Giada Maria Vecchio

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.

Giant intramuscular lipoma of the tongue: a case report and literature review

We herein report a rare case of giant intramuscular lipoma of the tongue. A 75-year-old Italian male presented at our department with a large tumor at the tip of the tongue that had been present for over 30 years. Clinical examination revealed a yellowish lesion, measuring 10 cm in maximum diameter, protruding from lingual surface. Histological examination showed an unencapsulated lipomatous tumor composed of mature adipocytes, uniform in size and shape, diffusely infiltrating striated muscle fibers of the tongue. The patient is well with no local recurrence after a 15-month follow-up period.

Multinucleated floret-like giant cells in sporadic and NF1-associated neurofibromas: a clinicopathologic study of 94 cases

Multinucleated floret-like giant cells (MNFGCs), similar to those commonly observed in pleomorphic lipoma and giant cell fibroblastoma, have been occasionally reported in gynecomastia and neurofibromas from patients affected by neurofibromatosis type 1 (NF1). Accordingly, it has been suggested that their detection, especially in an otherwise typical neurofibroma, could be a morphological clue to diagnosis of NF1. The aim of the present study was the identification of MNFGCs in a large series (94 cases) of sporadic and NF1-associated neurofibromas, to assess if their presence may indeed be a morphological marker of NF1. Numerous MNFGCs, namely, those that were easily apparent at low magnification (×50 and ×100), were identified only in 5.3% of cases. In 18.1% of cases, a low number of these cells could be observed but only after a careful search, especially at higher magnification (×200 and ×400). Immunohistochemically, all MNFGCs were stained with vimentin and CD34, but not with S-100 protein. Interestingly, there was no statistically significant correlation between MNFGCs (presence or absence) and NF1 (p = 0.73), gender (p = 0.59), age (p = 0.43), and site of tumor (cutaneous vs deep-seated soft tissue; p = 0.27). Our clinicopathologic findings suggest that MNFGCs in an otherwise typical neurofibroma are not a reliable marker of NF1, likely representing a morphological reactive change of the indigenous dermal or endoneurial fibroblasts or dendritic cells in response to unknown microenvironmental stimuli.

Spindle cell/pleomorphic lipoma of the oral cavity.

We herein report a rare case of a lipomatous tumor of the buccal mucosa, showing intermediate morphological features between spindle cell and pleomorphic lipomas, for which the term spindle cell/pleomorphic lipoma is proposed. The presence of multinucleated floretlike cells may pose differential diagnostic problems, especially with spindle cell variant of well-differentiated liposarcoma. Morphological features helpful in the distinction between these tumors are emphasized. Although androgen receptors have been documented in most spindle cell lipomas, suggesting a potential pathogenetic role of sex steroid hormones, no immunoreactivity for androgen, estrogen, and progesterone receptors was obtained in our case. These findings would suggest a different pathogenetic pathway in spindle cell/pleomorphic lipoma of the oral cavity.

Mammary gland: From embryogenesis to adult life.

The aim of this review is to focus on the molecular factors that ensure the optimal development and maintenance of the mammary gland thanks to their integration and coordination. The development of the mammary gland is supported, not only by endocrine signals, but also by regulatory molecules, which are able to integrate signals from the surrounding microenvironment. A major role is certainly played by homeotic genes, but their incorrect expression during the spatiotemporal regulation of proliferative, functional and differentiation cycles of the mammary gland, may result in the onset of neoplastic processes. Attention is directed also to the endocrine aspects and sexual dimorphism of mammary gland development, as well as the role played by ovarian steroids and their receptors in adult life.

Solitary fibrous tumor of the oral cavity with a predominant leiomyomatous-like pattern: A potential diagnostic pitfall

The diagnosis of solitary fibrous tumor (SFT) is usually straightforward if the typical morphologic features, including a wide variety of growth patterns, are identified. We report the clinical, radiologic, and pathologic findings of a rare case of intraoral SFT which exhibited a predominant leiomyomatous-like appearance, closely reminiscent of a leiomyoma, at both incisional and excisional biopsy. Histologically, the tumor was composed predominantly of intersecting fascicles of eosinophilic spindle-shaped cells, variably set in a fibrous stroma. A focal hemangiopericytoma-like growth pattern with alternating hypercellular and hypocellular areas, as well as the deposition of dense keloid-type collagen, raising the suspicion of SFT, could be identified only after a careful examination of the whole tumor. Immunohistochemistry was helpful in confirming the diagnosis of SFT, revealing a diffuse staining of neoplastic cells for vimentin, CD34, bcl-2 protein, and, focally, CD99. Myogenic markers (alpha-smooth muscle actin, desmin, h-caldesmon) were not expressed. The pathologist should be aware of this variant of intraoral leiomyomatous-like SFT to avoid a misdiagnosis of leiomyoma. The distinction of SFT from leiomyoma in the oral cavity is important to assure both correct treatment and prognostic information.

Warthin tumor-like papillary thyroid carcinoma with a minor dedifferentiated component: report of a case with clinicopathologic considerations.

Warthin tumor-like papillary thyroid carcinoma is an uncommon variant of papillary thyroid carcinoma. We report a rare case of Warthin tumor-like variant of papillary thyroid carcinoma with a dedifferentiated component consisting of a solid tumor area composed of neoplastic cells with a spindle to tall cell morphology associated with marked nuclear pleomorphism, atypical mitoses, and foci of necrosis. Although our patient presented with a locally aggressive disease (T3 N1b Mo), she is disease-free without radioiodine therapy after a 23-month follow-up period. We emphasize that Warthin tumor-like papillary thyroid carcinoma, like other morphological variants of papillary carcinoma, may occasionally undergo dedifferentiation. As this component may be only focally detectable, we suggest an extensive sampling of all large-sized (>3 cm) papillary thyroid carcinoma. Recognition of any dedifferentiated component in a Warthin tumor-like papillary thyroid carcinoma should be reported, including its percentage, because it may reflect a more aggressive clinical course.

Atypical epithelioid cell myofibroblastoma of the breast with multinodular growth pattern: A potential pitfall of malignancy

Myofibroblastoma (MFB) of the breast is the prototypical benign spindle cell tumor arising from the mammary stroma. Over the last two decades, several morphological variants of this tumor have been recognized. Epithelioid cell MFB is composed predominantly of neoplastic elements with epithelioid morphology. It represents a potential diagnostic pitfall of malignancy, especially when evaluating small biopsies. We report a unique case of a mammary epithelioid cell MFB composed of large mono- to multi-nucleated cells showing mild to moderate nuclear pleomorphism, predominantly arranged in a multinodular growth pattern. This tumor needs to be distinguished from invasive apocrine, oncocytic, pleomorphic lobular carcinoma, as well as metastases. Immunohistochemistry revealed the fibroblastic/myofibroblatic (positivity for vimentin, desmin, CD34 and focally for α-smooth muscle actin) nature of proliferating cells, and therefore was crucial for a correct diagnosis.

Solitary cutaneous histiocytosis with granular cell changes: a morphological variant of reticulohistiocytoma?

We first report a case of granular cell histiocytosis occurring as a solitary polypoid lesion of the nipple in a 15‐year‐old girl. Histologically, the lesion was composed of a dermal population of medium‐ to large‐sized, short spindle‐ to round‐ to epithelioid‐shaped cells with eosinophilic cytoplasm containing numerous and small diastase‐resistant periodic acid‐Schiff (PAS) positive granules. No associated inflammatory cells were observed. Immunohistochemical studies, revealing immunoreactivity exclusively to vimentin and CD68, were consistent with their histiocytic profile. Based on clinical, morphological and immunohistochemical features, the diagnosis of ‘solitary cutaneous histiocytosis with granular cell changes’ was proposed.

Evaluation of Neoadjuvant Chemotherapy Effects on Liver Parenchyma in Resected Pediatric Malignancies

Neoadjuvant chemotherapy for colorectal liver metastases in adults is responsible for chemotherapy-associated liver injury (CALI), characterized by steatosis, steatohepatitis, and sinusoidal obstruction syndrome. These alterations cause delayed operation to reduce the risk of hemorrhage, portal hypertension, and hepatic failure. Children with hepatic malignancies usually receive neoadjuvant chemotherapy prior to surgery. The aim of this study was to evaluate retrospectively whether the CALI occurs in this pediatric population. This study evaluated patients referred since 1996 for hepatic malignancies who received hepatectomy after chemotherapy. Liver resection material was reviewed, in order to investigate the presence of morphological changes compatible with the CALI in the peritumoral hepatic tissue. Twelve patients were recruited. All patients satisfied the inclusion criteria except one who did not receive neoadjuvant chemotherapy. Eleven children underwent surgery 1 month after the last chemotherapy cycle. All are alive disease-free. Histological examination of specimen revealed only mild changes such as diffuse swelling of hepatocytes and focal, mild portal inflammation. Severe hepatic changes such as steatosis, necrosis, or fibrosis were not identified. CALI-related morphological changes were not found in our patients. The absence of the CALI could be attributed to the younger age of patients (possible different response to stress) and/or to the different chemotherapy schedules compared to those in use for adults patients.