Antonietta Torrisi

Intrarenal Solitary Fibrous Tumor of the Kidney: Report of a Case with Emphasis on the Differential Diagnosis in the Wide Spectrum of Monomorphous Spindle Cell Tumors of the Kidney

Solitary fibrous tumor (SFT) is a neoplasm that can occur in the urogenital tract, and is also reported occurring in the spermatic cord, seminal vesicles, urinary bladder, prostate, and kidney. Furthermore, it is most important to consider its existence in the kidney, because it is usually diagnosed as renal cell carcinoma pre-operatively. To our knowledge, only 10 cases of SFT have been reported in the kidney to date. We report the clinico-pathological features of an intrarenal SFT occurring in a 31-year-old woman. The tumor, measuring 8.6 cm in its greatest diameter, completely replaced the cortex and the medulla of the middle region of the right kidney, compressing the pelvis. Radiological imaging was consistent with a renal cell carcinoma. Histologically, the tumor was composed of a proliferation of bland-looking vimentin+, CD34+, bcl2+ and CD99+ spindle cells exhibiting a haphazard to storiform growth pattern, pushing borders, and a low mitotic rate (2 mitoses x 10 HPF). We placed emphasis on the differential diagnostic problems, i.e., its differentiation from other primary monomorphous benign and malignant spindle cell tumors of the kidney, such as fibroma, benign fibrous histiocytoma, hemangiopericytoma, inflammatory myofibroblastic (pseudo-)tumor, leiomyoma, angiomyolipoma with predominant spindle cell smooth muscle component, benign peripheral nerve sheath tumors, renal mixed epithelial/stromal tumors, adult type mesoblastic nephroma, fibrous type monophasic synovial sarcoma, malignant peripheral nerve sheath tumors, fibrosarcoma, and low-grade fibromyxoid sarcoma.

Aberrant expression of TfR1/CD71 in thyroid carcinomas identifies a novel potential diagnostic marker and therapeutic target.

BACKGROUND Type I receptor for transferrin (TfR1/CD71) is overexpressed in several malignant tumors, but no studies are available on thyroid carcinomas. Our previous comparative analyses of the relative distribution of transferrin in benign versus papillary thyroid carcinoma (PTC) tissues highlighted a marked malignancy-associated abundance of the molecule. The aim of the present study was to evaluate whether TfR1/CD71 is also differentially expressed in benign versus malignant thyroid tissues. METHODS Tissue samples, including benign lesions and follicular-derived carcinomas, from 241 patients and a total of 35 benign and malignant fresh specimens were assayed for TfR1/CD71 expression by reverse transcriptase-polymerase chain reaction, Western blot, and immunohistochemistry. RESULTS We found that transcription of TfR1/CD71 gene is constitutive in thyroid epithelia, but the mRNA is differently translated in benign and malignant tissues. Western blot revealed higher levels of TfR1/CD71 protein in malignant versus benign tissues. Immunohistochemically, most carcinomas exhibited overexpression of the receptor, predominantly in the cytoplasm of neoplastic cells. The highest expression level was detected in primary and metastatic papillary carcinomas and anaplastic carcinomas, with positive results ranging from 86% to 100% of the cases. In contrast, most benign tissues were negative, with only a minority of cases showing focal and weak immunoreactivity. CONCLUSIONS Our findings suggest that altered expression of TfR1/CD71 may be used as a marker helpful in distinguishing PTC from papillary hyperplasia and follicular variant PTC from benign follicular-patterned lesions. Additionally, the present observations support the rationale for the use of radiolabeled transferrin/transferrin analogs and/or anti-TfR1/CD71 antibodies for diagnostic and/or radiotherapeutic purposes in TfR1/CD71-expressing thyroid tumors.

Myofibroblastoma of the Breast with Hemangiopericytoma-like Pattern and Pleomorphic Lipoma-like areas : Report of a Case with Diagnostic and Histogenetic Considerations

Myofibroblastoma (MFB) of the breast is an uncommon benign spindle cell tumor which may exhibit a wide spectrum of histological features. We report an unusual case of MFB of the male breast, showing cellular areas with a hemangiopericytoma-like pattern similar to that observed in solitary fibrous tumor (SFT) and extensive fibromyxoid areas containing numerous atypical stromal cells. The association of these atypical cells with mature adipocytes and microcystic and/or myxoid degenerative changes resembled pleomorphic lipoma-like and myxoid liposarcoma-like features, respectively. To our knowledge, these peculiar morphological findings have not been previously reported in MFB of the breast. They should be recognized to avoid confusion with other mesenchymal tumors, especially with hemangiopericytoma, pleomorphic lipoma (PL), spindle-cell lipoma (SCL) and myxoid liposarcoma. A case of MFB of the breast showing morphological features also commonly seen in SFT and PL/SCL is further morphological evidence in support of the speculation that the mesenchymal tumors of the breast, also known under the terms benign spindle cell tumors, fibromas, SFTs, SCLs and MFBs, are histogenetically related lesions.

High levels of connexin 43 mRNA in high grade astrocytomas. Study of 32 cases with in situ hybridization

Gap junctions are composed of a family of evolutionarily conserved integral plasma membrane proteins termed connexins. The aims of the research reported here were (1) to evaluate the Cx43 protein and mRNA of both low histological grade and high histological grade astrocyte tumors; (2) to evaluate if the immunohistochemistry of the Cx43 protein in astrocytomas could be correlated to histological grade, to proliferative activity (Ki67/Mib1-index) and to immunolabelling of the epidermal growth factor receptor (EGFR); (3) to evaluate if the reduction in levels of the Cx43 protein correlates with reduction in levels of the Cx43 mRNA. This study showed that the immunohistochemical labelling of Cx43 is reduced in grade III and grade IV. Decreased gap junction-mediated intercellular communication corresponds to decreased Cx43 and increased cellular proliferation rates, as measured by immunolabelling of the Ki67 nuclear antigen. This study demonstrated also the persistence in high grade astrocytomas of elevated levels of Cx43 mRNA. The reduced levels of Cx43 protein should not to be ascribed to a reduced genetic transcription, but to an alteration of the post-transcriptional mechanisms such as the regulation of its synthesis and/or the intracellular transport to membrane sites.

Correlated expression of BCL-2 protein, estrogen receptor, cathepsin D and low growth fraction (PCNA) in intracystic papillary breast carcinoma.

The expression of BCL-2 protein was evaluated immunohistochemically in 23 intracystic papillary carcinomas (IPCs) of the breast. Twenty-two patients were female and one male, aged 49-90 years (median 72). Twenty-one cases had a benign behaviour, while two cases developed local recurrence. Of the 23 tumours, 19 (82%) were immunoreactive for BCL-2, the majority of positive carcinomas showing intense cytoplasmic staining of more than 50% neoplastic cells. The intensity of BCL-2 expression was significantly correlated with prognostic markers such as estrogen receptor (ER) positivity (p = 0.001), cathepsin D (CD) reactivity in the neoplastic cells (p = 0.001) and low growth fraction, evaluated by proliferating cell nuclear antigen (PCNA) immunostaining (p = 0.008). An inverse relationship was also found between BCL-2 and p53 protein (p = 0.001). Three cases of high grade (G3) IPC expressed p53, high PCNA index, and CD (the latter only in the stromal cells), but no immunostaining for BCL-2 and ER. Thus, absence of BCL-2 expression in high grade IPC was associated with ER-negative, rapidly proliferating and p53-positive immunophenotype. All high grade tumours showed invasion of the cystic wall. Local recurrence developed in one of these. The authors conclude that BCL-2 immunoreactivity in IPC is related with tumour grade and with a range of molecular markers of favourable prognosis such as ER positive status, CD expression in the neoplastic cells, and low PCNA index. These findings are consistent with the indolent clinical course and the very favourable prognosis of IPC of the breast.

Atypical/bizarre spindle-cell epithelial metaplasia in nodular goiter: a potential diagnostic pitfall.

Sir, Primitive spindle-cell tumor or tumor-like lesions of the thyroid are an uncommon finding. As far as thyroid tumors are concerned, apart from the well-known possibility that hyalinizing trabecular adenoma and anaplastic carcinomas may contain epithelial spindle cells, more rarely other tumors, such as follicular adenoma and papillary carcinoma, exhibit a metaplastic spindle-cell epithelial component [4]. In some primitive thyroid lesions, the spindle-cell component may be mesenchymal rather than epithelial in nature; this is the case of the solitary fibrous tumor and reactive lesions, such as the nodular fasciitis-like stroma of the papillary carcinoma and postfine-needle aspiration spindle-cell nodules [1]. Spindle-cell epithelial metaplasia with nuclear pleomorphism may be occasionally seen in follicular adenoma (atypical adenoma) and focally even in nodular goiter. We report an unusual case of nodular goiter with an area of atypical spindle-cell epithelial metaplasia. A 54-year-old man underwent total thyroidectomy for bilateral nodular goiter. An unexpected finding was the presence of a 1.5cm-sized, unencapsulated nodular area abruptly merging from an otherwise typical nodular goiter (Fig. 1A), composed mainly of spindle cells with bizarre hyperchromatic nuclei, similar to those observed in the socalled “atypical adenoma” (Fig. 1A, B, C). The cells, frequently arranged in whorls vaguely reminiscent of a nerve-sheath tumor (Fig. 1B), were set in a variably cellular fibrous to edematous stroma. Variable-sized thyroid follicles, some of which showed atypical nuclear pleomorphism, were frequently intermixed with the spindlecell component, and transition morphological features from follicles to spindle cells were focally observed (Fig. 1B). Mitoses and necrosis were not observed. Immunohistochemical analysis showed a diffuse expression of thyroglobulin and vimentin in association with focal cytokeratin immunoreactivity in atypical spindle cells (Fig. 1D, E, F), while no reaction to calcitonin, S-100 protein, CD34, desmin and a-smooth-muscle actin was obtained. The immunohistochemical and morphological features supported the follicular-derived metaplastic epithelial nature of the atypical/bizarre spindle cells, similar to what is observed in spindle-cell component arising in association with papillary carcinoma and follicular adenoma of thyroid [4]. The spindle-cell metaplastic transformation of follicular epithelium is not at all surprising if we consider that both normal and neoplastic thyroid follicular cells in vitro may undergo an epithelial–mesenchymal transition with a fibroblastic-like appearance characterized by an acquisition of vimentin expression accompanied by a concurrent variable loss of cytokeratin [2, 3]. The present case contributes to widen the spectrum of the spindle-cell lesions, which can be encountered in diagnostic practice of thyroid pathology. Although atypical follicular cells may be expected in different thyroid diseases (follicular adenoma, nodular goiter, Basedow’s disease) without adverse prognostic significance, their uncommon spindle-cell metaplastic transformation may alert pathologists, who should be aware of this possibility to avoid a diagnosis of malignancy.

An unusual case of three synchronous tumors in a young woman.

The occurrence in the same young patient of three synchronous tumors deriving from different embryogenic tissues and without a clear correlation with a common etiopathogenic factor is very unusual. We report a case of a Caucasian woman submitted to wide resection of a large retroperitoneal liposarcoma and right radical nephrectomy for suspected tumor infiltration. Histological examination of the right ureter and renal pelvis showed the presence of a multifocal urothelial carcinoma that was clinically asymptomatic. Two months later, during follow-up, chest X-ray and computed tomography documented a coin lesion of the upper left lung, confirmed by positron emission tomography. This nodule was surgically removed and examined histologically, resulting in a diagnosis of sclerosing hemangioma. The patient is alive without evidence of recurrent disease.

Paratesticular Pleomorphic Rhabdomyosarcoma in the Elderly An Immunohistochemical, Ultrastructural Study and Review of the Literature

A case of paratesticular pleomorphic rhabdomyosarcoma, presenting as an ulcerated mass in the left hemiscrotum of an 83-year-old man, is reported. By light microscopy, this neoplasm could not be distinguished from other pleomorphic sarcomas, such as malignant fibrous histiocytoma, leiomyosarcoma, and liposarcoma. Immunohistochemistry showed that most tumor cells were strongly reactive with antibodies directed against myoglobin, desmin, a-sarcomeric actin, and myogenin, whereas x-smooth muscle actin expression was less extensive. Electron microscopic examination demonstrated thick and thin filaments with condensations of electron-dense material reminiscent of structures of Z-lines in the large pleomorphic cells. On the basis of these findings, the neoplasm was classified as a pleomorphic rhabdomyosarcoma. According to a review of the literature, this is the first well-documented example of paratesticular pleomorphic rhabdomyosarcoma in an elderly person.