Coexistent Dedifferentiated Endometrioid Carcinoma of the Uterus and Adenocarcinoma of the Bladder in Lynch Syndrome: Case Report and Review of the Literature.

Lynch syndrome is an autosomal dominant disorder, caused by an abnormality in DNA mismatch repair genes and characterized by the development of a variety of cancers. Upper urinary tract urothelial carcinoma is well characterized in Lynch syndrome; however, support for the inclusion of bladder urothelial carcinoma is limited, except for MSH2 mutation carriers. Urologic adenocarcinoma has not been documented in Lynch syndrome. Here we report, to the best of our knowledge, the first case of bladder adenocarcinoma, synchronous with uterine endometrioid dedifferentiated endometrioid adenocarcinoma in a patient with Lynch syndrome. We present a 47-year-old woman with an MLH1 gene mutation (G133X 397G>T) who presented with menorrhagia. Eleven family members have this mutation, 6 with carcinoma: 5 colorectal and 1 with a gynecologic primary of unknown type. Colonoscopy and endoscopy were unremarkable. Positron emission and computed tomography revealed a 3 cm anterior dome bladder mass without additional extrauterine disease or uterine connection. She underwent partial cystectomy, laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and lymphadenectomy. The uterus demonstrated a dedifferentiated endometrioid adenocarcinoma, immunohistochemically positive for vimentin, ER, CK7, MSH2, MSH6, and p53 (focally) and negative for CEA, CDX2, CK20, ß-catenin, MLH1, and PMS2. The bladder demonstrated a well-differentiated, enteric-type adenocarcinoma without muscularis propria invasion, positive for CEA, CDX2, CK20, p53, MSH2, and MSH6 and negative for vimentin, ER, CK7, MLH1, and PMS2. Eleven nodes were negative for carcinoma. The morphologic, immunohistochemical, and clinical findings support synchronous bladder adenocarcinoma, enteric type, and uterine dedifferentiated endometrioid adenocarcinoma, in a patient with Lynch syndrome.

Next generation sequencing of cervical high grade dysplasia and invasive squamous cell carcinoma: A case study.

Cervical cancer continues to be a prevalent diagnosis among gynecologic pathology despite widespread screening methods and known pathogenesis by human papilloma virus. We describe a patient who underwent next generation sequencing (NGS) of her high grade squamous dysplasia (HG-SIL) as well as the invasive component of her cervical cancer. This tumor showed an amplification of PIK3CA in the invasive carcinoma in addition to a common E542K mutation both in dysplastic and invasive carcinoma. The dysplasia also showed a novel PCNX (e1) - RAD51B (e8) fusion suggesting potentially new mechanisms of pathogenesis in cervical squamous cell carcinoma.

A rare case of acral amelanotic melanoma, nodular type.

Amelanotic melanoma is a rare melanoma subtype, and it is even more rare when it occurs at an acral site. We here present a case of a nodular amelanotic acral melanoma (NAAM) occurring on the heel of an 83-year old female. It presented as an ulcerated pink nodular growth on the heel, which clinically mimicked other nodular non-pigmented lesions, causing a delay in diagnosis until it was biopsied. This case is a demonstration of the critical importance to include NAAM in the differential diagnosis of nodular non-pigmented skin lesions as to avoid delay in diagnosis and disease progression, in which early detection can provide the most modifiable prognostic factor.

Myxoid-round cell liposarcoma: MRI appearance after radiation therapy and relationship to response.

Liposarcomas are classified into 4 different subtypes, with the myxoid-round cell variant demonstrating increased morbidity and metastatic potential dependent on cell composition. Unique to sarcomas, the myxoid-round cell liposarcoma is remarkably sensitive to radiation therapy in the pretreatment setting, owing to the tumor morphology and vascular distribution. Herein we report a case of myxoid-round cell liposarcoma within the deep soft tissues of the thigh of an 81-year-old male with excellent neoadjuvant response to radiation. We briefly review treatment options.

Ductal Spread Versus High-Grade Prostatic Intraepithelial Neoplasia: A Diagnostic Pitfall.

Ductal spread (DS) of acinar adenocarcinoma of the prostate can lead to an incomplete replacement of the benign epithelium by cancer cells, resulting in a lesion that can be indistinguishable from high-grade prostatic intraepithelial neoplasia (HGPIN). Kovi and colleagues demonstrated 30 years ago that there is a significant association between the presence of DS and local extent of invasive adenocarcinoma, making the distinction between DS and HGPIN clinically relevant. However, despite the existence of certain morphologic features that are suggestive of DS, a definitive differentiation between the aforementioned lesions cannot always be attained.

Synchronous Ipsilateral Parotid Tumors with Cytologic-Histologic Correlation.

Synchronous ipsilateral tumor formation within a major salivary gland is a very rare event. In this case, a 54-year-old female tobacco smoker presented with a slowly enlarging left parotid gland. Computed tomography of the neck demonstrated a solid mass superficial to a cystic mass in the deep lobe of the gland. Ultrasound-guided fine needle aspiration yielded oncocytic cells, lymphoid cells, and granular debris along with rare cohesive groups of basaloid cells. Parotidectomy was performed, and the resected gland was found to contain two adjacent but distinct masses. One mass, a predominantly solid, well-circumscribed lesion composed of ribbons of double-layered oncocytic cells and a lymphoid stroma with germinal center formation, was a Warthin tumor. The other mass, a predominantly cystic lesion composed of cords and nests of basaloid cells with associated deposits of basement membrane-like material, was a basal cell adenoma of the membranous type. To our knowledge, this is the first reported case of synchronous Warthin tumor and basal cell adenoma of the parotid gland with cytologic-histologic correlation attributable to each tumor.

Coexistent Isolated Tumor Cell Clusters of Infiltrating Lobular Carcinoma and Benign Glandular Inclusions of Müllerian (Endosalpingiosis) Type in an Axillary Sentinel Node: Case Report and Review of the Literature.

The presence of benign epithelial inclusions in axillary lymph nodes coexistant with breast disease is a rare event; however, their presence makes the assessment of nodal disease diagnostically challenging. Broadly, these inclusions can be classified as glandular (müllerian type or nonmüllerian type), mixed glandular-squamous, and squamous. Among these the presence of benign müllerian-type glandular inclusions with concurrent breast parenchymal disease is an exceedingly rare event, with 10 previous cases reported in the literature, 2 coexisting with infiltrating ductal-type mammary carcinoma in axillary lymph nodes. Here, we report the first case of coexistent invasive lobular carcinoma and endosalpingiosis in an axillary lymph node.

Gene expression in hepatocellular carcinoma: pilot study of potential transarterial chemoembolization response biomarkers.

PURPOSE: To perform a feasibility study to explore the relationship between hepatocellular carcinoma genetics and transarterial chemoembolization treatment response to identify potential biomarkers associated with enhanced treatment efficacy. MATERIALS AND METHODS: In this single-institution study, pretreatment hepatocellular carcinoma biopsy specimens for tumors in 19 patients (14 men, five women; mean age, 59 y) treated with chemoembolization between 2007 and 2013 were analyzed for a panel of 60 chemotherapy-sensitivity, hypoxia, mitosis, and inflammatory genes with the QuantiGene Plex 2.0 mRNA detection assay. Demographic, disease, and procedure data and tumor response outcomes were collected. Quantitative mRNA levels were compared based on radiologic response between tumors exhibiting complete response (CR) versus partial response (PR). RESULTS: The study sample included 19 biopsy specimens from tumors (mean size, 3.0 cm; grade 1, n = 6; grade 2, n = 9; grade 3, n = 4) in patients treated with a mean of two conventional chemoembolization sessions. Thirteen and six tumors exhibited CR and PR, respectively, at a mean of 116 days after treatment. Tumors with CR showed a significant increase in (P < .05) or trend toward (P < .1) greater (range, 1.49-3.50 fold) pretreatment chemotherapy-sensitivity and mitosis (ATF4, BAX, CCNE1, KIF11, NFX1, PPP3CA, SNX1, TOP2A, and TOP2B) gene mRNA expression compared with tumors with PR, in addition to lower CXCL10 levels (0.48-fold), and had significantly (P < .05) higher (1.65-fold) baseline VEGFA levels. CONCLUSIONS: Genetic signatures may allow prechemoembolization stratification of tumor response probability, and gene analysis may therefore offer an opportunity to personalize locoregional therapy by enhancing treatment modality allocation. Further corroboration of identified markers and exploration of their respective predictive capacity thresholds is necessary.

Mechanistic insights and characterization of sickle cell disease-associated cardiomyopathy.

BACKGROUND: Cardiovascular disease is an important cause of morbidity and mortality in sickle cell disease (SCD). We sought to characterize sickle cell cardiomyopathy using multimodality noninvasive cardiovascular testing and identify potential causative mechanisms. METHODS AND RESULTS: Stable adults with SCD (n=38) and healthy controls (n=13) prospectively underwent same day multiparametric cardiovascular magnetic resonance (cine, T2* iron, vasodilator first pass myocardial perfusion, and late gadolinium enhancement imaging), transthoracic echocardiography, and applanation tonometry. Compared with controls, patients with SCD had severe dilation of the left ventricle (124±27 vs 79±12 mL/m(2)), right ventricle (127±28 vs 83±14 mL/m(2)), left atrium (65±16 vs 41±9 mL/m(2)), and right atrium (78±17 vs 56±17 mL/m(2); P<0.01 for all). Patients with SCD also had a 21% lower myocardial perfusion reserve index than control subjects (1.47±0.34 vs 1.87±0.37; P=0.034). A significant subset of patients with SCD (25%) had evidence of late gadolinium enhancement, whereas only 1 patient had evidence of myocardial iron overload. Diastolic dysfunction was present in 26% of patients with SCD compared with 8% in controls. Estimated filling pressures (E/e', 9.3±2.7 vs 7.3±2.0; P=0.0288) were higher in patients with SCD. Left ventricular dilation and the presence of late gadolinium enhancement were inversely correlated to hepatic T2* times (ie, hepatic iron overload because of frequent blood transfusions; P<0.05 for both), whereas diastolic dysfunction and increased filling pressures were correlated to aortic stiffness (augmentation pressure and index, P<0.05 for all). CONCLUSIONS: Sickle cell cardiomyopathy is characterized by 4-chamber dilation and in some patients myocardial fibrosis, abnormal perfusion reserve, diastolic dysfunction, and only rarely myocardial iron overload. Left ventricular dilation and myocardial fibrosis are associated with increased blood transfusion requirements, whereas left ventricular diastolic dysfunction is predominantly correlated with increased aortic stiffness. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01044901.

Palpitations in a 64-year-old man.

A 64-year-old man presented with several weeks of intermittent irregular palpitations. He had no prior history of cardiac disease, hypertension or syncope. A 12-lead ECG revealed sinus rhythm with premature atrial and ventricular contractions and high QRS voltages consistent with LV-hypertrophy. Cardiac MR revealed asymmetrical septal hypertrophy and marked mid-myocardial hyperenhancement of the interventricular septum.

Genital ulcers associated with Epstein-Barr virus.

Genital ulcerations are a rare clinical finding of Epstein-Barr virus (EBV) infection. We present the case of a 16-year-old adolescent girl who reported the onset of diarrhea, headaches, dysuria, and vaginal discharge along with vulvar ulcerations with edema. Laboratory studies revealed a high-quantitative EBV IgG and early antigen as well as a positive IgM antibody for EBV. Although the association between EBV and genital ulcerations is rare, physicians should be aware of this clinical presentation to exclude other infectious entities, to be reassured to accept negative testing, and to quell patient distress or concerns of abuse.