Melanie C. Bois

Benign lipomatous masses of the heart: a comprehensive series of 47 cases with cytogenetic evaluation ☆

Benign lipomatous lesions of the heart encompass an apparently etiologically diverse group of entities including neoplastic, congenital, and reparative phenomena. Among these, lipomas and lipomatous hypertrophy of the atrial septum (LHAS) represent 2 commonly encountered mass lesions. To date, no study has systematically and comparatively evaluated the morphologic and genetic characteristics of these lesions. Tissue registry archives of Mayo Clinic were queried for cases of cardiac lipoma and LHAS (1994-2011). Clinical, imaging, and pathologic findings were reviewed. Representative cases in each cohort were evaluated by fluorescence in situ hybridization (FISH) for HMGA1 and HMGA2 loci rearrangement and for MDM2/CPM locus amplification. Five cases of cardiac lipoma were identified (mean age, 67 years; range, 48-101; 3 men): 4 right atrial and 1 left ventricular. Forty-two cases of LHAS were identified (mean age, 75.6 years; range 45-95; 20 men), 39 of which were autopsy derived. The median size was 3.4 cm for lipomas and 2.8 cm for LHAS (n = 14). A single case each of cardiac lipoma and LHAS were found to harbor HMGA2 rearrangement, whereas no case showed cytogenetic abnormality of HMGA1 or CPM. This represents the largest series of histopathologically confirmed cardiac lipomas from a single institution. In addition, it is the first to evaluate cardiac lipomas and LHAS for genetic alterations associated with extracardiac lipomatous lesions. The genetic and morphologic similarities found provide evidence in support of the neoplastic classification of cardiac lipomas. A single case of LHAS contained an HMGA2 rearrangement, challenging the currently accepted hypothesis of pathogenesis for this lesion.

ERβ Expression and Breast Cancer Risk Prediction for Women with Atypias

Estrogen receptor (ER) β is highly expressed in normal breast epithelium and a putative tumor suppressor. Atypical hyperplasia substantially increases breast cancer risk, but identification of biomarkers to further improve risk stratification is needed. We evaluated ERβ expression in breast tissues from women with atypical hyperplasia and association with subsequent breast cancer risk. ERβ expression was examined by immunohistochemistry in a well-characterized 171-women cohort with atypical hyperplasia diagnosed 1967–1991. Nuclear ERβ percent and intensity was scored in the atypia and adjacent normal lobules. An ERβ sum score (percent + intensity) was calculated and grouped as low, moderate, or high. Competing risks regression was used to assess associations of ERβ expression with breast cancer risk. After 15-year median follow-up, 36 women developed breast cancer. ERβ expression was lower in atypia lobules in than normal lobules, by percent staining and intensity (both P < 0.001). Higher ERβ expression in the atypia or normal lobules, evaluated by percent staining, intensity or sum score, decreased the risk of subsequent breast cancer by 2-fold (P = 0.04) and 2.5-fold (P = 0.006). High normal lobule ERβ expression conferred the strongest protective effect in premenopausal women: the 20-year cumulative incidence of breast cancer was 0% for women younger than 45 years with high versus 31% for low–moderate ERβ expression (P = 0.0008). High ERβ expression was associated with a significantly decreased risk of breast cancer in women with atypical hyperplasia. These data suggest that ERβ may be a useful biomarker for risk stratification and a novel therapeutic target for breast cancer risk reduction. Cancer Prev Res; 8(11); 1084–92. ©2015 AACR.

Increasing Pulmonary Infiltrates in a 72-Year-Old Woman With Metastatic Breast Cancer

Abstract A 71-year-old woman, nonsmoker, with a history of metastatic breast cancer was referred for evaluation of worsening pulmonary infiltrates. She described slowly increasing exertional dyspnea and cough in the preceding 3 months. Twenty-two years before, she had been diagnosed with invasive ductal carcinoma of the left breast, for which she underwent a left modified radical mastectomy and prophylactic right simple mastectomy and bilateral breast reconstruction using silicone implants. She subsequently underwent combination chemotherapy. She did well during the following 7 years until an enlarging liver lesion was noted that proved to be metastatic breast cancer, for which she underwent a right hepatectomy. Five years later, she developed intrathoracic and supraclavicular lymphadenopathy, a left pleural effusion, and cervical spine lesions. A biopsy specimen from a supraclavicular lymph node showed metastatic breast cancer, for which she started letrozole therapy with resolution of intrathoracic findings. Twelve months before presentation she underwent bilateral capsulectomy with silicone implant exchange because of pain from implant contracture. Her medications included letrozole, 2.5 mg once a day, and vitamin and Chinese herbal supplements. Her family history was positive for breast cancer in her maternal grandmother.

Could prominent airway-centered fibroblast foci in lung biopsies predict underlying chronic microaspiration in idiopathic pulmonary fibrosis patients? ☆

Chronic occult aspiration of small droplets (microaspiration) due to gastroesophageal reflux disease (GERD) and/or hiatal hernia is postulated to be a contributing factor in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Usual interstitial pneumonia (UIP) is the histopathologic correlate of IPF. We hypothesized that chronic microaspiration may manifest as prominent airway-centered fibroblastic foci (FFs) in IPF. UIP cases diagnosed by wedge biopsies over a 6-year period (2006-2011) were identified and scored (1-3) for the prominence of airway-centered FFs by 2 authors blinded for clinical history. Relevant clinical information was obtained. Thirty-seven patients (22 men) were diagnosed with IPF by multidisciplinary approach. Thirteen cases (35.1%) demonstrated high airway-centered FF score (score 3). Twenty (54.1%) patients carried a clinical diagnosis of GERD, and 3 patients (8.1%) had hiatal hernia. High airway-centered FF score was significantly associated with hiatal hernia diagnosis (P=.037) but not with a diagnosis of GERD or the use of proton pump inhibitors/histamine-2 receptor antagonists. High airway-centered FF score was associated with airway-centered acute inflammation (P=.028) and peribronchiolar granulomas (P=.042). In summary, IPF cases with hiatal hernia were more likely to have a prominent airway-centered FF. Given the strong association between hiatal hernia and GERD and their risk for developing chronic microaspiration, the prominent airway-centered FF in UIP might predict the presence of chronic microaspiration, acknowledging that GERD and proton pump inhibitor/histamine-2 receptor antagonist use failed to demonstrate a significant association. Larger studies are warranted for further investigation.

Healed Fracture of Superior Horn of Thyroid Cartilage in Autoerotic Asphyxia: An Indication of Prior Activity? A Case Report Utilizing 3D Scanning and Printing of the Larynx

Evidence of prior autoerotic asphyxia is often difficult to establish due to the decedents efforts to hide the activity from others. In this case report, we suggest that a healed fracture of the thyroid cartilage is indicative of prior autoerotic asphyxia activity. The decedent was a 45-year-old man who was found unclothed on the floor of his bedroom with a belt ligature around the neck. A second rope ligature was loosely wrapped around the decedents wrists, scrotum, and penis. A definitive escape mechanism was not identified, but a nearby towel and barbell weight may have comprised a possible escape mechanism. There was no known history of depression or prior autoerotic activity. Autopsy was notable for the presence of a healed fracture of the right superior horn of the thyroid cartilage. Three-dimensional (3D) surface scanning and 3D printing was utilized to preserve the anatomical findings prior to histologic sampling. To our knowledge, this is the first reported use of 3D surface scanning and 3D printing for the purpose of documenting a forensic finding prior to alteration of the anatomical specimen for histologic sampling. Acute fractures of the superior horns of the thyroid cartilage are not infrequently seen in ligature hanging. Therefore, the presence of a healed fracture in the setting of autoerotic asphyxia likely indicates prior activity. Histologic sampling of the laryngeal cartilages to detect occult healed fractures in autoerotic asphyxia may be useful. Three-dimensional scanning and printing may alleviate concerns for specimen alteration due to histology sampling.

Percutaneous transcatheter biopsy for intracardiac mass diagnosis

AIMS The differential diagnosis of intracardiac masses (ICM) is wide. While imaging modalities can suggest a diagnosis, clinical decision making usually requires histopathologic diagnosis. The aim of this study was to describe the procedural technique, safety outcomes, diagnostic accuracy and clinical utility of percutaneous transcatheter biopsy (TCB) for histopathologic diagnosis of ICM. The records of all patients undergoing TCB of ICM at the Mayo Clinic catheterisation laboratories in Rochester, Minnesota, between 2002 and 2017 were retrieved and reviewed. METHODS AND RESULTS TCB of ICM to establish histopathologic diagnosis was performed in 29 patients. Masses were located in the right-sided chambers in 93% of cases. Echocardiographic guidance was used. Ventricular arrhythmias requiring immediate cardioversion occurred in 7% of patients. No other complications were noted. The average number of samples retrieved per procedure was 7±3.6. A histopathologic diagnosis was made by TCB in 72% and altered clinical decision making in 52% of patients overall. Eleven patients (38%) who would otherwise have required excisional biopsy were able to avoid cardiovascular surgery. Each additional biopsy sample was associated with an increase in the likelihood of making a histopathologic diagnosis (OR 1.74, 95% CI: 1.05-2.87, p=0.032). CONCLUSIONS Echo-guided percutaneous TCB of ICM provides an accurate diagnosis and alters clinical management in the majority of cases. The procedural complication rate is low. An increase in the number of samples retrieved markedly improves the ability to render a diagnosis. TCB may therefore be considered as a first-line approach for the histopathologic diagnosis of ICM.

Neoplastic embolization to systemic and pulmonary arteries

Objective: Arterial neoplastic emboli are uncommon, accounting for <1% of thromboemboli in the current literature. Nonetheless, this event may be associated with significant morbidity and mortality. Herein, we report a series of 11 cases of arterial neoplastic emboli from a single tertiary care center along with a comprehensive review of the literature to date. The aim of this study was to document the incidence, clinical presentations, and complications of arterial neoplastic emboli as well as to highlight the importance of routine histologic examination of thrombectomy specimens. Methods: Pathology archives from a single tertiary care institution were queried to identify cases of surgically resected arterial emboli containing neoplasm (1998‐2014). Histopathology was reviewed for confirmation of diagnosis. Patient demographics and oncologic history were abstracted from the medical record. Comprehensive literature review documented 332 patients in 275 reports (1930‐2016). Results: Eleven patients (six men) with a median age of 63 years (interquartile range, 42‐71 years) were identified through institutional archives. Embolism was the primary form of diagnosis in seven (64%) cases. Cardiac involvement (primary or metastasis) was present in more than half of the cohort. Comprehensive literature review revealed that pulmonary primaries were the most common anatomic origin of arterial neoplastic emboli, followed by gastrointestinal neoplasia. Cardiac involvement was present in 18% of patients, and sentinel identification of neoplasia occurred in 30% of cases. Postmortem evaluation was the primary means of diagnosis in 27%. Conclusions: This study highlights the importance of routine histopathologic evaluation of embolectomy specimens in patients with and without documented neoplasia.

Hydroxychloroquine-Mediated Cardiotoxicity With a False-Positive 99m Technetium–Labeled Pyrophosphate Scan for Transthyretin-Related Cardiac Amyloidosis

Cardiac amyloidosis is a rare infiltrative process most commonly caused by abnormal deposition of precursor proteins from monoclonal light chain or transthyretin (ATTR).1 An accurate diagnosis of the amyloidosis subtype has crucial prognostic and therapeutic implications. Bone scintigraphy using 99mtechnetium-labeled pyrophosphate (99mTc-PYP) has been found to have a sensitivity and specificity of 68% and 100%, respectively, for ATTR in patients without evidence of plasma cell dyscrasia.2 Furthermore, high heart/contralateral ratio of ≥1.6 predicted worse survival.3 This has led to a proposed nonbiopsy diagnosis of ATTR using bone scintigraphy.2 However, without widely using 99mTc-PYP scan in various cardiac conditions, the true specificity for …

Morphometric study of pulmonary arterial changes in pulmonary langerhans cell histiocytosis

CONTEXT - Pulmonary hypertension (PHT) is a complication of pulmonary Langerhans cell histiocytosis (PLCH); however, the pathogenesis remains largely unknown. Few studies have evaluated histopathologic changes in pulmonary arteries (PAs) of patients with PLCH; systematic quantification of arterial remodeling has yet to be undertaken. OBJECTIVE - To quantify the extent of arterial remodeling among patients with PLCH through morphometry and to correlate these results with pertinent clinical parameters. DESIGN - Patients with PLCH were identified from institutional files (1995-2015) along with age-, sex-, and smoking status-matched controls. Morphometric analysis of intimal and medial thickness of small to medium PAs was performed in patients with PLCH (within PLCH lesions [lesional] and away from PLCH lesions [nonlesional]) and controls. Paired measures were compared with Wilcoxon signed rank tests. RESULTS - Twenty-five patients with PLCH (14 men: median age, 46 years; interquartile range, 37-55 years) and 25 controls were included. The lesional arteries of patients with PLCH demonstrated thicker PA intima and media than controls ( P < .001 and P < .001, respectively), as did PLCH nonlesional arteries compared to controls ( P < .001 and P < .001, respectively). The PA intima and media were thicker within the PLCH lesions than nonlesional arteries ( P = .02 and P = .002, respectively). Patients with PLCH-related PHT had a worse prognosis than those without PHT ( P = .04; hazard ratio, 4.5 [1.1, 22.2]). Echocardiography parameters including right atrial size ( P = .007), estimated right atrial pressure ( P = .01), and right ventricular systolic pressure ( P = .01) were inversely associated with survival. CONCLUSIONS - Our findings suggest that factors other than direct vascular obstruction or inflammatory cell infiltration contribute, at least in part, to the vascular remodeling in PLCH.

Apolipoprotein A-IV–Associated Cardiac Amyloidosis

Cardiac amyloidosis may be inherited or acquired, both forms resulting from deposition of insoluble, misfolded proteins in extracellular locations. To date, 11 amyloidogenic proteins have been documented in the heart [(1)][1]. Among the rarely encountered causes of cardiac amyloidosis is