Co-occurrence of a metastatic mammary liposarcoma and an ovarian sex-cord stromal tumor in a dog.

Sarcoma arising in the mammary gland is a rare tumor in dogs, and primary liposarcoma with metastatic behavior has never been previously reported among canine mammary tumors. A 14-year old female poodle had a mammary mass diagnosed as pleomorphic liposarcoma. Two years following surgical removal, the tumor recurred in the mammary gland with lymph node metastases. In addition, a sex-cord stromal tumor was identified in the ovary. Immunohistochemistry was performed on both tumors that were positive for oestrogen and progesterone receptors. Moreover, the ovarian tumor was positive for calretinin. This is the first report to the authors' knowledge, of the co-occurrence of a pleomorphic liposarcoma of the mammary gland and an ovarian sex-cord stromal (gonadostromal) tumor in the dog.

Pulmonary inflammatory pseudotumor due to Coxiella burnetii. Case report and literature review.

A 58-year-old man was admitted because of respiratory failure, episodic fever with chilling, cough, malaise, fatigue, myalgia and weight loss lasting for at least one month. Chest x-rays and CT scan of the chest showed bilateral pulmonary consolidations in upper lobes, the left lower lobe, and mediastinal lymphadenopathy. Bronchoscopy with cytology was unremarkable. A needle CT-guided lung biopsy documented an inflammatory pseudotumor, lymphoplasmacytic type. Serology showed high titer antibodies to phase II Coxiella burnetii infection. Therapy with doxycycline and hydroxychloroquine for three months led to a complete resolution of symptoms and radiological findings, and a marked decrease in titers to Q fever.

P16 immunostaining and HPV testing in histological specimens from the uterine cervix.

BACKGROUND: The cellular tumor suppressor protein pl61NK4a (p16) has been identified as a biomarker for transforming human papilloma virus (HPV) infections. P16 is a cyclin-dependent kinase inhibitor that regulates the cell cycle and cell proliferation by inhibiting cell cycle G1 progression. PURPOSE OF THE STUDY: To confirm the role of p16 as biomarker for transforming HPV infections and possible clinical applications in histological samples from the uterine cervix. MATERIALS AND METHODS: The subject of this study included 56 biopsies of the cervical canal collected from January 2012 to September 2012 in the Institute of Pathology of the University of Sassari. The search for HPV immunohistochemistry was performed with the monoclonal antibody DAKO 1:25, while for the detection of p16 was used CINtecTM p16 (INK4a) histology kit. RESULTS: In 56 biopsies performed in women aged between 23 and 69 years, the authors highlighted, by histological analysis, 24 cases of low-grade squamous intraepithelial lesion (LSIL) - cervical intraepithelial neoplasia (CIN1) and 31 cases of high-grade squamous intraepithelial lesion (HSIL) - CIN2/3); 15 CIN2, 14 CIN3, and two cervical squamous cell carcinoma in situ (SCIS). One case was an infiltrating squamous cell carcinoma (ISC). In 24 CIN1, there was a 16.67% positivity for p16 and an equal percentage occurred for HPV. In 15 cases of CIN2 the percentage of positivity for p16 was considerably increased (73.33%), unlike the search for HPV which had a positivity rate of 20%. Finally, in 14 cases of CIN3, and in three carcinomas, the positivity for p16 was equal to 100%, however the search for HPV positivity was between 0% and 7.14%. CONCLUSIONS: These results demonstrated that p16 was a highly sensitive marker of cervical dysplasia. The authors have shown that p16 overexpression increased with the severity of cytological abnormalities and that had a greater ability to identify the viral infection compared to the classical immunohistochemical staining for HPV.

Immunohistochemical evaluation of epithelial antigen Ber-Ep4 and CD10: new markers for endometriosis?

BACKGROUND: Early and certain diagnoses of endometriosis are mandatory to begin the correct treatment and to exclude the risk of endometriosis-associated ovarian carcinoma (EOC) and endometrial stromal sarcoma (ESS). PURPOSE OF THE STUDY: To assess the immunohistochemical expression of Ber-Ep4, an epithelial antigen, and CD10 in endometriosis. MATERIALS AND METHODS: Forty-eight women underwent laparoscopic surgery for endometriosis and endometriotic samples were recovered for histology. In all surgical specimens Ber-Ep4 and CD10 were searched by an immnohistochemical method. The authors evaluated the correlations among the immunohistochemical positivity and the location of endometriosis. RESULTS: Most cases (40/48 83.34%) were represented by ovarian endometriotic cyst. Among the eight remaining cases, three (3/48, 6.25%) were pelvic endometriotic lesions, two (2/48, 4.17%) peritoneum of vesico-uterine pouch, one vaginal lesion (2.08%), one salpinx lesion (2.08%), and one inguinal location (2.08%). Ber-Ep4 and CD10 were expressed in 90% and in 100% of the ovarian lesions, respectively. In pelvic lesions Ber-Ep4 and CD10 showed both 66.67% of positivity and had the same pattern in peritoneal, salpinx, vaginal, and inguinal lesions (50%, 100%, 100%, 100%, respectively). Ber-Ep4 was negative in 6/48 (12.5%) cases whereas CDO10 was negative in 2/48 (4.17%) cases of endometriosis. The sensitivity of Ber-Ep4 and CD10 for endometriosis diagnosis were 87.50% and 95.83%, respectively. Immunohistochemistry for Ber-Ep4 showed positivity in all cases of endometriosis with typical cubic epithelium, whereas CD10 was positive in 1/2 (50%) atypical case. CONCLUSION: Immunohistochemical expression of Ber-Ep4 and CD10 was positive in most cases of endometriosis and was useful in differential diagnosis with mesothelial cysts. Ber-Ep4 was negative in cases of hyperplastic epithelium or cytological atypia; these cases are not well-differentiated and could be optimally treated by surgery and not by hormonal therapy because of the risk of cancer degeneration.

Immunohistochemical evaluation of a new epithelial antigen, BER-EP4 in ovarian cancer: a propos of 62 cases.

OBJECTIVE: To assess the immunohistochemical expression of BerEP4, a new epithelial antigen in ovarian cancer. METHODS: We studied 62 cases of ovarian cancer in which BerEP4, CEA and CA-125 were investigated by an immunohistochemical method. We evaluated the correlations among immunohistochemical positivity and the grading, histotype and stage of disease. RESULTS: BerEP4 was positive in 45 out of 62 cases (72.58%), CA-125 in 36 out of 62 cases (58.06%) and CEA in ten out of 62 cases (16.13%). BerEP4 was present both in serous and in mucinous tumors (80.96% vs. 80.77%). CA-125 was mainly expressed in serous vs mucinous tumors (66.67% vs. 57.69%). CEA was more prevalent in mucinous vs. serous tumors. Ber-EP4 was mainly expressed in G1 (75%) and G2 (77.27%). CA-125 was more present in G1 and G3 (both 62.50%) than G2 (50%), whereas CEA showed positivity in G1: 12.50%, G2: 22.73% and G3: 12.50%. There were no differences among the three antigens studied with regard to clinical stage. CONCLUSIONS: In our study Ber-EP4 was positive in 45 out of 62 cases (72.58%) of primary epithelial ovarian cancers. The presence of this antigen seemed to be related to the histotype and grading but not to clinical stage.

Analysis of epidermal growth factor receptor (EGFR) status in endometrial stromal sarcoma.

PURPOSE: Endometrial stromal sarcomas (ESSs) are rare neoplasms, which are currently treated by surgery, whereas effective adjuvant therapies have not yet been established. Recently, epidermal growth factor receptor (EGFR) expression has been described in ESS, and a potential role of EGFR-targeted adjuvant therapies has been proposed. The aim of this study was to analyze EGFR status in an ESS series and to evaluate their potential role as molecular targets. MATERIALS AND METHODS: EGFR status was investigated in a total of ten cases of ESS, which included seven low-grade ESS and three undifferentiated ESS cases. EGFR expression levels were assessed by immunohistochemistry, and gene amplification analysis was performed with dual-color fluorescence in situ hybridization (FISH). RESULTS: Nine out of ten ESS cases showed positive immunostaining, whereas FISH analysis demonstrated constantly negative results. CONCLUSIONS: This study confirmed that EGFR is frequently overexpressed in ESS. FISH analysis did not show EGFR amplification in any of the tumors, therefore EGFR expression in ESS should be related to different genetic mechanisms.

[Occupational and environmental cancer in southern Sardinia: a survey on ten years of hospitalizations]. / Tumori ad elevata frazione eziologica occupazionale o ambientale nella ASL di Cagliari: un' analisi di 10 anni di ricoveri.

Based on hospital discharges in 1001-2010, we calculated risk of tumours with an elevated occupational and environmental etiological fraction by health district of residence within the Local Health Unit (LHU) N. 8 of Sardinia. With reference to the age and gender-specific hospitalization rates of the whole LHU, residents in the urban Cagliari health district showed an excess risk of haemolymphopoietic cancer (RR = 1.07; 95% CI 1.03-1.12) and bladder cancer (RR = 1.10; 95% CI 1.05-1.16); in both instances, risks were higher among female residents. The highest excess risk for lung cancer was observed among residents in the Quartu-Parteolla health district (RR = 1.13; 95% CI 1.05-1.21), and it was slightly higher among male residents. The results appear to confirm the role of urban factors in increasing cancer risk.

Mammography and ultrasound imaging of preinvasive and invasive canine spontaneous mammary cancer and their similarities to human breast cancer.

Understanding the evolution of proliferative breast disease such as atypical hyperplasia and carcinoma in situ is essential for clinical management of women diagnosed with these lesions. Therefore, an animal model that faithfully represents human breast disease in every aspect from spontaneity of dysplasia onset, histopathologic features, and genetics to clinical outcome is needed. Previously, we studied canine spontaneous atypical hyperplasia and ductal carcinoma in situ (low, intermediate, and high grade) and reported their similarities to human lesions in histopathologic and molecular features as well as prevalence. To further validate the resemblance of these lesions to humans, we examined their mammographic and sonographic characteristics in comparison with those of human's as well as the potential of the human Breast Imaging Reporting and Data System (BI-RADS) to predict canine disease. Nonlesional, benign, and malignant mammary glands of dogs presented to Sassari Veterinary Hospital were imaged using mammography and ultrasonography. The images where then analyzed and statistically correlated with histopathologic findings and to their similarities to humans. Our results showed that canine mammary preinvasive lesions, benign, and malignant tumors have mammographic abnormalities, including the presence, pattern, and distribution of macrocalcification and microcalcification, similar to their human counterparts. BI-RADS categorization is an accurate predictor of mammary malignancy in canine, with 90% sensitivity and 82.8% specificity. The similarities of mammographic images and the ability of BI-RADS to predict canine mammary malignances with high specificity and sensitivity further confirm and strengthen the value of dog as a model to study human breast premalignancies for the development of prognostic biomarkers.

The effect of puberty on insulin resistance in obese children.

OBJECTIVE: Insulin resistance (IR) increases during puberty in normal children. IR is the first adverse metabolic event of obesity, and the marker of the metabolic syndrome. We aimed to study the effect of puberty on IR in obese and normal-weight children. DESIGN: Cross-sectional evaluation of fasting glucose, insulin concentrations, and homeostasis model assessment of IR (HOMA-IR) in obese and control children throughout puberty. PATIENTS AND METHODS: We recruited 424 obese children (207 pre-pubertal and 217 pubertal divided in Tanner stages 2-3, 4, and 5) and estimated IR using the HOMA-IR index. Data were compared to those obtained in 123 healthy normal-weight children (40 pre-pubertal and 83 pubertal divided in Tanner stages 2-3, 4, and 5). RESULTS: In the obese children mean HOMA-IR increased progressively across Tanner stages, and was significantly higher in all groups (pre-pubertal and Tanner stages 2-3, 4, and 5) of obese than in control children. HOMA-IR was significantly correlated with BMI. CONCLUSIONS: HOMA-IR in obese children increases at puberty more than in normal-weight children and does not return to pre-pubertal values at the end of puberty.

Receptor modifications in vulvar dystrophies before and after treatment with topical hormones: comparison between the dextran-charcoal technique and immunohistochemical evaluation.

PURPOSE OF INVESTIGATION: The objective of the study was first to quantify estrogen receptors (ERs) and progesterone receptors (PRs) in dystrophic vulvar tissue before and after topical hormone treatment in an attempt to evaluate whether receptor modifications occurred. Second we compared quantitative analysis with immunohistochemical staining of the vulvar specimens. METHODS: We studied 115 vulvar specimens obtained from 75 consenting women ranging from 21 to 78 years of age. Of the patients, 12 had histologically normal vulvar skin, 45 had vulvar dystrophies that were not treated by topical steroid therapy, 28 patients had vulvar dystrophies that were treated by testosterone propionate (TP) 2%, 12 patients had vulvar dystrophies that were treated by progesterone in hydroalcoholic gel and 18 patients had vulvar malignant tumors. For immunohistochemical analysis we considered 25 cases of vulvar dystrophies: 11 cases of squamous hyperplasia (SH) and 14 cases of lichen sclerosus (LS). Among these 25 cases, 15 (5 SH and 10 LS) were treated with TP 2%. RESULTS: After treatment of the vulvar dystrophies with progesterone, the positivity of ERs decreased (58.3% vs 77.8%). After treatment of the vulvar dystrophies with TP 2%, the positivity of PRs significantly decreased (14.3% vs 68.9%) whereas after treatment with progesterone the positivity of PRs increased (83.3%). The immunohistochemical study showed some differences in comparison to the quantitative study. In fact we found low basal positivity especially for PRs (16% vs 68.9% of the quantitative study). This finding was due to the use of a cutoff of at least ++ in order to increase the specificity. After treatment with TP 2%, we observed an increase of immunohistochemical positivity for ERs even in cases that were negative before treatment and a lack of PRs even in cases that were positive before treatment. CONCLUSIONS: These data demonstrate the efficacy of androgen therapy with TP 2% in vulvar dystrophies with increased trophism due to the increase of ERs.

Development of multifocal squamous cell carcinoma in lichen sclerosus et atrophicus of the penis associated to HCV hepatitis.

We describe the case of a 59-year-old uncircumcised man, with a history of meatal stenosis and balanitis xerotica obliterans (lichen sclerosus et atrophicus) and human C virus hepatitis, who developed an infiltrating squamous cell carcinoma of the penis. The relationship among these conditions is discussed.

Immunohistochemical evaluation of a new epithelial antigen, Ber-EP4, in ovarian cancer: preliminary results.

OBJECTIVE: To assess the immunohistochemical expression of Ber-EP4, a new epithelial antigen in ovarian cancer. METHODS: We studied 25 cases of ovarian cancer in which Ber-EP4, CEA and CA 125 were investigated by an immunohistochemical method. We evaluated the correlations between immunohistochemical positivity and grading, histotype and stage of disease. RESULTS: CEA was positive in 5 out of 25 cases (20%), CA-125 in 17 out of 25 cases (68%) and Ber-EP4 in 14 out of 25 cases (56%). Ber-EP4 was mainly present in mucinous tumors in comparison to serous tumors (78.6% vs. 50%). Ber-EP4, as well as CA-125, were directly proportional to tumor differentation (70% of positivity in G1 vs 37.5% in G3 for the former and 80% in G1 vs 50% in G3 for the latter, respectively), whereas CEA showed no relevant difference regarding the grading. There were no differences among the three antigens studied with regard to clinical stage. CONCLUSIONS: In our study Ber-EP4 was positive in 14 out of 22 cases (63.6%) of the primary epithelial ovarian cancers studied. The presence of this antigen seems to be related to histotype and grading but not to clinical stage.

Prognostic value of p53, c-erb-B2 and MIB-1 in endometrial carcinoma.

OBJECTIVE: To assess the immunohistochemical expression of p53 protein, a tumour suppressor gene of the oncogene c-erb-B2 and MIB-1 proliferation marker (Ki-67 antigen) in endometrial carcinoma. METHODS: We studied 29 cases of endometrial carcinoma in which the p53, c-erb-B2 and MIB-1/Ki-67 antigens were investigated by an immunohistochemical method. We evaluated the correlations among the immunohistochemical positivity and the grading, depth of myometrial invasion, stage of the neoplasia and follow-up. RESULTS: Both p53 and c-erb-B2 were positive in 16 out of 29 cases (55.2%), whereas MIB-1 was positive in 19 out of 29 cases (65.5%). All these three antigens showed a positive correlation with the grading, myometrial invasion and FIGO stage. Regarding follow-up, p53, c-erb-B2 and MIB-1 were, respectively, positive in 100%, 83.4% and 66.7% of neoplasias of patients who died of disease whereas they were positive in 40%, 40% and 60%, respectively, of tumours of patients with no evidence of disease. CONCLUSION: The overexpression of p53, c-erb-B2 and MIB-1 seem to indicate a more malignant tumour phenotype.

[Blue nevus of the uterine cervix: description of a case and review of the literature]. / Il nevo blu della cervice uterina: descrizione di un caso e revisione della letteratura.

Blue nevus is a pigmented lesion of dermal melanocytes; the extracutaneous locations are uncommon. We report a case of a blue nevus of the uterine cervix in a 53 years old woman, with histochemical and immunohistochemical investigations.

Identification of a founder BRCA2 mutation in Sardinia.

Sardinian population can be instrumental in defining the molecular basis of cancer, using the identity-by-descent method. We selected seven Sardinian breast cancer families originating from the northern-central part of the island with multiple affected members in different generations. We genotyped 106 members of the seven families and 20 control nuclear families with markers flanking BRCA2 locus at 13q12-q13. The detection of a common haplotype shared by four out of seven families (60%) suggests the presence of a founder BRCA2 mutation. Direct sequencing of BRCA2 coding exons of patients carrying the shared haplotype, allowed the identification of a 'frame-shift' mutation at codon 2867 (8765delAG), causing a premature termination-codon. This mutation was found in breast cancer patients as well as one prostate and one bladder cancer patient with shared haplotype. We then investigated the frequency of 8765delAG in the Sardinian breast cancer population by analysing 270 paraffin-embedded normal tissue samples from breast cancer patients. Five patients (1.7%) were found to be positive for the 8765delAG mutation. Discovery of a founder mutation in Sardinia through the identity-by-descent method demonstrates that this approach can be applied successfully to find mutations either for breast cancer or for other types of tumours.

Congenital mesoblastic nephroma (CMN) with an unusual immunohistochemical feature.

OBJECTIVES: To describe a case of congenital mesoblastic nephroma (CMN) treated by radical nephrectomy with no evidence of relapses after five years in spite of an unusual positivity for proliferating cellular nuclear antigen (PCNA). METHODS: A three-month-old child presented a right renal mass with compression of the inferior vena cava. Excretory urography showed an intrarenal mass with distortion of the calyceal system. There was no evidence of metastasis. Radical nephrectomy was carried out; no adjuvant therapy was given. Histological and immunohistochemical studies were performed. RESULTS: The tumor was a 6 x 6 x 5 cm solitary mass extending into perirenal tissue, involving the hilar vessels but not the ureter. Histologically, it has been classified as a congenital mesoblastic nephroma of the classic variant. Positive reaction for vimentin and actin was observed. Strong positivity for PCNA and negativity for P53 were revealed. CONCLUSIONS: PCNA is considered to be a reliable marker of potential malignancy. This, however, contrasts with the biological behavior of our case. Further evaluation is required for correct interpretation of this additional information and to avoid inappropriate aggressive therapy.

Neuron-specific enolase (gamma enolase, gamma-gamma dimer) expression in Hodgkin's disease and large cell lymphomas.

BACKGROUND: The presence of gamma-enolase, gamma gamma dimer, or neuron-specific enolase (NSE) has been demonstrated in miscellaneous tumors, including malignant lymphomas. Up to now these results have been interpreted as non-specific, although NSE can be expressed by normal B and T lymphoid cells at a particular stage of differentiation. The aim of the present study was to investigate the expression of NSE in a large series of malignant lymphomas, including Hodgkin's disease, in relation to morphology and immunophenotype. MATERIALS AND METHODS: Frozen and paraffin embedded sections from 16 cases of Hodgkin's disease (4 lymphocyte predominance, nodular; 4 mixed cellularity; 6 nodular sclerosis; 2 lymphocyte depletion) and 35 cases of non-Hodgkin's lymphomas were investigated in order to evaluate the expression of NSE, its specificity and correlation to immunophenotype or other immunological cell markers. Among the non-Hodgkin's lymphomas, there were 9 Anaplastic Large Cell (CD30+) Lymphomas; 2 Peripheral Large T-Cell Lymphomas; 22 Diffuse Large B-Cell Lymphomas and 2 Primary Mediastinal Large B-Cell Lymphomas. RESULTS: In Hodgkin's disease, NSE showed a diffuse cytoplasmic reaction in CD30+ Reed-Sternberg cells, whereas the "popcorn" (L&H) cells of lymphocyte predominance, nodular variant cases, were always negative. Among the non-Hodgkin's lymphomas, NSE positivity was found only in lymphomas expressing CD30. All the other cases were negative. No relationship was found between NSE and B- or T-immunophenotype. CONCLUSIONS: Our results suggest that a link between NSE and CD30 expression exists in malignant lymphomas. However, at the moment this has not been sufficiently investigated and is subject to speculation.