Granulomatous Slack Skin With Lung and Esophagus Involvement: A Case Report and Molecular Analysis.

ABSTRACT: Granulomatous slack skin (GSS) is a rare subtype of mycosis fungoides, and few cases have been known to spread to the blood, lymph nodes, or viscera. We present a case with early dissemination to the lung. A 27-year-old woman, previously healthy, presented with scattered disseminated scaly patches, associated with vulvar and intergluteal firm swelling and groin-skin induration for 1 year. She also reported mild fatigue and breathlessness on moderate exertion. The patient underwent blood tests, skin biopsies, and computed tomography scan. The skin biopsy showed a mildly atypical T-cell lymphoid infiltrate involving the dermis/hypodermis, with focal epidermotropism, associated with a granulomatous infiltrate and elastophagocytosis. The computed tomography scan revealed bilateral ground-glass lung nodular opacities. Positron emission tomography showed an increased signal in the skin and subcutis around the buttocks, inguinal and mediastinal lymph nodes, and lungs. The lung biopsy confirmed a dense T-cell infiltrate with numerous multinucleated giant cells. Subsequently, esophageal involvement was also observed following biopsy. Molecular analyses demonstrated identical T-cell clones in the skin and lung. After 6 cycles of chemotherapy/localized external radiotherapy, the patient had a partial skin response and stable lung disease. A preferred diagnosis of GSS with systemic spread was made based on clinical/histologic/molecular findings, after considering granulomatous mycosis fungoides and peripheral T-cell lymphoma, not otherwise specified. This case highlights the frequent diagnostic difficulty in distinguishing GSS from an inflammatory granulomatous dermatitis. Pulmonary and esophageal involvements are rare in GSS, and the simultaneous presentation of characteristic cutaneous GSS with systemic disease poses an additional classification challenge.

Increased cerebral endothelium-dependent vasodilation in rats in the postcardiac arrest period.

Cardiovascular lability is common after cardiac arrest. We investigated whether altered endothelial function is present in cerebral and mesenteric arteries 2 and 4 h after resuscitation. Male Sprague-Dawley rats were anesthetized, intubated, ventilated, and intravascularly catheterized whereupon rats were randomized into four groups. Following 7 min of asphyxial cardiac arrest and subsequent resuscitation, cardiac arrest and sham rats were observed for either 2 or 4 h. Neuron-specific enolase levels were measured in blood samples. Middle cerebral artery segments and small mesenteric arteries were isolated and examined in microvascular myographs. qPCR and immunofluorescence analysis were performed on cerebral arteries. In cerebral arteries, bradykinin-induced vasodilation was inhibited in the presence of either calcium-activated K+ channel blockers (UCL1684 and senicapoc) or the nitric oxide (NO) synthase inhibitor, Nω-nitro-L-arginine methyl ester hydrochloride (l-NAME), whereas the combination abolished bradykinin-induced vasodilation across groups. Neuron-specific enolase levels were significantly increased in cardiac arrest rats. Cerebral vasodilation was comparable between the 2-h groups, but markedly enhanced in response to bradykinin, NS309 (an opener of small and intermediate calcium-activated K+ channels), and sodium nitroprusside 4 h after cardiac arrest. Endothelial NO synthase and guanylyl cyclase subunit α-1 mRNA expression was unaltered after 2 h, but significantly decreased 4 h after resuscitation. In mesenteric arteries, the endothelium-dependent vasodilation was comparable between corresponding groups at both 2 and 4 h. Our findings show enhanced cerebral endothelium-dependent vasodilation 4 h after cardiac arrest mediated by potentiated endothelial-derived hyperpolarization and NO pathways. Altered cerebral endothelium-dependent vasodilation may contribute to disturbed cerebral perfusion after cardiac arrest.NEW & NOTEWORTHY This is the first study, to our knowledge, to demonstrate enhanced endothelium-dependent vasodilation in middle cerebral arteries in a cardiac arrest rat model. The increased endothelium-dependent vasodilation was a result of potentiated endothelium-derived hyperpolarization and endothelial nitric oxide pathways. Immunofluorescence microscopy confirmed the presence of relevant receptors and eNOS in cerebral arteries, whereas qPCR showed altered expression of genes related to guanylyl cyclase and eNOS. Altered endothelium-dependent vasoregulation may contribute to disturbed cerebral blood flow in the postcardiac arrest period.

P16 and HPV Genotype Significance in HPV-Associated Cervical Cancer-A Large Cohort of Two Tertiary Referral Centers.

The expression of p16 is a good surrogate of human papillomavirus (HPV) infection in HPV-associated cancers. The significance of p16 expression, HPV genotype and genera in the outcome of patients with HPV-associated cervical cancer (CC) is unclear. Our aim is to ascertain the prognostic significance of these factors. Data from 348 patients (median age: 47.5 years old) with CC, diagnosed in two referral centers, were retrospectively collected. Advanced disease (FIGO2018 IB2-IV) was present in 68% of patients. A single HPV genotype was identified in 82.8% of patients. The most common HPVs were HPV16 (69%) and HPV18 (14%). HPV genera reflected this distribution. HPV16 tumors presented at an earlier stage. P16 was negative in 18 cases (5.2%), 83.3% of which were squamous cell carcinomas. These cases occurred in older patients who tended to have advanced disease. In the univariate analysis, HPV16 (HR: 0.58; p = 0.0198), α-9 genera (HR: 0.37; p = 0.0106) and p16 overexpression (HR: 0.54; p = 0.032) were associated with better survival. HPV16 (HR: 0.63; p = 0.0174) and α-9 genera (HR: 0.57; p = 0.0286) were associated with less relapse. In the multivariate analysis, only the International Federation of Gynecology and Obstetrics (FIGO) stage retained an independent prognostic value. HPV16, α-9 genera and p16 overexpression were associated with better survival, although not as independent prognostic factors. Patients with p16-negative HPV-associated CC were older, presented with advanced disease and had worse prognosis.

HDAC Overexpression in a NUT Midline Carcinoma of the Parotid Gland with Exceptional Survival: A Case Report.

NUT midline carcinoma (NMC) is a recently described entity with a predilection for young individuals, characterised by a rearrangement of NUT, most commonly with BRD4. It usually involves midline structures, with a minority of cases presenting outside the midline axis. Given its dismal prognosis, new molecularly targeted therapies (eg, HDAC inhibitors) are gaining ground, but the HDAC expression pattern remains unknown. We describe the exceptional evolution of a NMC arising in the parotid gland. A 34-year-old male presented with a rapidly growing 35 mm left-parotid mass. Parotidectomy and lymphadenectomy were performed. The tumour invaded the surrounding soft tissue and lay adjacent to the surgical margin. No lymph node metastases were identified. Histology revealed blue nests of undifferentiated cells merging with foci of necrosis and occasional abrupt foci of keratinising squamous epithelium. FISH analysis confirmed a rearrangement of NUT, but not of BRD4. A diagnosis of NMC was rendered. Currently, after adjuvant chemoradiotherapy and 47 months after diagnosis, the patient is alive and well. The tumour was found to have increased immunoexpression of HDAC2, 4 and 6 and phospho-HDAC4/5/7. This case emphasises the importance of considering NMC in the differential diagnosis of poorly differentiated carcinomas of the head and neck region in young adults, even away from midline structures. As molecular targets hold the promise of successful therapy for the vast majority of NMC patients, the knowledge of their HDAC expression patterns will probably be relevant.

Fine-needle aspiration of lipoblastoma: Cytological, molecular, and clinical features.

BACKGROUND: Lipoblastomas are rare, benign adipocytic tumors that present mostly during infancy. In about 70% of cases, these tumors carry abnormalities in chromosome 8, mainly leading to rearrangements of the PLAG1 gene. METHODS: We report a series of histologically proven lipoblastomas with previous fine-needle aspiration (FNA) cytology from 9 patients (n = 10 samples) and describe their clinical, cytological, and molecular features. RESULTS: Our cohort included 5 boys and 4 girls (median age, 2.5 years [range, 10 months to 13 years]) who presented with soft tissue masses in the thorax (n = 3), abdomen (n = 2), axilla (n = 2), and thigh (n = 2). In 1 patient, the FNA diagnosis was inconclusive due to hypocellularity, and in another patient a diagnosis of benign lipomatous tumor was made. In the remaining 8 samples (one of which confirmed relapse), a correct preoperative FNA diagnosis was rendered. Smears were hypo- to moderately cellular and contained fragments of mature adipose tissue with thin branching vessels admixed with some lipoblasts in a myxoid matrix. Spindle cells and naked oval nuclei with no atypia were observed in the background. Of the 4 patients tested for PLAG1 rearrangement using FISH probes, 3 harbored this alteration (1 was made on a FNA smear and 1 was made in a tumor imprint). All the patients are alive and well, except for 1 patient with a retroperitoneal tumor who, after an initial incomplete excision, died of local disease progression. CONCLUSION: FNA, especially if used together with molecular biology techniques (eg, PLAG1 FISH analysis), is a reliable and accurate diagnostic tool. Cancer Cytopathol 2017;125:934-9. © 2017 American Cancer Society.

Invasive lobular carcinoma: a rare presentation in the male breast.

Breast cancer in men is uncommon, accounting for <1% of all breast cancers. Even though lobular structures are quite infrequent in the male breast, rare cases of invasive lobular breast carcinoma have been described, representing 1-2% of all breast cancers in men. Risk factors include undescended testes, congenital inguinal hernia, orchiectomy, orchitis, testicular injury, infertility and Klinefelter's syndrome, previous thoracic radiotherapy, alterations of the oestrogen-testosterone ratio and familial history (BRCA 2 and 1). The authors present a case of a 52-year-old man with no relevant predisposing factors to breast cancer, who presented with a painless, firm nodule, fixed to the nipple on the left breast, associated with nipple retraction and ulceration, and fully characterised by mammogram and ultrasound. Histopathological and immunohistochemical analysis revealed the diagnosis of invasive lobular breast carcinoma and the patient underwent left radical mastectomy, followed by adjuvant chemotherapy, radiotherapy and hormonotherapy. A brief review of the literature is presented.

A rare benign ovarian tumour.

Sclerosing stromal tumour (SST) of the ovary is an extremely rare and benign ovarian neoplasm, accounting for 6% of the sex cord stromal ovarian tumours subtype. Usually, it is found during the second and third decades of life. Patients commonly present with pelvic pain, a palpable pelvic mass or menstrual irregularity. We report a case of a 20-year-old woman reporting of mild pelvic pain, with normal laboratory data. On imaging examinations, a large right adnexal tumour was found, with features suggesting an ovarian sex cord tumour. The patient underwent right salpingo-oophorectomy, diagnosing a SST of the ovary. This paper also reviews the literature, and emphasises the typical pathological and imaging characteristics of these rare benign ovarian lesions, and their impact, in a conservative surgery.