Cardiac atrial pathology in Duchenne muscular dystrophy.

INTRODUCTION/AIMS: Duchenne muscular dystrophy (DMD) is characterized by fibrofatty replacement of muscle. This has been documented in the ventricular myocardium of DMD patients, but there is limited description of atrial involvement. The purpose of this study is to examine the arrhythmia and ectopy burden in patients with DMD and non-DMD dilated cardiomyopathy (DCM) and to characterize the cardiac histopathologic changes in DMD patients across the disease spectrum. METHODS: This was a retrospective analysis of age-matched patients with DMD and non-DMD DCM who received a Holter monitor and cardiac imaging within 100 days of each other between 2010 and 2020. Twenty-four-hour Holter monitors were classified based on the most recent left ventricular ejection fraction at the time of monitoring. Cardiac histopathologic specimens from whole-heart examinations at the time of autopsy from three DMD patients and one DCM patient were reviewed. RESULTS: A total of 367 patients with 1299 Holter monitor recordings were included over the study period, with 94% representing DMD patients and 6% non-DMD DCM. Patients with DMD had more atrial ectopy across the cardiac function spectrum (p < 0.05). There was no difference in ventricular ectopy. Four DMD patients developed symptomatic atrial arrhythmias. Autopsy specimens from DMD patients demonstrated fibrofatty infiltration of both atrial and ventricular myocardium. DISCUSSION: The atrial myocardium in patients with DMD is unique. Autopsy specimens reveal fibofatty replacement of the atrial myocardium, which may be a nidus for both ectopy and arrhythmias in DMD patients.

Delayed hemorrhagic gastritis caused by immunotherapy in a patient With metastatic melanoma.

Pembrolizumab is a monoclonal antibody which targets the programmed cell death protein 1 (PD-1) receptor of lymphocytes. It is commonly used to treat many types of malignancies. Immunotherapy-related adverse events are relatively common and include pneumonitis, colitis and hepatitis. A rare side effect of immunotherapy is gastrointestinal (GI) bleeding secondary to hemorrhagic gastritis. Side effects from immunotherapy most commonly occur eight to twelve weeks after initiation of therapy but can vary from days after the first dose to even months later. We present a rare case of a patient with metastatic melanoma who had confirmed immune-mediated hemorrhagic gastritis which occurred after 23 cycles of Pembrolizumab. Biopsies for Heliobacter Pylori (H. pylori) and cytomegalovirus (CMV) were negative. The patient's immunotherapy was discontinued, and he was started on high dose steroids. The symptoms (nausea, vomiting, and abdominal pain) improved dramatically with a long steroid taper. An esophagogastroduodenoscopy (EGD) performed three months after hospital discharge showed improvement in gastric mucosa, but biopsies continued to show evidence of acute and chronic gastritis. As cancer patients continue to live longer with immunotherapy, it is important for all providers to be aware of the less common side effects of newer agents such as pembrolizumab.

Primary monophasic breast synovial sarcoma in a female patient.

Synovial sarcoma (SS) is a rare soft tissue sarcoma usually arising in the deep soft tissues of the limbs, trunk, and head and neck region. Due to its rarity, diagnosis can be difficult to establish, especially when it involves an uncommon location like the breast. In this case report, we describe a young woman who was found to have primary SS of the breast. Initial immunohistochemistry staining was focally positive for cytokeratin and S100 and she was misdiagnosed with atypical spindle cell carcinoma. Due to the unusual presentation, further testing was performed which showed TLE1 and epithelial membrane antigen positivity, establishing the diagnosis of SS of the breast. A FISH was later sent out and was positive for SS18-SSX fusion transcript. This case highlights the importance of considering rare histopathology in breast lesions and using additional staining and cytogenetics to confirm diagnosis.

Goblet Cell Adenocarcinoma With Heterotopic Ossification: A Rare Case Report and Review of Literature.

Heterotopic bone formation is a rare phenomenon when associated with gastrointestinal neoplasms. Here we present a rare case of heterotopic ossification associated with goblet cell adenocarcinoma of the appendix, and a literature review of such cases associated with neoplasms within and out of the gastrointestinal tracts. We reviewed the clinical data and when available, immunohistochemical markers of osteoblastic differentiation. Our review shows similar findings to prior reports of apparent high association of heterotopic bone formation with neoplasms with mucinous features. Two, previously proposed main hypotheses of the mechanisms are reviewed. The unique feature about this case is that goblet cell adenocarcinoma was not reported previously in the setting of bone formation.

Risk stratification of ER-positive breast cancer patients: A multi-institutional validation and outcome study of the Rochester Modified Magee algorithm (RoMMa) and prediction of an Oncotype DX® recurrence score <26.

The skyrocketing cost of health-care demands that we question when to use multigene assay testing in the planning of treatment for breast cancer patients. A previously published algorithmic model gave recommendations for which cases to send out for Oncotype DX® (ODX) testing. This study is a multi-institutional validation of that algorithmic model in 620 additional estrogen receptor positive breast cancer cases, with outcome data on 310 cases, named in this study as the Rochester Modified Magee algorithm (RoMMa). RoMMa correctly predicted 85% (140/164) and 100% (17/17) of cases to have a low- or high-risk ODX recurrence score, respectively, consistent with the original publication. Applying our own risk stratification criteria, in patients who received appropriate hormonal therapy, only one of the 45 (2.0%) patients classified as low risk by our original algorithm have been associated with a breast cancer recurrence over 5-10 years of follow-up. Eight of 116 (7.0%) patients classified as low risk by ODX have been associated with a breast cancer recurrence with up to 11 years of follow-up. In addition, 524 of 537 (98%) cases from our total population (n = 903) with an average modified Magee score ≤18 had an ODX recurrence score <26. Patients with an average modified Magee score ≤18 or >30 may not need to be sent out for ODX testing. By avoiding these cases sending out for ODX testing, the potential cost savings to the health-care system in 2018 are estimated to have been over $100,000,000.

Impact of 21-Gene Expression Assay on Staging Estrogen Receptor-Positive HER2-Negative Breast Cancer.

PURPOSE: The 8th edition of the American Joint Committee on Cancer (AJCC) breast cancer staging system requires histologic grade (GR), estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and stage (assessed by the tumor, node, metastasis classification system). For T1-2 N0, ER+/HER2- tumors, if the 21-gene expression assay is ordered and Oncotype DX (ODX) recurrence score (RS) is 0 to 10, the stage is IA. The purpose of this study was to determine the impact of the ODXRS on staging ER+/HER2- tumors. MATERIALS AND METHODS: This is a retrospective review of ER+/HER2- invasive breast cancer (BC) with ODXRS results from 2 institutions (n = 816) between 2006 and 2018. Stage based on the AJCC 7th and 8th editions, and stage using the 8th edition with and without ODXRS were compared. Significant associations among pathologic parameters and ODX risk groups were determined. Clinical histories were reviewed. RESULTS: Nearly half of the patients (43%) had a change in BC stage using the new staging system. Only 4 patients changed stage as a direct result of ODXRS. Influence of ODXRS on staging is limited to T2N0 tumors that are either GR 3 and strongly ER+ and PR+ or GR 1-2 and ER+/PR-. Sixty-one percent of cases of recurrence (11/18) were downstaged using the new staging system. CONCLUSION: ODXRS has little influence on staging, thus supporting the view of the AJCC 8th edition expert panel that ODX is not required for staging. Downstaging of more than half of cases of recurrence suggests that continued refinement of the staging system, as proposed by the expert panel, could be beneficial in this subgroup of patients.

Disseminated Nocardiosis with retinal abscess in a patient treated for bullous pemphigoid.

PURPOSE: To report a case of disseminated Nocardiosis with retinal and intracranial lesions. OBSERVATIONS: A 49-year-old woman immunosuppressed because of treatment given for bullous pemphigoid presented with altered mental status and multiple intracranial lesions on imaging. The patient was found to have multiple retinal lesions in both eyes, including a subretinal abscess in the right eye. The patient underwent brain biopsy, confirming Nocardia farcinica histopathologically and in culture. CONCLUSIONS AND IMPORTANCE: Ocular Nocardiosis is a rare disease with varying prognosis that requires prompt diagnosis to ensure appropriate medical therapy.