A Case of Persistent Lung Masses After Treatment of Hodgkin Lymphoma.

CASE PRESENTATION: The patient is a 49-year-old woman who had never used tobacco with a history of relapsing polychondritis and episcleritis. She sought treatment at our clinic for evaluation of multiple lung masses. She originally received a diagnosis by chest radiography performed to rule out sarcoidosis as the cause of episcleritis showing an abnormal findings. She had no contributory surgical, family, or social history. The autoimmune markers were notable for positive rheumatoid factor (153 IU/mL) and elevated erythrocyte sedimentation rate (97 mm/h) and C-reactive protein (65.5 mg/L). Pertinent studies with negative results included antineutrophilic cytoplasmic antibody, antinuclear antibody, cyclic citrullinated peptide antibody, Sjogren syndrome-related antigen A, and Sjogren syndrome-related antigen B tests.

A Rare Case of Non-IgM Lymphoplasmacytic Lymphoma with Unusual Lack of Immunoglobulin Light Chain Production.

BACKGROUND Non-IgM lymphoplasmacytic lymphoma (LPL) is a rare subtype of LPL, constituting less than 5% of the cases, and is often associated with IgG, IgA, or light chain paraproteins and is rarely a non-secretor. Non-IgM LPL remains poorly studied, and the differential diagnosis from other small B-cell lymphomas with plasmacytic differentiation and plasma cell neoplasm is challenging. CASE REPORT A 67-year-old woman presented with weight loss, persistent anemia, and borderline leukopenia. Serum protein electrophoresis and immunofixation demonstrated a faint IgG and kappa band against a dense polyclonal background. Bone marrow biopsy revealed hypercellular marrow with involvement by abnormal B cells with undetectable surface and cytoplasmic immunoglobulin light chains. Interestingly, these B cells showed no expression of light chains or production of IgG and IgM; however, they showed production of intracytoplasmic IgA. The concomitant neoplastic plasma cells also displayed no definitive light chain expression. Both IgH and IgK gene rearrangements were positive for clonal process. Molecular studies showed positive MYD88 L265P mutation and CXCR4 mutation (c.1013C>G). The overall findings confirmed marrow involvement by non-IgM LPL. The patient received 6 cycles of rituximab and bendamustine treatment, and no residual marrow involvement was found on the follow-up bone marrow biopsy. CONCLUSIONS We report a non-IgM LPL case featuring no light chain production and no heavy chain secretion, which we believe is the first reported case of this kind in the literature.

ALK-positive Large B-Cell Lymphoma With Multiple Epithelial Antigen Expression and PABPC1::ALK Fusion : A Novel Molecular Alteration.

Anaplastic lymphoma kinase (ALK)-positive large B-cell lymphoma (LBCL) is a very rare type of LBCL with an aggressive clinical course and poor prognosis. This diagnosis can be challenging given the varied morphology (immunoblastic, plasmablastic, or anaplastic), frequent lack of B-cell antigens, and especially in cases with expression of epithelial antigens. Here, we report a case of ALK-positive LBCL with unusual expression of 4 epithelial-associated markers (AE1/AE3, CK8/18, EMA, and GATA3) and novel poly(A) binding protein cytoplasmic 1 (PABPC1) :: ALK fusion which has not been previously reported in this entity. This case also emphasizes the use of comprehensive immunophenotyping that includes multiple lineage-specific antibodies when faced with a malignancy without a clear differentiation to avoid misdiagnosis. This case only achieved partial response to combination chemotherapy, radiation, and ALK inhibitor regimens, and furthers our understanding of this uncommon lymphoma.

Exploring the Rare Etiology of Severe Anemia in an Immunocompromised Patient.

Pure red cell aplasia (PRCA) is a rare cause of profound anemia, marked by very low reticulocyte count and near to complete absence of erythroid precursor cells in the bone marrow. PRCA can be congenital such as in the case of children with Diamond- Blackfan anemia or acquired, which is often triggered by exposure to certain viruses or drugs. Management depends on the underlying etiology of PRCA. Here, we present the case of a young male with underlying acquired immunodeficiency syndrome, who presented with a hemoglobin of 2.6 g/dL, initially thought to be secondary to gastrointestinal blood loss, but was later discovered to have parvovirus-induced PRCA.

Primary Dural Lymphoma Mimicking En Plaque Cerebellopontine Angle Meningioma.

Primary dural lymphoma (PDL) usually arises from the calvarial dura without the brain parenchyma or systemic involvement and thus may not be considered as a typical form of primary CNS lymphoma (PCNSL). It is exceedingly rare. When it occurs, it might not be suspected as a primary diagnosis on clinical and radiologic findings. We present a PDL case that occurs at the cerebellopontine (CP) angle mimicking en plaque meningioma. The tumor histopathology showed a lymphoproliferative disorder immunophenotypically consistent with a low-grade marginal zone lymphoma. Bone marrow and systemic involvements were not identified, and a diagnosis of PDL was established. As a residual tumor at the CP angle was inaccessible to surgery, postoperative radiation therapy was performed. No recurrence was found at 15-month follow-up. PDLs are mostly indolent and have a good prognosis. There is no doubt that the most important differential diagnosis is meningioma. Furthermore, the present case emphasizes the necessity of an intraoperative consultation and knowledge of this rare yet essential form of PCNSL so that appropriate studies can be ordered.

Hypercalcemia in Small Lymphocytic Lymphoma with an Elevated Parathyroid Hormone-Related Peptide Associated with Early Richter Transformation.

Hypercalcemia in malignancy is associated with multiple mechanisms and occurs in up to 20-30% of cancer patients. We report a case of small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) associated with hypercalcemia and an elevation in parathyroid hormone-related peptide (PTHrP) in the setting of a Richter transformation. Real-time reverse transcriptase PCR on lymph node biopsy specimens obtained before and after transformation showed an 8-fold increase in PTHrP mRNA levels and about 2-fold decrease in the levels of its cognate receptor PTHR1. The findings of this case suggest that parathyroid hormone-related peptide might be useful in monitoring a specific group of patients with SLL/CLL who develop hypercalcemia during the course of their disease and could suggest an autocrine-like mechanism involving PTHrP in Richter transformation.

Lymphoid neoplasms of the oral cavity with plasmablastic morphology-a case series and review of the literature.

Plasmablastic lymphoma (PBL) is a rare aggressive variant of large B-cell lymphoma defined as a proliferation of large neoplastic plasmablasts/immunoblasts. PBL was first described as a distinct entity in a group of 16 patients with lymphoma of the oral cavity. Most patients are HIV-positive men. The disease has also been reported in other patient groups, often in association with primary or other acquired immunodeficiency. PBL shows a predilection for the oral cavity, although extraoral involvement also occurs. Because of its rarity, unique clinical features, and overlapping morphologic/immunophenotypic features, care must be taken to distinguish PBL from diffuse large B-cell lymphoma and plasma cell neoplasms with plasmablastic features. We report 3 cases of neoplasms with plasmablastic histomorphology involving the oral cavity. The relevant clinical, morphologic, and immunophenotypic features and treatment are presented, along with a review of the literature.

Severe Type B Lactic Acidosis in a Rare and Aggressive HIV-Related Lymphoma.

We describe the prognostic implication and aggressive clinical course of lymphoma-related lactic acidosis in a rare HIV-related lymphoma. Patient was diagnosed with plasmablastic lymphoma and developed severe lactic acidosis, and was treated on the medical floor and in the medical intensive care unit. Her lactic acidosis was considered to be type B, secondary to her underlying lymphoma since she never had an infectious source, hypovolemic state, or low/high cardiac-output state. The mechanism of the lymphoma-related lactic acidosis is from altered cellular metabolism, thought to aid in lymphoma proliferation, rather than tissue hypoperfusion. It is a rare complication of aggressive lymphomas and signifies a poor prognosis. Patients having this complication should be considered for close monitoring and management in an intensive care unit until definitive treatment (i.e., chemotherapy) can be implemented.

Analysis of TET2 mutations in paroxysmal nocturnal hemoglobinuria (PNH).

BACKGROUND: Large clonal populations of cells bearing PIG-A mutations are the sine qua non of PNH, but the PIG-A mutation itself is insufficient for clonal expansion. The association between PNH and aplastic anemia supports the immune escape model, but not all PNH patients demonstrate a history of aplasia; therefore, second genetic hits driving clonal expansion have been postulated. Based on the previous identification of JAK2 mutations in patients with a myeloproliferative/PNH overlap syndrome, we considered TET2 as a candidate gene in which mutations might be contributing to clonal expansion. METHODS: Here we sequenced the TET2 and JAK2 genes in 19 patients with large PNH clones. RESULTS: We found one patient with a novel somatic nonsense mutation in TET2 in multiple hematopoietic lineages, which was detectable upon repeat testing. This patient has had severe thromboses and has relatively higher peripheral blood counts compared with the other patients-but does not have other features of a myeloproliferative neoplasm. CONCLUSIONS: We conclude that mutations in TET2 may contribute to clonal expansion in exceptional cases of PNH.

Mediastinal Lymphoma Presenting in Cardiogenic Shock with Superior Vena Cava Syndrome in a Primigravida at Full Term: Salvage Resection after Prolonged Extracorporeal Life Support.

Primary mediastinal large B-cell lymphoma (PMBCL) is a rare type of non-Hodgkin lymphoma that typically has a good response rate to first line chemotherapy regimens. There have been reports of successful chemotherapy, but with a residual mass from fibrosis. Here, we report the case of a 19-year-old primigravida presenting with cardiogenic shock and superior vena cava (SVC) syndrome at full term who was found to have a PMBCL. Following delivery via urgent cesarean section, she was put on veno-arterial extra corporeal membrane oxygenation (VA-ECMO) and once hemodynamically stable was started on chemotherapy. In view of limited change in tumor size on consecutive CT scans and questionable response to chemotherapy, there were multidisciplinary meetings wherein withdrawing support was discussed and put forward to the family. At that point, surgical debulking was offered on compassionate grounds to be able to wean her off the VA-ECMO. This case report highlights the role of salvage resection when there are no other options.

Primary extranodal jejunal diffuse large B cell lymphoma as a diagnostic challenge for intractable emesis: a case report and review of literature.

Introduction: The gastrointestinal tract is the most common extranodal site for non-Hodgkin's lymphoma, with the most common being diffuse large B cell lymphoma. Unlike the stomach or the ileum, the jejunum is a rare site for primary extranodal lymphomas, given the scarcity of lymphoid tissue. Due to its location, inflammation in the jejunum may not be visualized on routine imaging or endoscopy, making jejunal lymphoma difficult to diagnose. Case Description: We present a case of a 90-year-old male with 1 week of intractable emesis, initially thought to be due to viral gastroenteritis. His symptoms never improved and he underwent serial CT imagings in addition to esophagogastroduodenoscopy. A stomach biopsy and a diagnostic paracentesis did not reveal any malignant cells, but a CT enterography revealed significant jejunal inflammation with obstruction. After a month of hospitalization, a jejunal biopsy was obtained, which showed proliferation of neoplastic B cells. He was ultimately diagnosed with primary jejunal diffuse large B cell lymphoma. Discussion: Chemotherapy and surgical resection are typically the definitive treatment for extranodal lymphoma. Clinicians, however, must carefully consider the patient's functional and nutritional statuses before offering such interventions. This case was a diagnostic challenge and demonstrated a rare GI malignancy's convoluted mimicking nature.

Rosai-Dorfman disease of the breast: A potential marker of systemic disease.

Rosai-Dorfman disease (RDD) is a rare idiopathic benign proliferative disorder of histiocytes. RDD typically presents with cervical lymph node involvement; however, extranodal sites such as the breast can also be involved and should prompt evaluation for additional sites of disease.

Lymphoid malignancy-associated hemophagocytic lymphohistiocytosis: Search for the hidden source.

Secondary hemophagocytic lymphohistiocytosis (HLH) is an uncommon, but life-threatening syndrome of highly stimulated and ineffective immune dysregulation. It is not a disease entity by itself and the current diagnosis of secondary (acquired) HLH is based on constellation of nonspecific clinical and laboratory parameters indicative of overactive immune response. The presenting symptoms are often nonspecific and could potentially be missed, leading to a fatal outcome. Patients with malignancy-associated HLH have a relatively unfavorable overall survival compared with non-malignancy-associated HLH. In this retrospective study, nine adult patients with secondary HLH were identified. Of these four cases were associated with a malignancy and despite a high degree of suspicion, the underlying lymphoid malignancy was not initially evident. Three out of four patients with lymphoid malignancy-associated HLH died over a very short course of time following the diagnosis. The outcome was significantly different for the control group of patients with other underlying cause(s) for HLH. These cases emphasize the importance of a thorough search for a hidden malignant source in patients with secondary HLH for prompt diagnosis and institution of malignancy specific treatment.

Mucosa-Associated Lymphoid Tissue Lymphoma of the Sigmoid Colon Discovered on Routine Screening Colonoscopy in Patient with Hepatitis C and Helicobacter pylori Infection.

Mucosa-associated lymphoid tissue (MALT) lymphoma is predominantly found in the stomach. Rarely, it is found in the proximal colon and even less so in the sigmoid colon. We present a rare case of primary sigmoid colon MALT lymphoma in a patient with concomitant Helicobacter pylori and hepatitis C infection. We also review current imaging, staging, and therapeutic modalities. To our knowledge, this is the first sigmoid colon MALT lymphoma reported in the United States.