Management of breast lobular carcinoma in situ: radio-pathological correlation, clinical implications, and follow-up.

PURPOSE OF INVESTIGATION: To show management of patients with breast lobular carcinoma in situ (LCIS). MATERIALS AND METHODS: This study is the retrospective review of 65 patients, between 1996 and 2012, with isolated LCIS of the breast, evaluated through clinical examination, ultrasound, and mammography at the first examination and follow-up. RESULTS: In 53 patients (81.54%), clinical examination was negative. In 14/65 (21.54%) cases, ultrasound was positive and led to biopsy. The clusters of tiny calcifications were the predominant mammographic pattern (45 cases, 69.23%). Forty-six patients (70.77%) underwent surgical biopsy after guided stereotactic placement of metallic marker (hook-wire), 12 (18.46%) by stereotactic vacuum biopsy (SVB), 5 (7.69%) by core needle biopsy (CNB) under ultrasound guidance, two (3.08%) patients CNB with clinically palpable nodules. Fourteen (21.54%) women underwent a quadrantectomy or total mastectomy after the first diagnosis; in this latter group follow-up was negative. Among the 51 patients (78.46%) who did not undergo quadrantectomy or total mastectomy, five relapses occurred, respectively, three LCIS and two infiltrating ductal carcinomas (IDC). Follow-up ranged from 12 to 144 months. CONCLUSION: LCIS is a risk factor for invasive carcinoma and should be managed with careful follow-up, but if there is a discrepancy between pathology and imaging, surgical excision is mandatory.

Proteomic characterization of hepatitis C eradication: enzyme switch in the healing liver.

Lipid pathway impairment, decrease in the antioxidant pool and downregulation in amino-acid metabolism are just some of the metabolic variations attributed to chronic HCV infection. All of them have been studied separately, mainly in animal models. Thanks to proteomic analysis we managed to describe (for the fist time to the best of our knowledge), in vivo and in humans, the metabolic alterations caused by HCV, and the recovery of the same alterations during HCV treatment. We performed proteomic analysis on liver specimens of a 28-year-old woman affected by hepatitis C genotype 1a, alcoholism and diabetes mellitus type 1, before and after antiviral treatment with pegylated interferon alpha 2b and ribavirin. The subject, thanks to a patient-tailored therapy, reached Sustained Virological Response. Throughout the treatment period the patient was monitored with subsequent biochemical, clinical and psychological examinations. The data obtained by the patient's close monitoring suggest a direct interaction between insulin resistance and an active HCV genotype 1 infection, with a leading role played by the infection, and not by insulin resistance, as demonstrated by the sharp fall of the insulin units needed per day during treatment. The proteomic analysis showed that after therapy, a downregulation of enzymes involved in amino acid metabolism, glycolysis/gluconeogenesis and alcohol catabolism takes place, the latter probably due to cessation of alcohol abuse. On the contrary, the metabolic pathways linked to metabolism of the reactive oxygen species were upregulated after therapy. Finally, a significant alteration in the pathway regulated by peroxisome proliferator-activated receptor alpha (PPARA), a major regulator of lipid metabolism in the liver, was reported. These "real time" data confirm in vivo, in humans, that during HCV infection, the pathways related to fatty acids, glucose metabolism and free radical scavenging are inhibited. The same enzyme deficit is completely recovered after HCV eradication.

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.

Rhabdomyosarcoma: a rare laryngeal neoplastic entity.

A case of pleomorphic rhabdomyosarcoma of the larynx is presented, which is extremely rare in a laryngeal site. The symptomatology and macroscopic aspect of the neoplasm can simulate the presence of other neoplastic variants of the larynx, and, for this reason, histological examination must be associated with immunohistochemistry for correct diagnosis and treatment.

Bilateral ovarian malignant mixed Mullerian tumor in a dog.

Malignant mixed Müllerian tumor (MMMT) is a rare neoplasm of the female genital tract. We report a case of bilateral ovarian MMMT in a 10-year-old female dog. Ovaries were only moderately enlarged with a papillary surface and firm nodules. Multiple metastases were observed in the abdominal cavity and pulmonary parenchyma. Histologically, both ovaries had intermingled carcinomatous and sarcomatous components with cartilage and bone. Metastatic lesions were not mixed. The peritoneal metastases were carcinomatous; pulmonary metastases were sarcomatous. Carcinomatous elements of the MMMT were immunohistochemically positive for cytokeratin (CK) AE1/AE3, CK7, and vimentin and estrogen receptors. Conversely, the sarcomatous cells were positive for vimentin, but negative for CKs. Chondrocytes also expressed S-100 protein. On the basis of similarities to human ovarian MMMT, the diagnosis was heterologous malignant mixed Müllerian tumor of the ovary.

Fluorescent cytogenetics of renal cell neoplasms.

Renal cell neoplasms are a heterogeneous group of tumours in terms of pathological features and prognostic behaviour. The genetics of these tumours may aid in correct diagnosis and accurate assessment of prognosis. In ambiguous cases it may be necessary to utilise new markers that are capable of further discerning renal cell neoplasms. Fluorescence in situ hybridization (FISH) on formalin-fixed, paraffin-embedded tissue is an increasingly useful technique in the detection of many diagnostic chromosomal abnormalities, among which chromosomes 1, 2, 3p, 6, 7, 10, 17 and Y are the most common. The addition of FISH to histological evaluation improves the diagnostic accuracy of core biopsies from renal masses, which may have an important impact in clinical management of many cases due to newer therapeutic approaches, including cryo- or radiofrequency ablation, nephron-sparing surgeries and target therapies.

OCT4: biological functions and clinical applications as a marker of germ cell neoplasia.

Germ cell tumours (GCTs) are a heterogeneous group of neoplasms, which develop in the gonads as well as in extragonadal sites, that share morphological patterns and an overall good prognosis, owing to their responsiveness to current surgical, chemotherapeutic, and radiotherapeutic measures. GCTs demonstrate extremely interesting biological features because of their close relationships with normal embryonal development as demonstrated by the pluripotentiality of some undifferentiated GCT variants. The similarities between GCTs and normal germ cell development have made it possible to identify possible pathogenetic pathways in neoplastic transformation and progression of GCTs. Genotypic and immunophenotypic profiles of these tumours are also useful in establishing and narrowing the differential diagnosis in cases of suspected GCTs. Recently, OCT4 (also known as OCT3 or POU5F1), a transcription factor that has been recognized as fundamental in the maintenance of pluripotency in embryonic stem cells and primordial germ cells, has been proposed as a useful marker for GCTs that exhibit features of pluripotentiality, specifically seminoma/dysgerminoma/germinoma and embryonal carcinoma. The development of commercially available OCT4-specific antibodies suitable for immunohistochemistry on paraffin-embedded specimens has generated increasing numbers of reports of OCT4 expression in a wide variety of gonadal and extragonadal GCTs. OCT4 immunostaining has been shown to be a sensitive and specific marker for seminomatous/(dys)germinomatous tumours and in embryonal carcinoma variants of non-seminomatous GCTs, whether in primary gonadal or extragonadal sites or in metastatic lesions. Therefore, OCT4 immunohistochemistry is an additional helpful marker both in the differential diagnosis of specific histological subtypes of GCTs and in establishing a germ cell origin for some metastatic tumours of uncertain primary. OCT4 expression has also been reported in pre-invasive conditions such as intratubular germ cell neoplasia, unclassified (IGCNU) and the germ cell component of gonadoblastoma. Additionally, OCT4 immunostaining shows promise as a useful tool in managing patients known to be at high risk for the development of invasive GCTs.

BRCA1 and BRCA2 germline mutations in Sardinian breast cancer families and their implications for genetic counseling.

BACKGROUND: The Sardinian population is genetically homogeneous and could be useful in understanding better the genetics of a complex disease like breast cancer (BC). PATIENTS AND METHODS: Using a screening assay based on a combination of single-strand conformation polymorphism, denaturing high-performance liquid chromatography and sequence analysis, 47 Sardinian families with three or more BC cases were screened for germline mutations in BRCA1 and BRCA2 genes. RESULTS: Three BRCA1/2 germline sequence variants were identified. While BRCA2-Ile3412Val is a missense variant with unknown functional significance, BRCA2-8765delAG and BRCA1-Lys505ter are two deleterious mutations (due to their predicted effects on protein truncation), which were found in seven families (15%). BRCA2-8765delAG was found in six of eight (75%) BRCA1/2-positive families and seven of 501 (1.4%) unselected and consecutively collected BC patients. Prevalence of BRCA1/2 mutations in BC families was significantly correlated with the total number of female BCs (P <0.01) and increased by the presence of (i) at least one case of ovarian or male BC, or (ii) three generations affected, or (iii) bilateral BC. CONCLUSIONS: Identification of such features should address BC patients and their families to genetic counseling and BRCA1/2 mutational analysis. In addition, this is the first report of a detailed BRCA1/2 mutation screening in Sardinia, having immediate implications for the clinical management of BC families.

Rectal endometrial stromal sarcoma arising in endometriosis: report of a case.

PURPOSE: Endometriosis of the rectovaginal septum can harbor different types of secondary tumors that may involve the rectal wall and protrude into its lumen, thus making diagnosis difficult. Extrauterine low-grade endometrial stromal sarcoma may rarely arise in endometriosis. The purpose of this article was to present the third case of this association. METHOD: This was a clinicopathologic study. RESULTS: A 42-year-old female presented with abdominal pain and fever. Laparotomy revealed a large pelvic mass involving the rectovaginal septum and the colonic wall and which protruded into the lumen forming endoluminal polypoid masses. Concomitant peritoneal nodules and a metastatic paracolic lymph node were also found. Histopathologically, primary endometriotic foci were found in close relationship with an endometrial stromal sarcoma which invaded the rectal wall. The female genital tract had no endometriotic lesions. The patient was treated by surgery and subsequent chemotherapy and was alive and well 20 months later. CONCLUSIONS: Endometriosis and its possible malignant changes should be taken into account in the differential endoscopic diagnosis of rectal masses in females.

Immunohistochemical expression of BerEP4, a new epithelial antigen, in endometrial carcinoma: correlation with clinical parameters.

OBJECTIVE: To assess the immunochemical expression of BerEP4, a new epithelial antigen in endometrial carcinoma. METHODS: We studied 45 cases of endometrial carcinoma in which the BerEP4, CEA and TAG-72 antigens were searched by an immunohistochemical method. We evaluated the correlations among the immunohistochemical positivity and the grading, histotype, stage and receptorial status of the neoplasia. RESULTS: CEA was positive in 29 out of 45 cases (64.4%), TAG-72 in 17 out of 45 cases (37.7%) and BerEP4 in 31 out of 45 cases (68.9%). Both TAG-72 and CEA were inversely related to the grading while, with regard to the histotype, CEA resulted as highly positive in the 5 cases of adenoacanthoma. CONCLUSION: BerEP4 did not show any correlation with grading, histotype, stage of disease or receptorial status of the carcinoma.

Uterine metastases from breast cancer in a patient under tamoxifen therapy. Case report.

The authors report a case of metastases of breast cancer confined to the uterus and cervical subserous leiomyoma in a postmenopausal woman under tamoxifen therapy for two years. After abnormal uterine bleeding, pathologic examination on biopsy of a cervical polyp revealed cervical involvement secondary to lobular breast cancer. The patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy. Pathologic examination of the surgical specimen revealed both invasion of breast origin and of the cervix until the isthmus, endometrium and cervical subserous leiomyoma. The adnexa uteri were not affected. The possibility of uterine metastases in patients suffering from breast cancer, either undergoing tamoxifen therapy or not, always has to be considered.

A case of primary hydatidosis of the thyroid gland.

A 54-year-old woman presented with an expansive mass in the anterior cervical region (front of the neck) with abscess. Laboratory tests and thyroid profile proved normal. Surgical exploration revealed a hydatid cyst in the left lobe of the thyroid gland with parasitic metastasis of the left lateral cervical lymph node chain. Postoperative examination of the nodule showed it to be a solitary primary thyroid hydatid cyst.

A case of primary hydatidosis of the thyroid gland.

A 54-year-old woman presented with an expansive mass in the anterior cervical region (front of the neck) with abscess. Laboratory tests and thyroid profile proved normal. Surgical exploration revealed a hydatid cyst in the left lobe of the thyroid gland with parasitic metastasis of the left lateral cervical lymph node chain. Postoperative examination of the nodule showed it to be a solitary primary thyroid hydatid cyst.

Effectiveness of "core biopsy" by the mammotome device for diagnosis of inflammatory carcinoma.

OBJECTIVE: To assess the usefulness of "Mammotome" device for the diagnosis of the inflammatory breast carcinoma. MATERIAL AND METHODS: We studied 6 patients, aged 43-79 years, with clinical evidence of inflammatory breast carcinoma. We compared two sampling techniques, a cytologic one by Fine Needle Aspiration (FNA) and a microhistologic one by "Mammotome". RESULTS: Cytologic sampling by FNA permitted certain diagnosis of malignant lesions in 2 out of 6 cases, while the "Mammotome" device confirmed the correct diagnosis in all 6 considered cases. CONCLUSIONS: The "Mammotome" device proved more useful in the diagnosis of inflammatory breast carcinoma than FNA and it can be a valide alternative to surgical biopsy.

[Sutures without sutures in digestive surgery. Experimental study of the rat intestine]. / Suture senza suture in chirurgia digestiva. Studio sperimentale sull'intestino del ratto.

The aim of the experimental study was to evaluate the possibility of performing an end-to-end anastomosis by using fibrin adhesive as the only means of suture. To this end, 24 Wistar rats were used, of which 16 underwent ilear resection and 8 underwent colotomy, and they were divided respectively into two groups. On the rats of the first group the anastomosis was performed by using only fibrin adhesive; on the rats of the second group operated the anastomosis was performed by using fibrin adhesive in association with non adsorbable suture material, while on those operated of colectomy the anastomosis was performed by fibrin adhesive and adsorbable suture material. The anatomo-phatological studies on the anastomosis have shown a similar healing process in the cases treated only with fibrin adhesive and by using absorbable material and has demonstrated the trange material from the suture, which are a possible causes of complication.