Paraoxonase-2 is upregulated in triple negative breast cancer and contributes to tumor progression and chemoresistance.

Triple negative breast cancer (TNBC) displays a high aggressive behavior, tendency to relapse and early metastasize, leading to poor prognosis. The lack of estrogen receptors, and human epidermal growth factor receptor 2, prevents the use of endocrine or molecular targeted therapy, being therapeutical options for TNBC managements mostly limited to surgery, radiotherapy and mainly chemotherapy. While an important number of TNBCs initially responds to chemotherapy, they are prone to develop chemoresistance over the time. Thus, there is an urgent need to identify novel molecular targets to improve the outcome of chemotherapy in TNBC. In this work we focused on the enzyme paraoxonase-2 (PON2) which has been reported to be overexpressed in several tumors contributing to cancer aggressiveness and chemoresistance. Through a case-control study, we analyzed PON2 immunohistochemical expression in breast cancer molecular subtypes Luminal A, Luminal B, Luminal B HER2+, HER2 + and TNBC. Subsequently, we evaluated the in vitro effect of PON2 downregulation on cell proliferation and response to chemotherapeutics. Our results showed that the PON2 expression levels were significantly upregulated in the infiltrating tumors related to the subtypes Luminal A, HER2+ and TNBC compared to the healthy tissue. Furthermore, PON2 downregulation led to a decrease in cell proliferation of breast cancer cells, and significantly enhanced the cytotoxicity of chemotherapeutics on the TNBC cells. Although further analyses are necessary to deeply understand the mechanisms by which the enzyme could participate to breast cancer tumorigenesis, our results seem to demonstrate that PON2 could represent a promising molecular target for TNBC treatment.

Ossifying trichilemmal cyst.

Although a trichilemmal cyst is a relatively common benign cutaneous condition and ossification has been observed within many cutaneous lesions to our knowledge, the association between ossification and trichilemmal cyst has not been previously reported. We describe for the first time the case of a trichilemmal cyst with marked osseous metaplasia arising on the scalp of a 46 year-old woman. Microscopically the lesion showed the typical features of a trichilemmal cyst with the finding of intra-extraluminal foci of calcification and the exceptional feature of mature bone formation. No areas of mature cartilage were observed near the focus of ossification. The cutaneous bone may have been directly formed from osteogenic stromal elements without a cartilaginous precursor (membranous or mesenchymal ossification). The dystrophic calcification might also contribute to the bone-forming process.

Abdominal-pelvic actinomycosis mimicking malignant neoplasm.

Abdominal-pelvic actinomycosis is often mistaken for other conditions, presenting a preoperative diagnostic challenge. In a 46-year-old female, computed tomography showed an abdominal-pelvic retroperitoneal mass extending from the lower pole of the right kidney to the lower pelvis. The patient had a 3-year history of intrauterine device. The mass appeared to involve the ascending colon, cecum, distal ileum, right Fallopian tube and ovary, and ureter anteriorly and the psoas muscle posteriorly. The resection of retroperitoneal mass, distal ileum appendicectomy, right hemicolectomy, and right salpingo-oophorectomy was performed. The postoperative period was uneventful. Penicillin therapy was given for six months without any complication. The retroperitoneal mass measured 4.5 × 3.5 × 3 cm, surrounded adjacent organs and histologically showed inflammatory granulomatous tissue, agglomeration of filaments, and sulfur granules of Actinomyces, with positive reaction with periodic acid Schiff. Right tubo-ovarian abscess was present. Abdominalpelvic actinomycosis should always be considered in patients with a pelvic mass especially in ones using intrauterine device.

Immunohistochemical expression of somatostatin receptor subtypes in prostate tissue from cystoprostatectomies with incidental prostate cancer.

OBJECTIVE: To examine immunohistochemically the expression of the five somatostatin receptors (SSTRs) in cystoprostatectomies (CyPs) with incidental prostate cancer. MATERIALS AND METHODS: The five SSTRs (SSTR1-5) were evaluated in 'normal-looking' epithelium (NEp), high-grade prostatic intraepithelial neoplasia (HGPIN) and pT2a Gleason score 6 adenocarcinoma in 20 CyP specimens with incidental prostate cancer and 20 radical prostatectomy (RP) specimens with clinically detected prostate cancer. RESULTS: For cytoplasm expression, the mean percentage of positive secretory cells with strong cytoplasmic staining increased from NEp to HGPIN and prostate cancer, being slightly lower in the CyP than in the RP specimens. Both in the CyP and RP specimens SSTR4 was found in the highest percentage of cells. There was membrane staining in the secretory cells for SSTR3 and SSTR4. There was nuclear staining in the secretory cells for SSTR4 and SSTR5. For SSTR1 and SSTR3 the mean proportions of positive basal cells were higher than for the other three subtypes, and greater in NEp than in HGPIN. There were positive smooth muscle and endothelial cells for all five SSTR subtypes, the highest proportions being SSTR1 and the lowest SSTR5. CONCLUSIONS: This immunohistochemical study expands our knowledge of the expression and localization of SSTRs in the various tissue components in the prostate with incidental cancer, compared with clinically detected cancer. Such information might be useful in developing further non-invasive strategies for the prevention and treatment of pre-neoplastic and neoplastic lesions of the prostate.

Secondary neoplasms of the urinary system and male genital organs.

BACKGROUND AND AIMS: In this review we discuss those secondary tumours involving the urinary system and male genital organs that can pose differential diagnostic difficulties with primary lesions, and highlight morphological and ancillary features that could be helpful in reaching a proper assignment of primary origin. MATERIALS AND METHODS: Based on MEDLINE database searches all reports of secondary tumours involving the urinary system (kidney and bladder) and male genital organs (prostate, testis and penis) were examined. RESULTS AND DISCUSSION: Involvement by a secondary tumour occurs either as a metastasis or by direct extension. Among non-genitourinary primary sites, colorectal, pulmonary, skin (melanoma) and breast are the most common contributors. Secondary spread from a genitourinary site primary tumour to another genitourinary organ occurs most frequently between the prostate and urinary bladder, given the intimate topographic proximity of the two. The prognosis is very poor, as the secondary tumour usually occurs in patients with carcinoma in the late stages. Few secondary tumours have distinctive histological and immunohistochemical features, making it difficult to make the appropriate diagnosis. Hence, knowledge of the history and clinical setting are particularly important in these cases. CONCLUSION: The urinary system and male genital organs are not common sites for secondary tumours. They often go either undiagnosed or misdiagnosed in the clinical follow-up of patients with cancer. Accurate diagnosis is essential because of differing therapeutic approaches compared with a primary neoplasm.

Neuroendocrine tumours of the urinary system and male genital organs: clinical significance.

Two basic types of neuroendocrine (NE) tumours with diverse clinicopathological features and outcome are identified in the urinary system and male genital organs: carcinoid tumour and neuroendocrine carcinoma. Carcinoid, a rare tumour, occurs in the kidney, bladder, prostate and testis. It is morphologically, histochemically, immunohistochemically and ultrastructurally similar to its counterpart in other organs, such as lung or gastrointestinal tract. Metastases can be detected at the initial evaluation, although they have been reported up to several years after removal, emphasizing the need for a long-term follow-up. NE carcinoma occurs in the kidney, bladder and prostate, and includes small cell carcinoma (SCC) and large cell NE carcinoma (LCNEC), the latter being exceedingly rare. Both show the morphology and immunophenotype of NE carcinoma originating in other organs. Although the occurrence is rare, it is highly aggressive.

Immunohistochemical detection and localization of somatostatin receptor subtypes in prostate tissue from patients with bladder outlet obstruction.

BACKGROUND AND AIM OF THE STUDY: Scant information on the cellular distribution of the five somatostatin receptor (SSTR) subtypes in the normal prostate and in neoplasms of the prostate has been reported in very few studies in which techniques, such as in situ hybridization histochemistry, autoradiography, and more recently immunohistochemistry, have been applied. The aim of the study was to examine immunohistochemically the distribution and localization of these 5 subtypes in the various tissue components in normal prostate. MATERIALS: The study was conducted in 14 surgical specimens of normal prostate tissue from adenomectomy specimens from patients with bladder outlet obstruction. The distribution and localization of the 5 somatostatin receptor (SSTR) subtypes was investigated with an immunohistochemical technique. Specificity of the antibodies against the 5 receptor subtypes was preliminarily investigated. RESULTS: Close to 90% of secretory cells showed a weak positivity in the cytoplasm, the proportion ranging from 86.3% (SSTR4) to 89.9% (SSTR5). Strong immunoreactivity was seen in a small proportion of cells, ranging from 0.8% (SSTR3) to 3.2% (SSTR1). For the subtypes 1 and 3 the greatest proportion of basal cells showed a moderate intensity (42.5 and 41.4%, respectively), strong immunoreactivity being observed only in 18.1 and 15.8% of cells, respectively. For the subtypes 2, 4 and 5, the majority of cells showed a weak intensity (72.3, 65.7 and 65.1%, respectively). Subtype 1 showed a strong immunoreactivity in the cytoplasm in 60% of the smooth muscle cells. With subtypes 2, 3 and 4 the greatest proportion of cells showed a weak intensity (63.4, 89.8 and 81.7%, respectively). With the subtype 5 the majority of cells (59.8%) were negative. Subtype 1 showed a strong immunoreactivity in the cytoplasm in 98.6% of the endothelial cells. With subtypes 3 and 4 the greatest proportion of cells showed a weak intensity (73.5 and 56.4%, respectively). With the subtype 2 and 5 the majority of cells were negative (59.1 and 50.7%, respectively).

Clinicopathological features of primary cutaneous B-cell lymphomas from an academic regional hospital in central Italy: no evidence of Borrelia burgdorferi association.

We reviewed the clinico-pathological features of 73 primary cutaneous B-cell lymphomas (PCBCLs), diagnosed in 10 years in Marche region in central Italy, which included 16 marginal zone lymphomas (MZL), 33 follicle centre lymphomas (FCL) and 24 diffuse large B cell lymphomas (DLBCL). We also investigated the presence of Borrelia burgdorferi in tissues by polymerase chain reaction. Differences in age, sex, location site, response to therapy, disease recurrence and 5-year disease-specific survival were observed among the 3 histological groups. Specific DNA sequences of Borrelia burgdorferi were not detected in any of the 73 cases of PCBCL. We conclude that PCBCLs in Marche region behave according to the literature data and do not seem to be associated with Borrelia burgdorferi. Additional investigations should be performed on other possible etiologies, at least in our geographical area.

Clinical Features, Dermoscopic Patterns, and Histological Diagnostic Model for Melanocytic Tumors of Uncertain Malignant Potential (MELTUMP).

Cutaneous melanocytic lesions with atypical histological features can be difficult to categorize as benign or malignant. In the diagnosis of melanocytic lesions, the melanocytic tumor of uncertain malignant potential (MELTUMP) category has been widely used. Although one may favor a benign or malignant interpretation, a definitive diagnosis is not always possible, and long term clinical follow-up remains the only true evidence of biological behavior. We report 14 cases of MELTUMP with expert second opinion. Clinical pictures were available in 8 cases; dermoscopy was available in 5 cases. Accurate guidelines are delineated in the formulation of the diagnosis. We think that the histological diagnosis should be accompanied by a note in which the pathologist describes the histological pattern that has generated diagnostic uncertainty. Since the MELTUMP term does not exclude the malignant nature of the lesion, all microstaging attributes for melanoma should be added. Moreover, superficial atypical melanocytic proliferation of uncertain significance (SAMPUS) and MELTUMP categories should be included in the WHO classification of melanocytic tumors of the skin. The role of sentinel lymph node biopsy in MELTUMP has not yet been established. Recent studies have looked at concurrent tumor deposits in lymph nodes of MELTUMP, mostly of atypical Spitzoid lesions, and shown that these lesions rarely progress to overt malignancy. In our study, sentinel node metastasis was found in only one case. The follow-up period of this case and of the others has shown that the clinical outcome of MELTUMP tends to be favorable.

Coexistence of atypical adenoma, adenoma with bizarre nuclei and follicular variant of papillary carcinoma of the thyroid.

Coexistence of atypical adenoma, adenoma with bizarre nuclei and follicular variant of papillary carcinoma is described in the same thyroid, with study of p53 expression. A 72-year-old woman presented to the endocrinology out-patient unit for a routine follow-up visit. Patient underwent a total thyroidectomy. Histological examination revealed a solid nodular neoplasm with the longest diameter of 0.8 cm in the upper pole of the left lobe. The neoplasm showed the histological features of follicular variant of papillary carcinoma with moderate diffuse immunoreactivity for p53. The lower pole of the right lobe showed two adjacent nodules with histological features respectively of atypical adenoma and adenoma with bizarre nuclei, with strong diffuse immunoreactivity for p53.

HMB-45 negative clear cell perivascular epithelioid cell tumor of the skin.

The first case of cutaneous clear cell perivascular epithelioid cell tumor (PEComa) with negative HMB-45 marker is presented. The tumor was a nodule 3x2 cm in size, located on the right foot in a 60-year-old man. The lesion consisted of large irregularly shaped cells with clear cytoplasm, negative for S-100 protein, HMB-45, Melan-A, pancytokeratin, epithelial membrane antigen and CAM5.2. Multifocal positivity for desmin, microphthalmia transcription factor and tyrosinase was found. The diagnosis of cutaneous PEComa of clear cell type was made. Clear cell change is a very unusual finding in PEComa and may pose problems in diagnostic differentiation from other clear cell cutaneous lesions that may be excluded with immunohistochemistry. In our case, the HMB-45 negativity may be explained by extensive clear cell change. Additional studies are necessary to accept the clear cell cutaneous HMB-45 negative PEComa as a new variant of perivascular epithelioid cell tumor.

Somatostatin receptor subtypes in hormone-refractory (castration-resistant) prostatic carcinoma.

The aim of this study was to examine the tissue expression and localisation of the somatostatin receptors (SSTRs) in hormone-refractory (HR) prostate cancer (PCa). Five SSTRs were evaluated immunohistochemically in 20 radical prostatectomies (RPs) with Gleason score (GS) 3+3=6 PCa, in 20 RPs with GS 4+4=8 and 4+5=9 PCa, and 20 transurethral resection of the prostate specimens with HR PCa. The mean values in the cytoplasm (all five SSTRs were expressed), membrane (only SSTR3 and SSTR4 were expressed) and nuclei (only SSTR4 and SSTR5 were expressed) of the glands in HR PCa were 20-70% lower than in the other two groups, the differences being statistically significant. All five SSTRs were expressed in the smooth muscle and endothelial cells of HR PCa, the mean values being lower than in the other two groups. In conclusion, this study expands our knowledge on the expression and localisation of five SSTRs in the various tissue components in the HR PCa compared with hormone-sensitive PCa.