Atypical thyroid nodules express both HBME-1 and Galectin-3, two phenotypic markers of papillary thyroid carcinoma.

Ninety-six thyroid lesions were immunohistochemically evaluated for HBME-1 and Galectin-3 expression including nodules with cytological atypia, the latter defined as nuclear features suggestive but not diagnostic of papillary thyroid carcinoma. Thirty nodules with cytological atypia, 49 papillary thyroid carcinomas (PTCs), 4 follicular carcinomas and 13 oxyphilic tumors were examined. Forty-one of the 49 PTCs, 16 atypical thyroid nodules and 3 non-malignant oxyphilic tumors exhibited a combined expression of HBME-1 and Galectin-3. In 6 of the sixteen atypical thyroid nodules the immunoreactivity for both markers was strong and diffuse, simulating the pattern observed in PTC. We conclude that thyroid nodules with cytological atypia and strong/diffuse positivity for both HBME-1 and Galectin-3, two well recognized markers of PTC, represent a starting phenotypic change towards PTC, for which a benign or borderline counterpart has not yet been defined. The expression of HBME-1 and Galectin-3 in some thyroid nodules is related to the presence of cytological atypia suggestive but not diagnostic of PTC. The phenotypic similarity between this subset of thyroid nodules with cytological atypia and PTC is also confirmed by our data according to which Galectin-3 and HBME-1 have been found to be highly sensitive for PTC.

Pulmonary artery sarcoma: an insidious tumor still diagnosed too late. Analysis of the literature and report of a case.

Pulmonary artery sarcoma is an exceptionally rare tumor which must be considered in the differential diagnosis of pulmonary thromboembolism. We report the case of a 36-year-old woman and review 100 cases published in the literature between 1988 and 2005. The patient presented with a history of dyspnea, fatigue, fever, night sweats and anemia that did not respond to antibiotic therapy. She also had hemoptysis. Transvenous catheter biopsy was indicative of sarcoma. A left pneumonectomy was performed, followed by five cycles of chemotherapy. Histological and immunohistochemical studies documented an intimal sarcoma with myofibroblastic differentiation. The patient is alive and well 20 months after surgery. The clinico-pathological features of pulmonary artery sarcoma are described.

Myxoid monophasic synovial sarcoma: case report of an unusual histological variant.

We report the case of a 61-year-old woman who presented a recurrent myxoid synovial sarcoma involving the right ankle and foot. This tumor, defined as a synovial sarcoma showing more than 50% myxoid change in the stroma, has only recently been described as a rare histological variant. The histological diagnosis is particularly difficult in such cases, as the one we are describing, where the tumor is entirely myxoid and monophasic raising the possibility of other myxoid soft tissue neoplasms, such as extraskeletal myxoid chondrosarcoma, malignant peripheral nerve sheath tumor or leiomyosarcoma. On the basis of morphological and immunophenotypical findings, the diagnosis of myxoid synovial sarcoma should be properly established, especially in view of its unusual clinical course and treatment. Furthermore, we will discuss the clinicopathological and immunohistochemical features observed in our case.

Primary small cell neuroendocrine carcinoma of the breast.

We report and characterize immunohistochemically a case of primary small cell neuroendocrine carcinoma of the breast. The tumor, which arose in the left side, was 18 cm in maximum diameter and microscopically was composed of patternless sheets of undifferentiated small cells with a high nuclear-to-cytoplasmic ratio, hyperchromatic nuclei with indistinct cytoplasm, inconspicuous nucleoli, numerous mitotic figures and large areas of coagulative necrosis. Tumor cells were positive for bcl-2, neuron-specific enolase, synaptophysin, CAM 5.2 and cytokeratin AE1/3, but negative for LCA, CD30, HMB-45, chromogranin A, estrogen receptor, progesterone receptor, Her-2/neu and CD99. The opposite breast harboured an intraductal carcinoma with a focus suggesting microinfiltration, a finding never reported before. In this paper we have also extensively reviewed the literature on the subject, emphasizing the variable immunohistochemical profile and the aggressiveness of mammary small cell carcinoma. The rapidly fatal clinical course of our case, which appears to have the largest dimensions described in literature, underlines the importance of an early diagnosis and treatment for long-term survival.

[An atypical bone metastasis of hepatocellular carcinoma: case report and review of the literature]. / Una metastasi ossea atipica in corso di epatocarcinoma: descrizione del caso clinico ed analisi della letteratura.

Bone metastases are a quite frequent complication of hepatocellular carcinoma (HCC). They are a substantial fraction (about 14-28%) of the metastatic locations of this neoplasm. Recent studies are indicative of the clinical usefulness of local therapy of HCC bone metastasis, expecially if they are single locations. The presence of a single bone metastasis does not seem to influence short term prognosis of the primary neoplasm and, furthermore, its treatment by radiation, chemio-embolization or surgery may obtain long-term pain control, without the side effects of analgesic drugs. Most frequently, bone metastases of HCC appear in the spine, femur, humerus or ribs. In the last years, some atypical locations, as jaws, gums and skull, were reported. In this paper, we report the case of a painful bone metastasis of HCC, localized at the second phalanx of the second finger of the right hand. To our knowledge, until now only two cases of HCC metastatic location at the bones of the hand have been reported. The lesion has been treated by surgical ablation, obtaining long-term pain remission and the withdrawal of the analgesic drugs. Few weeks later, another bone metastasis appeared, located at the second phalanx of the third finger of the same hand, indicating in this subject a peculiar "metastatic tropism".

Evaluation of galectin-3 expression by sarcomas, pseudosarcomatous and benign lesions of the soft tissues. Preliminary results of an immunohistochemical study.

Galectin-3 is an endogenous galactose-binding protein that is expressed in several normal and neoplastic tissues and is thought to play a role in a variety of biological processes. In this study we have examined the immunohistochemical expression pattern of galectin-3 in the most representative categories of soft tissue tumors consisting of 162 patients' specimens. Lesions were classified according to histogenetic criteria into 13 major categories. Overall, there were 18 fibrous tumors (13 benign, 4 intermediate and 1 malignant), 21 fibrohistiocytic tumors (5 benign, 11 intermediate and 5 malignant), 22 lipomatous tumors (14 benign and 8 malignant), 20 smooth muscle tumors (12 benign, 5 intermediate and 3 malignant), 2 skeletal muscle tumors (2 malignant), 19 vascular tumors (9 benign and 10 malignant), 6 perivascular tumors (5 benign and 1 malignant), 7 synovial tumors (4 benign and 3 malignant), 3 benign mesothelial tumors, 27 neural tumors (25 benign and 2 malignant), 7 cartilaginous and osseous tumors (4 benign and 3 malignant), 8 miscellaneous tumors and 2 high grade unclassified sarcomas. Galectin-3 was constantly expressed by almost all the major categories of benign, pseudosarcomatous and malignant soft tissue tumors. At this time no data are available in the literature about the expression of galectin-3 distribution in a wide range of soft tissue tumors. In the present work we discuss the significance and the possible usefulness of such findings.

Rare presentation of carcinosarcoma arising in bladder diverticulum.

An 87-year-old man presented with hematuria and dysuria. An endoscopic examination revealed a bladder mucosa which was almost entirely occupied by diverticula. On the left lateral wall of the bladder there was a huge diverticulum which contained a 12 cm mass extending beyond the bladder wall in the extraperitoneal tissues. Upon histological examination the mass proved to be a carcinosarcoma which was composed by a squamous carcinoma and a sarcoma resembling a malignant fibrous histiocytoma. The two components, i.e. carcinomatous and sarcomatous, were separated by a sharp collision border and no intermingling was ever noted. The epithelial component showed immunoreactivity for cytokeratin and EMA, while the mesenchymal component was diffusely reactive for vimentin, alpha-1-antitrypsin and lysozime. Both components were reactive for galectin-3, whereas S100, desmin and smooth muscle actin were negative. This is the fourth reported case of carcinosarcoma originating in a bladder diverticulum.

Papillary carcinoma in amyloid goitre.

Amyloid goitre is a rare lesion characterized by a diffuse and bilateral enlargement of the thyroid gland due to amyloid deposition. It is uncommon that a massive and widespread amount of adipose tissue deposition is found within these lesions and only in exceptional cases a differentiated carcinoma can develop. We describe the third example of thyroid carcinoma, arising in a 74-year old female who had also massive adipose thyroidal metaplasia, within amyloid goitre. The Congo red stain confirmed the diagnosis of amyloid goitre. Immunohistochemistry showed reactivity with MoAb against amyloid fibril protein A. The patient suffered from renal failure of undetermined aetiology for three years, but neither systemic amyloidosis nor risk factors for its development were found. It is important to correctly diagnose amyloid goitre both to rule out the presence of a differentiated thyroidal carcinoma and to search for amyloid infiltration in other organs in view of an early appropriate therapy.

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.

Malignant oncocytoma of major salivary glands. Report of a post-irradiation case.

The fourth case of malignant oncocytoma arising in the submandibular gland is here reported. This tumor arose in a 48-year-old man after radiation exposure, a finding never described before for malignant oncocytoma. In addition, several regional metastatic lymph nodes were found. The diagnosis was confirmed by histochemical and ultrastructural findings. The tumor cells showed easily recognizable mucus production and, ultrastructurally, abundant mitochondria, intracytoplasmic lumina lined by microvilli and lipid droplets. These last features have only seldom been described in malignant oncocytoma. Furthermore, the neoplastic cells were alpha-1-antitrypsin positive and S100, thyroglobulin, carcinoembryonic antigen, and smooth muscle actin negative. A thorough review of the literature is also presented.

Comparative analysis of proliferating cell nuclear antigen and epidermal growth factor receptor expression in glial tumours: correlation with histological grading.

The present study analyzed the combined immunostaining for proliferating cell nuclear antigen (PCNA) and epidermal growth factor receptor (EGFR) with the aim of obtaining an objective method for the evaluation of the growth fraction in human glial tumors. A retrospective study was undertaken on 157 gliomas employing MoAb PC10 and MoAb 108, recognizing a 36 Kd nuclear protein associated with the cell cycle and the extracellular domain of the EGFR, respectively. The results of this immunohistochemical analysis showed that the rate of PCNA positive cell is directly associated to EGFR expression and significantly (P < 0.0001) correlates with tumor morphological grading, this was also the case in patients submitted to multiple surgical treatments for recurrent tumors. PCNA and/or EGFR are expressed by a minority of low grade astrocytoma, while anaplastic astrocytoma and glioblastoma displayed an intense immunoreactivity for the two antigens in more than 85% of tested cases. These findings indicate that the combined evaluation of PCNA and EGFR could allow a more definite biopathological grading of neuroepithelial brain tumours.

Medium-large polyps of the colon: a contribution for their clinical profile and a proper surveillance.

A retrospective analysis of polypoid lesions of the colon larger than 1 cm was performed with the aim to study their characteristics and a proper surveillance schedule. We reviewed all colon polypoid lesions larger than 1 cm found and treated during the period January 1984- December 1993 that were not considered cancer macroscopically. The records of 361 patients with 391 polyps are the object of this report. The polyps were divided into subgroups according to size: A) less than 20 mm, B) between 21 and 30 mm, and C) larger than 30 mm. Out of 391 polypoid lesions 373 were adenomas: 60% were found in males. The age group distribution showed no differences among the subgroups. The pedunculated type showed a decrease from 69.1% to 43.3% with the increasing of size: inverse figures were observed for sessile polyps. The lesions were mainly located in left colon. Synchronous adenomas were found in 25.4% patients, and metachronous and previous adenomas respectively in 24.8% and 5.2%: no significant difference was present in the subgroups. Synchronous malignancy in the colon was found in 2% of the patients. Histological characteristics demonstrated a decrease of tubular adenoma from 46.5% to 22.6% from subgroup A to C, while villous adenomas increased inversely from 6.6% to 15.1%. The presence of severe dysplasia ranged from 20.9% to 56.1% in subgroups A and C, respectively, and adenomas with invasive cancer showed a significant increase from the subgroup A to C, respectively from 4.3% to 10.5%. During an average 36-month follow-up we observed 2 metachronous colon cancers, surgically treated in Dukes stage B, 84 metachronous adenomas, all less than 10 mm and without malignant alterations. Our data confirm other literature reports regarding the profile of colon adenomas with an increasing risk of malignancy with the increase of size and the presence of villous structure. In our opinion the assessment of a "clean colon" status is important when an adenoma is found in the colon. The proper follow-up for adenomas must be tailored for any individual patient when risk factors such as size, villous structure, personal and family history of neoplastic lesions of the colon are present. The follow-up schedule, presently recommended for colon adenomas, must be flexible according to these parameters.

Follicular carcinoma in lingual thyroid presenting as a latero-cervical mass. Case report and review of the literature.

A follicular carcinoma arising in a lingual thyroid and presenting as a submandibular mass is reported. The tumor showed a mixture of solid sheets of follicular cells and well-formed follicles displaying variable levels of cytological atypia. True vascular invasion was confirmed. To the best of our knowledge, this is the first example of carcinoma arising in lingual thyroid that presented as a latero-cervical mass.

Identification of second malignancies on effusions and fine-needle aspirates using a panel of monoclonal antibodies.

The longer survival of neoplastic patients achieved through improvements of therapeutic regimens has increased the relative risk of developing a second primary tumour (SPT). In this context, conventional cytopathology can define tumour histotype only in a small fraction of cases. In this study, we have evaluated whether selected combinations of monoclonal antibodies (MAbs) to tumour-associated antigens (TAAs) can increase the accuracy of conventional morphology in detecting second primary tumours (SPTs) in two particularly difficult areas of cytodiagnosis, namely that of effusions and pulmonary fine-needle aspirates (FNAs). The immunocytochemical (ICC) analysis of 334 cytological specimens demonstrated that the use of our selected panel of MAbs could allow a more efficient identification of SPTs in comparison with conventional morphology. This diagnostic improvement was statistically significant (P < 0.0001). The present findings show that the immunophenotyping of effusions and FNAs, providing a more accurate and objective identification of SPTs, may have significant therapeutic and epidemiological relevance.

Selected monoclonal antibodies can increase the accuracy of cytodiagnosis of neoplastic effusions of cryptic origin expanded in a short term culture.

The use of a selected panel of monoclonal antibodies (MoAb) to tumor associated antigens (TAA) in immunocytochemical (IIC) tests has been shown, in a preliminary study, to be a powerful diagnostic tool for the identification of the primary solid tumor causing metastatic effusion. Despite this improvement in a minority of neoplastic fluids a number of different causes may still determine false negative (FN) immunocytochemical diagnoses. The aim of the present study was to confirm the diagnostic accuracy of this panel of MoAb. This was done by analyzing in IIC tests a larger number of effusions and by evaluating whether the expansion in short term culture of those fluids with an uncertain malignant morphology could provide an adequate cellular substrate for immunocytodiagnosis. The analysis of 314 effusions confirmed the results of the pilot study and demonstrated that the combination of short term culture and immunocytochemical assays can further increase the sensitivity of this novel diagnostic procedure from 84.3% to 95.3%.

Selective location of palisaded myofibroblastoma with amianthoid fibres.

The occurrence of a palisaded myofibroblastoma with amianthoid fibres in the left inguinal lymph node of a 51 year old man prompted an investigation of the factors underlying its exclusive location. The antigen profile was characterised which confirmed the homogeneous expression of vimentin and smooth muscle actin as well as the lack of desmin. Use of monoclonal antibodies to check for a differential distribution of myofibroblasts and the putative cell of origin of palisaded myofibroblastoma showed that inguinal lymph nodes have abundant vimentin and actin positive cells and desmin negative cells. This suggests that the selective occurrence of myofibroblastoma is related to the nodal microenvironment, providing a source of available and potentially proliferating myofibroblasts. Mast cells abounded in this lesion, particularly around amianthoid fibres, as well as in pelvic and inguinal lymph nodes. In view of the known role of mast cells in interstitial matrix degradation it is postulated that the core of amianthoid fibres represents degraded interstitial matrix, analogous to the sclerotic areas commonly found in the above mentioned lymph node groups, while the peripheral spokes, so peculiar to this entity, are the result of vimentin and smooth muscle actin, directly shed by proliferating myofibroblasts.

Potential use of monoclonal antibodies in the diagnostic distinction of gynecomastia from breast carcinoma in men.

Immunohistochemical (IHC) assays using the monoclonal antibodies (MoAbs) B72.3 and B6.2, recognizing two distinct and independently expressed breast tumor-associated antigens (BTAAs), recently have been shown to significantly improve the accuracy of cytodiagnosis of breast nodules by fine-needle aspiration (FNA). To evaluate whether the same method may be useful diagnostically in distinguishing gynecomastia from breast cancer in men, a retrospective avidin-biotin immunoperoxidase assay study was performed on 50 cases of gynecomastia and 30 cases of breast carcinoma in men, using a panel of five MoAbs known to recognize different BTAAs. The results of this study demonstrated that MoAbs B1.1, HMFG2, and MBr1 displayed a strong reactivity with gynecomastia and carcinoma, but MoAbs B72.3 and B6.2 separated benign and malignant lesions in a high percentage of cases. When used in combination, the latter two reagents reacted with 96% of the carcinomas that were analyzed but labeled only 67% of gynecomastia cases. Thus, the conjoint use of these two reagents may enhance the use of FNA biopsy as a valuable tool in the presurgical diagnosis of breast nodules in men.

Gastric syphilis simulating malignant lymphoma.

We report a case of syphilis of the stomach, occurring in a 50 year old man, which simulated malignant lymphoma microscopically and had also the endoscopic appearance of a malignancy. To the best of our knowledge this is the first report of gastric syphilis mimicking a lymphoma, and we believe that the recognition of this presentation is of particular importance to correctly set the disorder especially for therapeutic purposes and in order to avoid unnecessary surgery.