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CD10 is a cell surface metalloproteinase widely expressed in various normal tissue and in epithelial, stromal or both components of various malignancies. The aim of our study was to investigate, for the first time, the expression of CD10 in a series of 135 cases of testicular germ cell tumours in order to asses its possible diagnostic and biologic significance. The expression of CD10 was studied, using immunohistochemistry, in 96 pure forms and 39 mixed forms of germinal cell tumours of the testis. Immunostaining for CD10 was positive in 68/74 (92%) seminomas and 16/24 (67%) seminomatous component of mixed germ cell tumours. The intratubular germ cell neoplasia of the unclassified type always expressed CD10. Anaplastic seminomas, embryonal carcinomas, teratoma and spermatocytic seminomas were negative for CD10. Our findings indicate that only seminomas and intratubular germ cell neoplasia, the precursors of germ cell tumours, express CD10, but when they differentiate along embryonal, somatic, trophoblastic, yolk sac lines they lose CD10 expression. CD10 could be considered a useful marker to differentiate seminoma from other forms of testicular germ cell tumours and for a better estimation of the seminomatous component in mixed germ cell tumours.

Juvenile papillomatosis of the breast ("Swiss cheese disease'') is a benign localized proliferative condition of the breast which occurs almost exclusively in young adult women. Patients with this lesion often have a family history of breast carcinoma, but rarely carcinoma may coexist with the lesion at the time of diagnosis. We present a case of a young male with juvenile papillomatosis of the breast. The pathology and clinical management of this rare lesion is discussed.

Mammary carcinoma arising in ectopic breast tissue is an uncommon occurrence. Most reported cases have involved ductal carcinoma, but other types, such as medullary, papillary, and lobular carcinomas, have been described. For pathologists, the diagnosis of mammary carcinoma arising in ectopic breast tissue can be difficult, especially in the axilla, where carcinoma of adnexal origin must be excluded. We describe a 51-year-old woman who developed invasive secretory ductal carcinoma in ectopic left axillary breast tissue and micrometastatic carcinoma in an ipsilateral axillary lymph node. The carcinoma arose in a left axillary mass that had been present for several years, from which she had secreted fluid during prior menstrual periods.

We evaluated local recurrence, toxicity rate and cosmetic outcome in 72 patients treated with high-dose-rate (HDR) brachytherapy after breast conserving surgery. HDR brachytherapy was administered: i) as partial breast irradiation (PBI) in 64 patients with low-risk early stage breast cancer, enrolled in a phase II prospective study; ii) as PBI after a second conservative surgery as treatment of local relapse in 3 patients; iii) for delivering a boost after whole breast external beam radiotherapy in 5 patients. Implantation was done during surgery (breast conserving or re-excision to achieve adequate surgical margins), with the wound open, or postoperatively. The implant was well tolerated in all patients, so no premature catheter removal was required. At a median follow-up of 32 months (range 5-52) no local recurrence has been observed. Toxicity was very low. Cosmetic outcome was excellent/good in a high percentage of patients. Our results suggest that PBI administered with HDR brachytherapy is feasible in selected patients with low risk early stage breast carcinoma. PBI seems feasible to repeat radiotherapy after a salvage breast conserving surgery for local relapse in a second attempt to preserve the breast.

Melanocytic matricoma is a rare recently described lesion. It usually presents as a pigmented, dark-papular, crusted lesion on sun-damaged skin of adult patients. Histopathologically, these lesions are characterized by well-circumscribed nodules composed of matrical and supramatrical cells with clustered shadow cells, and admixed pigmented dendritic melanocytes. It differs from matricomas and pilomatricomas by its lack of calcification, cyst formation, granulomas, and connections to the epidermis and other adnexal structures. The clinical differential diagnosis includes hemangioma, pigmented basal cell carcinoma, and melanoma. Melanocytic matricoma presumably is the representation of an epithelial-melanocytic interaction in the anagen phase of the hair cycle. An extensive search of the medical literature revealed 11 reports of benign melanocytic matricomas and 5 malignant counterparts. We report an additional case of melanocytic matricoma with discussion of clinicopathologic features and differential diagnosis.

Granular cell tumor (GCT) is a relatively rare neoplasm, usually located in the upper aerodigestive tract, skin and soft tissue. Because of its uncertain histogenesis, GCT has been the object of many immunohistochemical and ultrastructural studies that have suggested a Schwann cell origin. Our recent observation of a case of GCT immunoreactive for Galectin-3 and HBME-1 led us to further investigate the immunohistochemical profile of these neoplasms. We evaluated the immunohistochemical expression of the traditional markers for GCT (S-100, CD68) along with new markers (Galectin-3, HBME-1, Calretinina and Inhibin-alpha) in 22 granular cell tumors. Our results showed, in all cases, a constant diffuse positivity for S-100 protein, CD68 and Galectin-3. HBME-1 was positive in 95% of cases. The present study gives a new immunophenotypic profile for GCT, which could help pathologists in distinguishing morphologically ambiguous granular lesions in unusual sites.

Background: The overexpression of the protein products of genes associated with the cell cycle tumour protein53 (p53), cyclin-dependent kinase inhibitor 2A (p16) and antigen identified by monoclonal antibody Ki-67 (Ki-67) is apparently of great significance. This study evaluated the immunohistochemical expression of these proteins in precancerous lesions and in carcinoma of the oral cavity., Materials and Methods: The nuclear expression of p53 and Ki-67 and nuclear and/or cytoplasmic expression of p16 protein was examined in 54 biopsy specimens from the oral cavity obtained over a period of 3 years. The samples included 18 cases of normal/hyperplastic mucosa, 25 cases of dysplasia and 11 cases of invasive squamous cell carcinoma. The specimens were grouped into three categories: 1 = no or mild dysplasia, 2 = moderate or severe dysplasia, and 3 = invasive carcinoma., Results: p16 was negative in all the group 1 specimens, while both p53 and Ki-67, when present, were limited to the cells of the basal layer. In the group 2 specimens, the number of p16-, p53-, and Ki-67-positive cells increased as the grade of dysplasia progressed. In group 3 (invasive carcinomas), p53 and p16 expression occurred respectively in 81.8% and 54.5% of cases, while Ki-67 was elevated in all the cases., Conclusion: The expression of the cell-cycle proteins p16 and p53 in the dysplastic epithelium, in association with Ki-67, may represent significant markers to recognize evolution of precancerous disease in the oral cavity and to improve identification of the degree of dysplasia.

Objectives: Over-expression of the proto-oncogene c-erbB-2 (HER-2/neu) has been shown to be a prognostic marker in many kinds of cancer, whereas conflicting data exist about the prevalence of HER-2/neu over-expression in squamous cell carcinoma (SCC) of the tongue. The status of Her-2/neu was evaluated in a series of SCC of the tongue to verify the frequency of over-expression of HER-2/neu and evaluate the correlation with traditional diagnostic parameters of this neoplasm., Method: Fourty patients with SCC of the tongue were investigated for over-expression of the protein through immunohistochemistry using CB11 antibody, the Hercep Test kit and FISH., Results: Data obtained using the Hercep Test differ from published reports concerning the over-expression of Her-2/neu and there was no correlation between levels of expression of Her-2/neu and other clinico-pathological and/or prognostic parameters. Of the 40 specimens, using CB11 we obtained results in line with published reports; however, with the Hercep Test we found only 1 positive case (2.5%) (score 3+)., Conclusion: These data, confirmed by FISH, suggest that Her-2/neu is not a suitable marker that could play a primary role in the clinical-therapeutic management of SCC of the tongue.

Basal cell carcinoma with matrical differentiation is an extremely rare variant. To date, only 12 cases have been described in the literature. This tumor is a typical basal cell carcinoma with basaloid nests containing shadow cells identical to those of pilomatricoma and pilomatrical carcinoma. We present two additional cases and have investigated the immunoprofile of .-catenin and osteopontin with the aim of determining both their biological significance and possible diagnostic utility. The morphological and immunohistochemical features of these cases that we have found suggest that basal cell carcinomas with matrical differentiation belong to a spectrum of lesions deriving from hair follicles in which .-catenin plays an important role in the tumor development, differentiation, and behavior.

Small integrin-binding ligand N-linked glycoproteins (SIBLINGs) constitute a family of extracellular matrix proteins involved in bone homeostasis. Their pattern of expression has been primarily reported in bone and tooth and, more recently, in several cancer types. Dentin matrix protein 1 (DMP1), a SIBLING family member, expression was investigated by immunohistochemistry in a retrospective series of 148 primary human breast cancers. Correlations between DMP1 expression levels in the tumors and clinicopathologic features, bone metastases development and relapse of the disease were examined. DMP1 was expressed by 63.5% of the breast tumors analyzed. Significant inverse associations were found between DMP1 expression levels and the size and grade of the tumors (both, P < 0.0001). High DMP1 expression levels in the primary breast lesions were associated with a lower risk of subsequent development of skeletal metastases (P = 0.009). Patients with tumors expressing high levels of DMP1 had a significantly higher disease-free survival rate than those with low DMP1-expressing tumors (P = 0.0062). When DMP1 expression was examined in breast cancer cell lines, we found that non invasive MCF-7 and T47-D cells expressed higher levels than highly invasive MDA-MB-231 and Hs578T cells. Moreover, the specific inhibition of DMP1 expression in MCF-7 cells using siRNAs promoted significantly their migratory capability. Our data implicate for the first time DMP1 expression in breast cancer progression and bone metastases development.

Mesenchymal chondrosarcoma (MCS) is a rare malignant neoplasm of bone or soft tissue origin, locally aggressive, rare in the oral cavity, of which fewer than 100 cases have been reported in the English literature. This is the first case described of this type of tumor affecting the coronoid process. The report describes a unique case of MCS in a 64-year-old woman who presented with swelling and pain at the left preauricular area just anterior to the left tragus. An orthopantomograph showed a large mass in the temporomandibular joint involving the left coronoid process and extending to the left ramus of the mandible. Biopsy and histopathologic examination revealed a biphasic pattern, composed of an undifferentiated small round-cell component surrounding a myxoid of malignant cartilage; a focally pericytic vascular pattern resembling hemangiopericytoma was observed. Immunohistochemical studies were positive for CD99, S-100, and CD45 and negative for desmin, actin, chromogranin, epithelial membrane antigen (EMA), and cytokeratin. The tumor was treated by extensive hemimandibulectomy followed by reconstruction of the area. There was no evidence of disease at the 8-year follow-up. Previously reported cases are reviewed as well.

Background: The assessment of HER-2/neu status is a prerequisite in the clinical management of patients with breast cancer in order to obtain prognostic and predictive information, including Herceptin sensitivity. Immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) are the techniques recommended to detect HER-2/neu alterations and considerable attention is currently being focused on the standardization of these techniques. Intrinsic limitations of IHC, such as antigen preservation and antibody specificity, may make it difficult to score the membrane staining thereby resulting in inconclusive results., Patients and Methods: In this study, 65 invasive breast carcinomas, with doubtful IHC results using the monoclonal antibody CB11, were reanalyzed with two recently licensed assays, the Hercep Test (IHC) and the Path Vision (FISH)., Results: IHC with Hercep Test detected HER-2 protein overexpression in 72% of cases, including nine (14%) strongly positive (3+), 13 (20%) medium positive (2+) and 25 (38%) weakly positive (1+) specimens. FISH testing, with interpretable results in 48 cases, showed a moderate HER-2 gene amplification in only 22% of carcinomas with 2+ or 3+ overexpression., Conclusion: These data indicated an excessive sensitivity of the Hercep Test and suggested that, in the case of indeterminate results after standard IHC, the FISH technique is the best approach to establish HER-2 status.

Data regarding the biologic behavior and surgical management, in particular the axillary lymph node excision, of ductal carcinoma in situ with microinvasion (DCIS-MI) are controversial. Therefore, we decided to study the histopathologic characteristics, the biopathologic profile, as well as the follow-up of a group of patients with DCIS-MI. Thirty-one cases of DCIS-MI, 21 of whom were treated with axillary lymph node dissection, were studied. All cases were classified according to the Van Nuys classification, and the extension of DCIS was quantified. The biopathologic profile (ER, PR, MIB 1, p53, c-erbB-2) as well as the follow-up was also investigated. The results did not reveal any statistically significant differences between the two groups, and there was no statistically significant relationship between the extension of DCIS and the number of microinvasion (MI) foci or maximum MI diameter, or between Van Nuys classification of DCIS and again the number of MI foci or maximum MI diameter. DCIS-MI seems associated with good prognosis. None of the patients had relapses or metastases. Our data seem to suggest that the natural history of DCIS-MI resembles DCIS, and we, therefore, suggest that all the surgically removed area should be examined histologically to avoid missing foci of infiltrating breast cancer larger than 1mm.

Angiomyolipoma is a lesion usually observed in the kidney of patients with tuberous sclerosis. Extrarenal sites are very unusual with sporadic cases in internal organ, soft tissue and skin (fifteen cases have been described in this site). Herein we describe an adding case located on the ear in 58-year-old man reviewing the pertinent literature. The main diagnostic differential criteria are also discussed.

Background: Gefitinib is a selective inhibitor of the epidermal growth factor (EGFR) tyrosine kinase, which is overexpressed in many cancers, including non-small-cell lung cancer (NSCLC). We carried out a clinical study to compare the relationship between EGFR gene copy number, EGFR protein expression, EGFR mutations, and Akt activation status as predictive markers for gefitinib therapy in advanced NSCLC., Methods: Tumors from 102 NSCLC patients treated daily with 250 mg of gefitinib were evaluated for EGFR status by fluorescence in situ hybridization (FISH), DNA sequencing, and immunohistochemistry and for Akt activation status (phospho-Akt [P-Akt]) by immunohistochemistry. Time to progression, overall survival, and 95% confidence intervals (CIs) were calculated and evaluated by the Kaplan-Meier method; groups were compared using the log-rank test. Risk factors associated with survival were evaluated using Cox proportional hazards regression modeling and multivariable analysis. All statistical tests were two-sided., Results: Amplification or high polysomy of the EGFR gene (seen in 33 of 102 patients) and high protein expression (seen in 58 of 98 patients) were statistically significantly associated with better response (36% versus 3%, mean difference = 34%, 95% CI = 16.6 to 50.3; P<.001), disease control rate (67% versus 26%, mean difference = 40.6%, 95% CI = 21.5 to 59.7; P<.001), time to progression (9.0 versus 2.5 months, mean difference = 6.5 months, 95% CI = 2.8 to 10.3; P<.001), and survival (18.7 versus 7.0 months, mean difference = 11.7 months, 95% CI = 2.1 to 21.4; P = .03). EGFR mutations (seen in 15 of 89 patients) were also statistically significantly related to response and time to progression, but the association with survival was not statistically significant, and 40% of the patients with mutation had progressive disease. In multivariable analysis, only high EGFR gene copy number remained statistically significantly associated with better survival (hazard ratio = 0.44, 95% CI = 0.23 to 0.82). Independent of EGFR assessment method, EGFR+/P-Akt+ patients had a statistically significantly better outcome than EGFR-, P-Akt-, or EGFR+/P-Akt- patients., Conclusions: High EGFR gene copy number identified by FISH may be an effective molecular predictor for gefitinib efficacy in advanced NSCLC.

It still needs to be verified whether multiple syncronous homolateral and bilateral breast cancers represent intramammary spread of a single tumor or two or more separate neoplastic events. To clarify this problem, we studied the biopathological profile of 46 homolateral and 20 bilateral cases. The cancers were always surgically removed and processed at the same time. The expression of estrogen receptors (ER), progesterone receptors (PR), MIB 1, p53, and c-erbB-2 was determined. Computer-assisted image analysis (CAS 200) was used to evaluate ER, PR, MIB 1, and p53. The histological concordance was 95.6% in homolateral and 50% in bilateral cases. The immunophenotype profile of multiple homolateral neoplasms showed a concordance between 93.47% for ER and 78.26% for p53. The results were statistically significant for all parameters except for p53. In bilateral cancers, there was a significant statistical concordance for ER. These data strongly suggest that both mechanisms may exert an influence and, in particular, that in the majority of homolateral carcinomas, there may be intramammary spread of tumor cells. In multiple bilateral tumors, however, the great diversity of the histological aspects and the differences in the immunophenotype pattern suggest that the vast majority of these may constitute independent multiple events.

Primary angiosarcomas of the adrenal gland are extremely rare neoplasms, first described in 1988. We report the twentieth case, incidentally discovered in a 60 year-old male. The main histological features were epithelioid appearance and immunohistochemical co-expression of endothelial markers and cytokeratin by neoplastic cells. The potential diagnostic pitfalls of these morphological characteristics are discussed. The patient underwent surgery and adjuvant chemotherapy and is free of tumour recurrence three years after surgery.

Sentinel node biopsy, in the treatment of stage I and II skin melanomas (according to the American Joint Cancer Committee classification), has been advocated by several authors as the best compromise between radical intent and minimal surgical invasiveness. The authors present their personal experience based on 64 sentinel node biopsies in patients with stage I and II skin melanoma of the trunk and limbs (30 males and 34 females; age range: 29-77 years). Sentinel node detection was radio-guided and was conducted in the armpit in 43 cases and in the groin in the remaining 21. Eleven patients who presented metastatic nodes underwent a regional lymphadenectomy (8 axillary and 3 groin dissections) with low morbidity and no perioperative mortality.

Primary synovial chondromatosis is a rare condition characterized by the formation of hyaline cartilaginous nodules; pathogenesis is not fully understood. A soft tissue mass is an even more rare presentation of synovial chondromatosis. Histologically the condition shows some atypical features that suggest a malignant process. We describe a case of primary synovial chondromatosis presenting as soft tissue mass.

Objective: To study the effects of up to 60 days intermittent octreotide on regeneration of rat pancreas stimulated by cholecystokinin after 70% distal resection. DESIGN. Random controlled experimental study., Setting: University hospital, Italy., Materials: 60 Male Wistar rats., Interventions: Distal resection of splenic and gastric lobes of pancreas (70% of whole gland). Rats were allocated to three groups (n = 20 in each): group A (control) were given saline solution 0.5 ml; group B were given cholecystokinin 300 ng/kg; and group C were given cholecystokinin 300 ng/kg and octreotide 2.5 micrograms/kg. All substances were injected subcutaneously twice a day until death. Four rats were killed weekly for four weeks, and the remainder at 60 days., Main Outcome Measures: Increase in weight of the gland as a percentage of the weight of the whole gland, and DNA synthesis measured by bromodeoxyuridine (BrdU) nuclear labelling index., Results: In the cholecystokinin alone group pancreatic weight had increased significantly on days 21 and 28 (95% confidence intervals (CI) - 13.8 to 12.2 and -44.1 to 19.7, respectively) and the BrdU index had increased significantly at 21 (0.56 to 0.80), 28 (0.26 to 1.3), and 60 (0.09 to 0.51) days compared with the control group. In the group given both cholecystokinin and octreotide the weight was significantly lower than in the cholecystokinin alone group at 21 and 28 days (95% CI - 1.02 to 66.7 and 3.5 to 34.7, respectively) and the BrdU index was significantly lower at 28 days (0.40 to 1.19)., Conclusions: Octreotide seems to reduce the pancreatic regeneration induced by cholecystokinin in rats after 70% distal resection. To our knowledge this has not previously been shown, and the mechanism must be elucidated further.

This paper reports a case of giant cell reparative granuloma of the right maxillary bone of a 13-year-old caucasian girl. It may be very difficult to distinguish this entity from other lesions of mandible, maxilla and skull bones which contain multinucleated giant cells. The differential diagnosis, especially from giant cell tumors of the bone, is discussed. Accurate diagnosis lies on correct integration of clinical, radiographical and histopathological data.

Opportunistic infections with Strongyloides stercoralis are rare in Western countries. However, individuals with cellular immunity defects may develop a disseminated infection. We report the case of a 78-year-old Italian male who developed progressive respiratory failure six weeks after initiation of corticosteroid therapy for temporal arteritis. Infective filariform Strongyloides stercoralis larvae, found in the sputum one day before death, clarified the complex clinical picture. It is advisable that before and during immunosuppressive treatments, the stools and body fluids of patients should be screened for parasites.

Primary malignant melanomas of the nasal cavity are rare, as only 400 cases have been reported to date. The present paper describes two cases recently seen in Caucasian women. The authors point out the difficult clinical diagnosis, as the symptoms are rather aspecific. From the histopathological point of view, diagnosis is easy in the melanotic cases while can show interpretating problems in the amelanotic ones, when melanoma is almost indistinguishable from other malignant neoplasms. A correlation between histological grading and prognosis was not detected, as both cases showed local recurrences within one year after surgery although they were, respectively, of epithelioid and undifferentiated type. While surgery appears to be the choice treatment of the primary lesion, the treatment of cervical metastasis is still disputable. On the whole, most authors think that the role played by radio- and mainly chemo-therapy is still limited and that cervical adenopathies should be treated by a simple lympho-adenectomy rather than by a neck dissection.