Pediatric combined hepatocellular-cholangiocarcinoma (cHCC-CC) with neuroendocrine features: distinguishing genetic alterations detected by chromosomal microarray.

BACKGROUND: Liver tumors exhibiting hepatocellular, cholangiocarcinoma, and neuroendocrine features are extremely rare, with only five cases reported in the literature. CASE PRESENTATION: We present an unusual case of a combined hepatocellular-cholangiocarcinoma (cHCC-CC) with neuroendocrine features in a pediatric patient. A 16-year-old presented with abdominal pain and a 21.0 cm mass in the right hepatic lobe with extension into the left lobe. Histology showed a poorly differentiated tumor with a solid, tubuloglandular, and microcystic architecture. Immunohistochemistry results were negative for hepatic markers, positive for markers of biliary differentiation, and positive for neuroendocrine differentiation. The neoplasm was reviewed at several institutions with differing diagnoses. Single nucleotide polymorphism (SNP) chromosomal microarray (CMA) showed large deletions within chromosomes 6q and 13q in both the hepatocellular-like areas and the cholangiocarcinoma-like areas, with additional large deletions in the cholangiocarcinoma-like areas, supporting origin from hepatocellular carcinoma. The final diagnosis was a cHCC-CC with neuroendocrine features. CONCLUSIONS: Diagnosis of cHCC-CCs relies predominately on histomorphology, as per the 2018 International Consensus Group on the nomenclature of cHCC-CC. These findings in this case support that the pathological classification of these lesions be based on molecular data, which could better direct treatment. Further classification of cHCC-CCs and determination of their clinicopathological relevance will require more interobserver consistency and continued molecular profiling of these lesions.

Endomyocardial biopsy facilitates diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA): a case report.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare small vessel leukocytoclastic vasculitis that affects multiple organs and is often associated with anti-neutrophil cytoplasmic antibody (ANCA). EGPA presenting with cardiac involvement is often ANCA-negative, difficult to diagnose, and often fatal. The treatment and prognosis and can be quite different for other conditions included in the differential diagnosis. Imaging modalities have proven unreliable, and the skin is the most commonly biopsied site for histological diagnosis. CASE SUMMARY: We report a case of a 55-year-old Hispanic man who presented with a non-ST-elevated myocardial infarction, reduced ejection fraction heart failure, and hypereosinophilia. The patient's clinical history also included poorly controlled asthma and sinonasal polyps. Despite ANCA titers within the normal range and a skin biopsy lacking evidence of EPGA, high clinical suspicion prompted an endomyocardial biopsy on day nine from hospital admission which facilitated the diagnosis of ANCA-negative EGPA-induced cardiomyopathy. Six months of follow-up revealed that therapeutic response, as measured by the cardiac ejection fraction, directly correlated with medication compliance. CONCLUSION: Endomyocardial biopsy aids in the diagnosis of EGPA and initiates use of appropriate therapy.

Aggressive Langerhans cell histiocytosis following T-cell acute lymphoblastic leukemia.

A 4-year-old female child developed cutaneous Langerhans cell histiocytosis 6 months following a diagnosis of T-cell acute lymphoblastic leukemia. Imaging revealed no evidence of systemic disease. Seven months later, the first systemic lesion was discovered on laryngoscopy. Restaging Positron Emission Tomography - Computed Tomography at that time revealed new 18-fluorodeoxyglucose-positive lesions in the left apical pleural margin, right lower peri-esophageal region, left ventricular myocardium, pancreas, upper pole of the left kidney, and inguinal and gluteal regions consistent with progressive systemic disease. Genomic testing revealed a low tumor mutational burden as well as mutations in KRAS G12A, ARID1A Q524, CDKN2A/B loss, and an alteration in NOTCH1.

Pulmonary Adenocarcinoma Presenting as a Pineal Gland Mass With Obstructive Hydrocephalus.

Background: Adenocarcinoma is the most prevalent type of non-small cell carcinoma of the lungs. Patients with lung adenocarcinoma often present with cough, dyspnea, pain, and weight loss. They can also present with signs and symptoms of brain metastasis because the lungs are one of the most common origins of metastatic brain cancer. We describe a rare case of adenocarcinoma of the lungs presenting with pineal region metastasis. Case Report: A 61-year-old male presented to the emergency department with dizzy spells and gait disturbance. Magnetic resonance imaging of the brain demonstrated a solitary mass in the pineal region with marked obstructive hydrocephalus. A stereotactic biopsy was performed, and metastatic adenocarcinoma consistent with pulmonary origin was diagnosed. Computed tomography scan of the chest revealed a spiculated mass. The patient died shortly after the diagnosis was made. Conclusion: The pineal region is an unusual site for brain metastasis. Although such metastasis has rarely been described, it should be considered in the differential diagnosis of pineal region tumors, especially for patients with suggestive clinical or histopathologic features of primary malignancy elsewhere.

Utility of Endoscopic Ultrasound in the Work Up for Solitary Hepatobiliary Neuroendocrine Lesions.

A 43-year-old woman, with an unremarkable past medical history, presented with a three-week history of generalized itching, jaundice, and abdominal pain. Initial workup showed amorphous, regionally invasive, and obstructing soft tissue mass in the region of the hepatic hilum. The middle third of the main bile duct was subsequently found to harbor a polypoid mass on endoscopic retrograde cholangiopancreatograph. Biopsy revealed nests of neoplastic cells that was subsequently identified as well-differentiated neuroendocrine tumor. A search for a possible primary neuroendocrine tumor was performed and included imaging of the chest, abdomen, and pelvis, a colonoscopy, capsule endoscopy, and an octreotide scan; however, no primary tumor outside of the liver was identified. Surgical debulking was performed, during which intraoperative exploration and ultrasound failed to reveal any extra-hepatic tumor sanctuaries. A few months later, patient underwent endoscopic ultrasound (EUS) for evaluation of recurrent abdominal pain which revealed a small lesion in the pancreas. It was unclear, however, whether it was primary or a metastatic lesion. This case represents a diagnostic challenge and emphasizes the potential utility of EUS in the preoperative work up for any presumable primary hepatobiliary neuroendocrine tumor.

Hypercalcaemia, renal dysfunction, anaemia and bone lesions (CRAB) do not always represent multiple myeloma: diffuse large B cell lymphoma presenting with CRAB symptoms in a 69-year-old man.

Hypercalcaemia, renal dysfunction, anaemia and bone lesions (CRAB) are a constellation of signs and symptoms that are collectively referred to as the CRAB features. When present together, multiple myeloma (MM) should be at the top of the differential diagnosis. We present a 69-year-old man who presented with severe body aches and bone pain in his ribs and pelvis, associated with fatigue and constipation. He was found to have hypercalcaemia, acute kidney injury, anaemia and numerous lytic lesion on chest imaging. Physical examination and imaging were unremarkable for any enlarged lymph nodes. The patient was initially suspected to have multiple myeloma, however, serum and urine protein electrophoresis, and serum free light chain assays were negative. The patient was ultimately diagnosed with diffuse large B cell lymphoma based on a bone marrow biopsy. This case highlights the fact that presence of hypercalcaemia, renal dysfunction, anaemia and bone lesions are not usually specific for MM.

The Sudden Development of Multi-Organ Lesions in a Patient With Pulmonary Sarcoidosis: A Case Report.

INTRODUCTION: Sarcoidosis is a systemic granulomatous inflammatory disease that can involve almost any organ system in the human body. It most frequently presents with pulmonary infiltrates, hilar lymphadenopathy, and skin lesions. Clinical and subclinical involvement of other organ systems is not uncommon. However, the simultaneous development of clinically apparent multisystem sarcoidosis is very rare. CASE DESCRIPTION: This 44-year-old Caucasian man presented to an outpatient clinic with a 2-month history of fatigue, night sweats, weight loss, loss of appetite, and mild abdominal discomfort. Initial laboratory finding showed elevated liver enzymes. Imaging studies revealed cirrhotic liver with steatosis, few enhancing hepatic masses, and multiple enlarged periaortic and portocaval lymph nodes. Liver biopsy revealed scattered necrotizing granulomatous hepatitis. Positron emission tomography scan showed extensive hepatic uptake, diffuse lymphadenopathy, as well as numerous fluorodeoxyglucose-avid osseous lesions. After extensive workup to rule out malignancy and infectious etiologies, a diagnosis of diffuse multi-organ sarcoidosis was made. He was ultimately treated with methotrexate and steroids, resulting in marked improvement in symptoms and liver function, with stable disease on repeat imaging. CONCLUSION: Diffuse multi-organ sarcoidosis is often associated with widespread lymphadenopathy and osseous lesions, which appear indistinguishable from malignancy on imaging. The angiotensin converting enzyme levels and inflammatory markers may be normal. Clinicians should be aware of the possibility of diffuse systemic sarcoidosis in any patient with a remote sarcoidosis history and the simultaneous development of multi-organ-related symptoms.

When Absence Seizures Are Not Seizure: A Case of Insulinoma.

Insulinomas are rare neuroendocrine tumors that produce excessive insulin and result in hypoglycemia. It can have a wide spectrum of symptoms and presentations which makes it difficult to diagnose at times. Here we present a 39-year-old woman who presented with intermittent diplopia, confusion, and staring episodes for one month. She had previously been seen by a neurologist who diagnosed her with possible absence seizures. However, evaluation showed that that patient had severe hypoglycaemia even with dextrose infusions. She was diagnosed with insulinoma based on lab work and a biopsy of a pancreatic tail mass. She underwent partial pancreatectomy, and has had a good outcome, with no recurrence of her symptoms. This case highlights the variable presentation of insulinomas, and the challenges faced with its diagnosis.