Haemangiomas in kidneys with end-stage renal disease: a novel clinicopathological association.

AIMS: The study of haemangiomas in end-stage renal disease (ESRD). METHODS AND RESULTS: Twenty ESRD nephrectomies from 16 patients (aged 9 months-68 years) were due to hypertension (four), focal segmental glomerulosclerosis (four), lupus nephritis (three), diabetes (one), IgA nephropathy (one), hereditary nephritis (one), congenital nephrotic syndrome (one) and unknown cause (one). Haemangiomas appeared as a single mass (15), two masses (one), three masses (one), four masses (two) and eight masses (one) per kidney. Tumours measured 0.2-3.5 cm. Four patients had bilateral haemangiomas. All tumours were in the medulla and often abutted renal sinus fat. All except one of the tumours were anastomosing haemangiomas, showing isolated or interconnected sinusoidal capillary-sized vascular channels lined by a single layer of benign cuboidal CD34(+) , CD31(+) , D2-40(-) endothelial cells, separated by loose stroma with spindle cells. One tumour was a cellular capillary haemangioma. Intravascular growth was seen in nine specimens. All haemangiomas had extramedullary haematopoiesis. Acquired cystic kidney disease (ACKD) was seen in 11 kidneys (nine patients), renal cell carcinoma (RCC) in five, ACKD-associated RCC precursors in three, Wilms' tumour in one and papillary adenomas in five. CONCLUSIONS: Anastomosing haemangioma appears as a distinctive clinicopathological entity developing in kidneys with ESRD, with or without ACKD.

Large, Hormonally Active Primary Cardiac Paraganglioma: Diagnosis and Management.

We describe a 26-year-old woman presenting with chest pain and evidence of coronary ischemia. Echocardiography revealed a large left ventricular mass initially deemed unresectable at her initial institution. Investigation revealed a dopamine-secreting primary cardiac paraganglioma encompassing vital cardiac architecture. This case discusses our heart team approach to complex cardiac masses and illustrates the feasibility of surgical resection in complex cases of hormonally active primary cardiac paragangliomas.

Atypical Presentation of Right Ventricular Cardiac Hamartoma in a Young Man.

Cardiac tumors in adults are exceedingly rare and usually benign. We describe a 29-year-old man with a previous diagnosis of interventricular septal hypertrophy who presented with increasing severity of dyspnea and fatigue. Work-up revealed a 4.9 × 3.7 cm mass at the base of the interventricular septum. Biopsy revealed a benign cardiac hamartoma atypically located in the right ventricle, and the mass was resected via right ventriculotomy.

A Phase 2 Trial of Enhancing Immune Checkpoint Blockade by Stereotactic Radiation and In Situ Virus Gene Therapy in Metastatic Triple-Negative Breast Cancer.

PURPOSE: A Phase 2 trial of stereotactic radiotherapy and in situ cytotoxic virus therapy in patients with metastatic triple-negative breast cancer (mTNBC) followed by pembrolizumab (STOMP) was designed to evaluate dual approach of enhancing single-agent immune checkpoint blockade with adenovirus-mediated expression of herpes-simplex-virus thymidine-kinase (ADV/HSV-tk) plus valacyclovir gene therapy and stereotactic body radiotherapy (SBRT) in patients with mTNBC. PATIENTS AND METHODS: In this single-arm, open-label Phase 2 trial, patients with mTNBC were treated with ADV/HSV-tk [5 × 1011 virus particles (vp)] intratumoral injection, followed by SBRT to the injected tumor site, then pembrolizumab (200 mg, every 3 weeks). The primary endpoint was clinical benefit rate [CBR; complete response (CR), partial response (PR), or stable disease (SD) ≥ 24 weeks per RECIST version1.1 at non-irradiated site]. Secondary endpoints included duration on treatment (DoT), overall survival (OS), and safety. Exploratory endpoints included immune response to treatment assessed by correlative tissue and blood-based biomarkers. RESULTS: Twenty-eight patients were enrolled and treated. CBR was seen in 6 patients (21.4%), including 2 CR (7.1%), 1 PR (3.6%), and 3 SD (10.7%). Patients with clinical benefit had durable responses, with median DoT of 9.6 months and OS of 14.7 months. The median OS was 6.6 months in the total population. The combination was well tolerated. Correlative studies with Cytometry by Time of Flight (CyTOF) and imaging mass cytometry (IMC) revealed a significant increase of CD8 T cells in responders and of myeloid cells in non-responders. CONCLUSIONS: The median OS increased by more than 2-fold in patients with clinical benefit. The therapy is a well-tolerated treatment in heavily pretreated patients with mTNBC. Early detection of increased effector and effector memory CD8 T cells and myeloids correlate with response and non-response, respectively.

The immunohistochemical profile of atypical eosinophilic syncytial changes vs serous carcinoma.

Endometrial epithelial cytoplasmic change (EECC) is an adaptive cytoplasmic change commonly seen in the endometrium. Previously considered "metaplasia," EECC is now the preferred term because it offers a descriptive designation without implying a specific mechanism of development. There are 5 types of EECC: squamous, ciliated cell, eosinophilic, mucinous, and secretory (clear cell and hobmail cell) changes. Eosinophilic syncytial change (ESC) is a similar but unrelated degenerative change seen in endometrial breakdown. Some cases of ESC show atypical cytologic features that may resemble endometrial adenocarcinoma. Thirteen endometrial biopsy and curettage specimens with atypical ESCs (AESCs) were compared against 10 hysterectomy specimens with endometrial serous carcinoma. Clinical information and immunohistochemical staining profiles for markers phosphatase and tensin homologue deleted on chromosome 10 (PTEN), p53, and Ki-67 were evaluated in each case. All 13 cases of AESC (100%) showed moderate-to-strong staining for PTEN, whereas PTEN expression was absent in all endometrial serous carcinomas (P < .001). Seven cases of AESC (54%) showed focal, weak positivity for p53, whereas all cases of serous carcinoma (100%) showed strong staining (P < .001). The Ki-67 index was low (3%-15%) and found in only 3 cases in AESC (32%) but was high (60%-90%) in all cases of endometrial serous carcinoma (100%) (P < .001). Atypical ESC and serous carcinoma share several morphological features on hematoxylin and eosin-stained sections that may complicate accurate diagnosis. The PTEN, p53, and Ki-67 staining profile can effectively distinguish between AESC and malignancy in difficult cases, providing an invaluable tool for a challenging diagnostic dilemma.

Spinal Anesthesia in 2 Consecutive Cesarean Deliveries in a Parturient With Type 3 von Willebrand Disease: A Case Report.

Type 3 von Willebrand disease is a rare and severe inherited bleeding disorder that carries an elevated risk for epidural and spinal hematoma as well as pregnancy-associated complications. Neuraxial anesthesia in these patients is controversial but may be considered if the parturient has received appropriate factor replacement. We present the case of a woman with type 3 von Willebrand disease and a severe bleeding history that underwent successful spinal anesthesia during successive cesarean deliveries. Our case highlights the importance of early multidisciplinary consultation and advance planning in the care of these rare events.