is a rare tumour of the salivary gland that is composed of mature adipocytes and normal salivary gland tissue. We report an unusual case of a sialolipoma of the submandibular gland in a 77-year-old woman. The location of this tumour has not to our knowledge been previously described. The tumour was excised and has not recurred during 22 months postoperatively.

Heterogeneous distribution of actin, myosin, fibronectin and basement membrane antigens in primary and metastatic human breast cancer

The distribution of actin, myosin, fibronectin and basement membrane antigens has been studied by indirect immunofluorescence in benign and malignant human breast lesions. While benign tumors showed only minor differences from normal mammary tissue, tumors of different histological types displayed a heterogeneous distribution of the antigens studied. Heterogeneity was observed within the same tumor, among different neoplasms and between primary tumors and autologous metastases. As a common characteristic, most of the tumors did not stain for actin and myosin, the pattern being similar to that found in myoepithelial cell distribution. In transformed epithelia there was often a lack of detectable actin with a myosin-positive fluorescence. Staining for both proteins was diffused to most of the cell cytoplasm. Staining for fibronectin was seen in only a minority of the cases, with medullary tumors being the most positive. Basement membrane stain was either absent or decreased and fragmented, except in rare ductal, i.e. papillary, carcinomas. Medullary tumors displayed an almost continuous, though fragmented basement membrane in approximately 70% of cases.

Histiocytosis X arising in Hodgkin's disease: immunophenotypic characterization with a panel of monoclonal antibodies

This report describes the antigenic profile of the proliferating cells of pulmonary histiocytosis X (HX) in a patient treated with chemotherapy for Hodgkins lymphoma; the association of pulmonary HX and Hodgkins disease has rarely been described in the literature. The histopathological diagnosis of HX was confirmed with the aid of monoclonal antibodies (mAbs) to CD4, CD1a, and polyclonal serum anti S-100 protein. The phenotype of HX cells has been analysed using a panel of mAbs against HLA class I A, B, C monomorphic determinants, locus A and B,β2-microglobulin, HLA class II distinct monomorphic determinants, DP, DQ, DR, intercellular adhesion molecule-1 (ICAM-1) and vitronectin receptors. Our results indicate that HX cells express HLA class I and II, including locus A, locus B and DP, DQ, DR, like their normal counterpart (represented by Langerhans cells) and detectable levels of ICAM-1 but not vitronectin receptors. We would like to stress the possibility of the association of HX and Hodgkins lymphoma extending the immunophenotypic profile of HX cells.

Synchronous Bilateral Testicular Germ Cell Tumor with Different Histology

A rare case of synchronous bilateral testicular germ cell tumor of different histological type is described. We report the case of a 39-year-old man with this unusual condition and discuss the value of the histopathological diagnosis in therapy and prognosis. A thorough review of the literature is also presented, and for the first time the precise histological subtype of each reported tumor, as diagnosed by the authors of the original paper, is illustrated.

Gastric adenocarcinoma associated with granulomatous gastritis. Case report and review of the literature.

Aims We describe the fourth reported case of granulomatous gastritis associated with gastric adenocarcinoma, with a review of the literature and considerations about the prognostic implications of this association. Results A 48-year-old woman who had been suffering from gastritis for ten years was admitted to our institute for increasing left epigastric pain associated with vomiting. After an endoscopic biopsy had revealed an ulcerated signet ring cell carcinoma, the patient was submitted to subtotal gastrectomy with regional lymph node dissection. Pathological examination of the resected specimen revealed a superficial signet ring cell carcinoma (early cancer) associated with multiple granulomas. The granulomas, which were observed within the mucosa and the submucosa at the periphery of the carcinoma, were composed of CD68-positive, CD15-negative epithelioid and giant cells of the Langhans type, confirming their true histiocytic nature, and were also extensively found within the dissected lymph nodes. Since no ocular, skin, pulmonary or other gastrointestinal lesions were found and the granulomas were negative for acid-fast and fungal stain, a diagnosis of granulomatous gastritis was made. Conclusions To the best of our knowledge this is the fourth example of gastric adenocarcinoma and granulomatous gastritis. These cases suggest an association between granulomatous gastritis and early gastric cancer.

An unusual case of metaplastic breast carcinoma following neoadjuvant chemotherapy.

To the Editor: Metaplastic breast carcinomas (MBCs) are a rare and heterogeneous group of breast carcinomas. MBCs often display extensive metàplasis, a Greek word that was introduced by Virchow to describe a transformation, in which a cell type changes into another cell type. Accordingly, squamous, spindle cell, and/or mesenchymal differentiation are frequently found in parts or all of the carcinomatous epithelium of an MBC. Although the results of recent genetic studies support a monoclonal origin of the heterogeneous components of a metaplastic tumor, the mechanisms that underlie metàplasis are unknown. Here, we report a case of MBC following neoadjuvant chemotherapy (NAC). The patient was a 65-year-old woman who presented with a palpable mass in the upper lateral quadrant of her right breast. The results of the clinical, ultrasound, and mammographic examinations showed the presence of a dense tumor (4 cm ¥ 3 cm ¥ 3 cm) in the upper outer quadrant of her right breast with no involvement of the axillary nodes. After fineneedle aspiration cytology and core needle biopsy of the breast tumor, the woman was diagnosed as having an invasive ductal, not otherwise specified (NOS), carcinoma (Fig. 1a). When the tumor was immunohistochemically stained for biomarkers, the cells were estrogen receptor (ER) and human epidermal growth factor receptor-2 (HER-2) positive, and progesterone receptor (PR) negative. Neoadjuvant chemotherapy that comprised herceptin, epidoxorubicin, and taxol was then started for two months. At the end of the treatment period, the entire tumor and the axillary lymph nodes were removed by radical mastectomy and axillary lymph node dissection. The postoperative pathological stage for this patient was T2 N0 M0, IIA. After surgery, the patient did not receive any additional chemotherapy or radiation therapy, and was disease-free, 17 months after surgery. Gross examination of the surgically-resected tumor showed a firm and whitish lesion which measured 3 cm ¥ 2 cm ¥ 1.5 cm. Microscopically, the neoplasm was predominantly composed of nodular areas whose peripheries were lined by poorly differentiated basaloid or spindle-shaped carcinomatous cells, and in which progressive squamous epithelial differentiation toward the center was present (Fig. 1b). The squamous component was well-differentiated, and keratinization with prominent pearl formation was evident. Some of the intraductal lesions were cystic with keratinized debris in a large central lumen. Focal tubular gland formation was present. Ductal-squamous transition (Fig. 1c) and cells with a clear cytoplasm and without any obvious signs of keratinization were seen in the nodule’s central region. Mitoses were scanty. The nodules showed both pushing non-infiltrative borders, as well as stromal invasion. An invasive component with very discernible squamous differentiation was also seen (Fig. 1d). Prominent desmoplasia was present in the peritumoral stroma, and lymphocytes were scattered in the stroma at the tumor edge. No vascular or neural invasion of the tumor was observed, and the neoplasm did not involve the overlying skin. Cytoplasmic vacuolization was seen in some of the residual normal ducts. Immunohistochemically, the neoplastic cells of the excised tumor were positive for high molecular weight cytokeratins (CKs) 5/6 (Fig. 2a) and 14, the broad-spectrum CK, MNF 116, tumor protein p63 (Fig. 2b), epithelial membrane antigen, and epidermal growth factor receptor (EGFR). Positive reactivity for CK7 was restricted to the neoplastic tubular structures, and negative reactivity for CK7 was observed in the poorly differentiated cells, the most mature keratinized cells, and the keratin pearls. The stromal myofibroblastic cells that surrounded the neoplastic areas were positive for vimentin and smooth muscle actin. Focal vimentin positivity was also observed throughout the excised tumor. Also, the neoplastic cells were ER negative, PR negative, and HER-2 negative, and had a high Ki-67 proliferation rate. We made a final pathological diagnosis as an invasive and intraductal metaplastic adenosquamous carcinoma whose surgical margins were free of neoplastic involvement. Each of the 30 resected lymph nodes from the right axilla was negative for the cancer. Metaplastic breast carcinomas can be classified into subtypes according to their phenotypic appearance. The clinical features and radiological appearance of MBCs are not different from those of infiltrating ductal NOS carcinoma. According to reports, the median size of an MBC is larger than that of ordinary carcinoma of the breast, and metastases to the axillary nodes are relatively uncommon. However, some authors have commented that the advanced stage and lymph node involvement are associated with a behavior which is more aggressive than that of ordinary invasive ductal carcinoma of the breast. Although there are literature reports that most ductal carcinomas display different tissue responses after NAC, features of metàplasis have not yet been reported for an excised tumor after chemotherapy. The only post-treatment histological change that we observed in the excised tumor was cytoplasmic vacuolization in rare normal ducts. Pathology International 2012; 62: 72–74 doi:10.1111/j.1440-1827.2011.02750.x