Faculty Bibliography

Erdheim-Chester disease (ECD) is a rare clonal histiocytic process that is characterized by a foamy (xanthomatous) proliferation often associated with Touton giant cells. The diagnosis is often challenging and not exclusively a histologic diagnosis, as it requires correlation with unique clinical, radiographic and recently described molecular findings. Activating mutations involving the MAPK pathway including BRAF, ARAF, N/KRAS and MEK are recurrent in the disease. However, it is increasingly being described that mutations associated with clonal hematopoiesis are also found in bone marrow specimens of patients with Erdheim-Chester disease (ECD), as well as higher frequency of overt concomitant myeloid malignancy including acute myeloid leukemia, myeloproliferative neoplasms, myelodysplastic syndromes, and mixed myeloproliferative neoplasms/myelodysplastic syndromes. Herein, we report a unique case of a patient presenting with BRAF-V600E-positive ECD with with peripheral blood findings consistent with a concurrent myeloid malignancy featuring co-occurrence of NRAS and IDH-2 mutations.

Mucosa-associated lymphoid tissue (MALT) lymphomas are often multifocal with patchy distribution that can be scattered throughout an involved organ. Previous studies have shown that each of these surrounding foci is often clonally related. Less is known about the clonal relationship of MALT lymphomas that involve multiple different organ systems. To investigate the clonal relationship of MALT lymphomas that involve multiple different organ systems, we retrospectively reviewed records of all marginal zone lymphoma from our database. Three cases were found to have multiple organ involvement and subjected to the analysis of the rearranged immunoglobulin variable regions using a polymerase chain reaction"“based assay. Three cases of MALT lymphomas arising from multiple sites include liver and lung, gastric and lung, nasopharynx, and parotid. Our results demonstrate that two of these cases show a clonal relationship; however, one case appears clonally distinct and appears unrelated. With reviewing the literature of MALT lymphomas that involve multiple different organ systems, it overall supports that clearly these have the potential to disseminate to other extranodal locations; however, involvement of multiple different organ systems should not necessarily be considered definitive evidence for disseminated or advanced disease.

Extranasal natural killer/T-cell lymphoma arising in the heart is rare and typically presents with non-specific clinical symptoms, necessitating a biopsy for a definitive diagnosis. We report an unusual case of a 48-year-old male who initially presented with chest pain and shortness of breath. Subsequent diagnosis via pericardial fluid analysis, including flow cytometry and immunohistochemical stains, revealed extranasal NK/T-cell lymphoma without sinonasal involvement. The analysis identified neoplastic lymphoid cells expressing CD2, cytoplasmic CD3, Epstein-Barr virus, and CD56 and exhibiting increased Ki-67 staining. Additionally, the patient developed hemophagocytosis lymphocytosis secondary to NK/T cell lymphoma. Treatment included an interleukin-1 receptor antagonist (anakinra), dexamethasone, rituximab, and etoposide. Unfortunately, the patient's condition rapidly deteriorated, leading to multiorgan failure and eventual demise. Given the rarity of this lymphoma, early diagnosis based on a high suspicion level provides the best chance for improved overall survival.

Pronator syndrome is a median nerve entrapment neuropathy that can be difficult to diagnose due to its variable presentation and objective findings. Neurolymphomatosis is an uncommon disease in which malignant lymphocytes infiltrate central or peripheral nerve endoneurium and is often missed for prolonged periods prior to diagnosis. We present a rare case of pronator syndrome and anterior interosseous nerve palsy due to neurolymphomatosis that was occult on initial MRI in spite of the presence of a median nerve mass discovered intra-operatively during neurolysis. This case demonstrates the value of ultrasound for the examination of peripheral nerve pathology and illustrates its utility as an adjunct to MRI, in part due to the ability to screen a large region.

Introduction: Pediatric-type follicular lymphoma (PTFL) is a rare B-cell lymphoma that primarily affects the head and neck, accounting for approximately 1.5"“2% of childhood lymphomas. Distinguishing between follicular lymphoma and PTFL is critical due to their distinct clinical characteristics, which influence prognosis and treatment. Case presentation: Two patients, a 14-year-old male (Case 1) and a 17-year-old male (Case 2), presented to the pediatric otolaryngology clinic with complaints of an isolated neck and parotid masses, respectively. In Case 1, physical examination revealed a 5 cm upward-growing neck mass without accompanying B symptoms or discomfort. CT scan, needle biopsy, and MRI with contrast confirmed the presence of the mass, which was subsequently surgically excised. In Case 2, the patient had an enlarging left-sided parotid mass, along with night sweats, fatigue, and arthralgias. Ultrasound and contrast-enhanced MRI confirmed a well-defined solid vascular mass within the left parotid gland, which was subsequently surgically excised. Pathological examination confirmed PTFL in both cases, leading to a positron emission tomography (PET)/CT scan for further evaluation and staging. Conclusion: This case series underscores the importance of pediatric surgeons to consider PTFL in the differential diagnosis of head and neck masses, as it can be effectively cured through surgical excision.

Extranasal natural killer/T-cell lymphoma arising in the heart is rare and typically presents with non-specific clinical symptoms, necessitating a biopsy for a definitive diagnosis. We report an unusual case of a 48-year-old male who initially presented with chest pain and shortness of breath. Subsequent diagnosis via pericardial fluid analysis, including flow cytometry and immunohistochemical stains, revealed extranasal NK/T-cell lymphoma without sinonasal involvement. The analysis identified neoplastic lymphoid cells expressing CD2, cytoplasmic CD3, Epstein-Barr virus, and CD56 and exhibiting increased Ki-67 staining. Additionally, the patient developed hemophagocytosis lymphocytosis secondary to NK/T cell lymphoma. Treatment included an interleukin-1 receptor antagonist (anakinra), dexamethasone, rituximab, and etoposide. Unfortunately, the patient’s condition rapidly deteriorated, leading to multiorgan failure and eventual demise. Given the rarity of this lymphoma, early diagnosis based on a high suspicion level provides the best chance for improved overall survival.

Extranasal natural killer/T-cell lymphoma arising in the heart is rare and typically presents with non-specific clinical symptoms, necessitating a biopsy for a definitive diagnosis. We report an unusual case of a 48-year-old male who initially presented with chest pain and shortness of breath. Subsequent diagnosis via pericardial fluid analysis, including flow cytometry and immunohistochemical stains, revealed extranasal NK/T-cell lymphoma without sinonasal involvement. The analysis identified neoplastic lymphoid cells expressing CD2, cytoplasmic CD3, Epstein-Barr virus, and CD56 and exhibiting increased Ki-67 staining. Additionally, the patient developed hemophagocytosis lymphocytosis secondary to NK/T cell lymphoma. Treatment included an interleukin-1 receptor antagonist (anakinra), dexamethasone, rituximab, and etoposide. Unfortunately, the patient"™s condition rapidly deteriorated, leading to multiorgan failure and eventual demise. Given the rarity of this lymphoma, early diagnosis based on a high suspicion level provides the best chance for improved overall survival.

BACKGROUND:Large granular lymphocytic leukemia is a rare lymphocytic neoplasm that can pose a treatment challenge in patients with severe neutropenia in whom conventional therapies fail. We report one of the first cases in which allogeneic stem cell therapy was used as treatment for large granular lymphocytic leukemia. We report and discuss the case of a 42-year-old white Caucasian female who, despite multiple therapies including methotrexate, cyclophosphamide, prednisone, cyclosporine, and pentostatin, continued to show severe neutropenia and recurrent infections. The patient was treated successfully and cured by allogeneic stem cell transplant without any major complications. CONCLUSIONS:The significant importance of this case report is the introduction of a new treatment algorithm for challenging cases of T-cell large granular lymphocytic leukemia in which standard care fails. We hope that this case report will raise awareness of the potential benefits of allogeneic stem cell transplant in the treatment of aggressive forms of T-cell large granular lymphocytic leukemia.

Anaplastic large cell lymphoma is a relatively rare type of T cell lymphoma characterized by strong and uniform CD30 expression with a typical cohesive growth pattern and hallmark cells. Most cases are single-positive for CD4 or less often CD8-positive, with only very rare descriptions of having double positivity for both antigens. Agent Orange is a herbicide which was used during the Vietnam War and has been associated with non-Hodgkin lymphoma (including chronic lymphocytic leukemia, hairy cell leukemia, and other chronic B cell leukemias), Hodgkin lymphoma and monoclonal gammopathy of undetermined significance. Herein, we describe a unique case of anaplastic large cell lymphoma ALK-negative arising in a military veteran with documented Agent Orange exposure featuring double positivity for both CD4 and CD8 with a brief literature review that highlights the uniqueness of this rare phenotype. Our patient underwent a left neck lymph node biopsy that was worked up for a lymphoproliferative process. Based on the diagnosis rendered, a T cell lymphoma fluorescence in situ hybridization [FISH] panel was done. T cell receptor gene rearrangement studies could not be performed due to consumption of the material. A core biopsy of the left neck lymph node showed an infiltrate of frankly malignant large lymphoid cells with many featuring eccentric horseshoe/kidney shaped nuclei with an eosinophilic region near the nucleus, consistent with hallmark cells with admixed small lymphocytes, plasma cells and few neutrophils and eosinophils. The neoplastic cells were positive for CD45, CD30, CD2 [subset +], CD5, and also showed double-positive [DP] CD4 + CD8 + and were negative for CD3. FISH studies for T cell lymphoma FISH panel that included rearrangements involving ALK, TP63 and DUPS22 [IRF4] gene regions were negative. Through this case, we demonstrate a unique case of anaplastic large cell lymphoma, ALK-negative in a patient with Agent Orange exposure and featuring double positivity for CD4 and CD8.