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.

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.

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.