Mixed Neuroendocrine/Non-neuroendocrine Neoplasm (MiNEN) of the Ovary Arising from Endometriosis: Molecular Pathology Analysis in Support of a Pathogenetic Paradigm.

Primary ovarian neuroendocrine neoplasms (Ov-NENs) are infrequent and mainly represented by well-differentiated forms (neuroendocrine tumors - NETs - or carcinoids). Poorly differentiated neuroendocrine carcinomas (Ov-NECs) are exceedingly rare and only few cases have been reported in the literature. A subset of Ov-NECs are admixed with non-neuroendocrine carcinomas, as it occurs in other female genital organs, as well (mostly endometrium and uterine cervix), and may be assimilated to mixed neuroendocrine/non-neuroendocrine neoplasms (MiNENs) described in digestive and extra-digestive sites. Here, we present a case of large cell Ov-NEC admixed with an endometrioid carcinoma of the ovary, arising in the context of ovarian endometriosis, associated with a uterine endometrial atypical hyperplasia (EAH). We performed targeted next-generation sequencing analysis, along with a comprehensive immunohistochemical study and FISH analysis for TP53 locus, separately on the four morphologically distinct lesions (Ov-NEC, endometrioid carcinoma, endometriosis, and EAH). The results of our study identified molecular alterations of cancer-related genes (PIK3CA, CTNNB1, TP53, RB1, ARID1A, and p16), which were present with an increasing gradient from preneoplastic lesions to malignant proliferations, both neuroendocrine and non-neuroendocrine components. In conclusion, our findings underscored that the two neoplastic components of this Ov-MiNEN share a substantially identical molecular profile and they progress from a preexisting ovarian endometriotic lesion, in a patient with a coexisting preneoplastic proliferation of the endometrium, genotypically and phenotypically related to the ovarian neoplasm. Moreover, this study supports the inclusion of MiNEN in the spectrum ovarian and, possibly, of all gynecological NENs, among which they are currently not classified.

Plasmablastic lymphoma presenting as a brachial artery aneurysm associated with haemodialysis arteriovenous access ligation in a renal transplant patient.

INTRODUCTION: Plasmablastic lymphoma is a rare and aggressive neoplasm, generally associated with immunodeficiencies and related to latent Epstein-Barr virus infection. This case is the first reported case of plasmablastic lymphoma relapse in aneurysmatic brachial artery wall. CASE DESCRIPTION: We describe the case of male patient who underwent cadaveric donor kidney transplant when he was 61 years old and radio-cephalic distal arteriovenous fistula ligation 8 months later. After 8 years, he developed gingival plasmablastic lymphoma treated with cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone regimen with subsequent remission. During follow-up, a mid-forearm vascular access was created because of the worsening of renal function. Twenty-two months later, the patient showed a symptomatic 20 mm brachial artery aneurysm with radiological signs of imminent rupture, for which he was surgically treated. The histological evaluation of the brachial artery specimen revealed a relapse of plasmablastic lymphoma in the arterial wall and in an adjacent lymph node. CONCLUSION: Brachial artery aneurysms are a rare complication in kidney transplant recipients after ligation of arteriovenous access for haemodialysis. Here, we report a case in which this condition is associated with an even rarer plasmablastic lymphoma. A common aetiology, due to immunosuppressive therapy, is postulated for the two coexisting diseases.

Disease heterogeneity in IgG4-related hypophysitis: report of two histopathologically proven cases and review of the literature.

IgG4-related hypophysitis (IgG4-RH) is a rare disease, which can occur singularly or as manifestation of a systemic IgG4-related disease (IgG4-RD). Less than one hundred cases have been reported in the literature, very few of which were histopathologically documented. We analyzed the clinical, radiological, and histopathological features of two cases of IgG4-RH, the former observed in a 66-year-old man in the context of an IgG4-RD, and the latter affecting a 21-year-old woman, as an isolated lesion. In addition, we performed a comprehensive review of the previously published histopathologically documented cases of IgG4-RH. Pituitary samples from both patients showed dense lymphoplasmacytic infiltration, interstitial and storiform fibrosis, and high numbers of IgG4-positive plasma cells, consistent with IgG4-RH. From the literature review, we retrieved 18 papers reporting a total of 22 cases of histopathologically documented IgG4-RH. The revision of these cases, also including the two reported herein, showed an equal distribution of IgG4-RH in the two sexes, albeit significant clinico-pathological variation was found between cases arisen in female and male patients, respectively. In detail, IgG4-RH females were affected in their second-third decade of life, with a solitary pituitary lesion, low IgG4 serum level, and frequent association with autoimmune disorders. By contrast, IgG4-RH in men was a disease of the elderly, often in the context of a systemic IgG4-RD, with high IgG4 serum levels. Our study shows that IgG4-RH, as currently defined, is a clinically heterogenous disease, with different features in the two sexes. Indeed, cases diagnosed in young women, as our case 2, mostly do not present other evidence of IgG4-RD and might be better classified as lymphocytic hypophysitis with abundant IgG4+ plasma cells. For this reason, the histopathological examination of the pituitary lesion, particularly in female patients, may still be useful for a correct differential diagnosis with other variants of primary hypophysitis.