David D. Grier

Eosinophilic Gastroenteritis: Review of a Rare and Treatable Disease of the Gastrointestinal Tract

Eosinophilic gastroenteritis is a rare disease of the gastrointestinal tract characterized by crampy abdominal pain, nausea, vomiting, diarrhea, gastrointestinal bleeding, and weight loss associated with peripheral eosinophilia leading to eosinophilic infiltrates in stomach and intestine, usually in a patient with a prior history of atopy. In this article, we describe our encounter with a 59-year-old female presenting with severe abdominal pain, nausea, vomiting, and weight loss with an extensive evaluation including an upper endoscopy with biopsies resulting in a diagnosis of eosinophilic gastroenteritis. The patient was eventually treated with oral prednisone for three weeks with complete resolution of her symptoms.

Concomitant Occurrence of Sinus Histiocytosis With Massive Lymphadenopathy and Nodal Marginal Zone Lymphoma

Sinus histiocytosis with massive lymphadenopathy (SHML), also known as Rosai-Dorfman disease, is a rare self-limiting disorder of histiocytes with unknown etiology. Sinus histiocytosis with massive lymphadenopathy is most common in children and young adults and is characterized by painless lymphadenopathy. Histologically there is a proliferation of sinus histiocytes with lymphophagocytosis or emperipolesis. On rare occasions, SHML has been associated with lymphoma, usually involving different anatomic sites and developing at different times. We report a case of concomitant SHML and nodal marginal zone lymphoma involving the same lymph node without involvement of other nodal or extranodal sites. The presence of concomitant SHML within the lymph node involved by nodal marginal zone lymphoma may represent the responsiveness of SHML histiocytes to B-cell-derived cytokines in lymphoproliferative disorders. To our knowledge, this is the first description of concomitant occurrence of SHML and nodal marginal zone lymphoma.

Ferritin H is a novel marker of early erythroid precursors and macrophages

Macrophages play a critical role in iron homeostasis by recycling iron from red cells and storing it in ferritin, an iron storage protein. The recycled iron is delivered to erythroid precursors for erythropoiesis. In this study, we aimed to determine whether ferritin is highly expressed in macrophages and erythroid precursors, and whether it can be used as a marker for these two cell types.

Intracranial myeloid sarcoma

A 41-year-old female presented with a 2 d history of ‘refusing to talk’ and a 1 d history of ‘decreased movement’. She had a recent history of being treated for otitis media, but no history of malignancy. On admission, a full blood count and differential white cell count were normal. Magnetic resonance imaging revealed a 6 cm contrast-enhancing left-sided middle cranial fossa mass with extension inferiorly into the subtemporal fossa and parapharyngeal space (top left). The radiologist’s differential diagnosis included meningeal sarcoma, atypical meningioma, undifferentiated sinonasal cancer and lymphoma. A needle core biopsy was performed, but was nondiagnostic. Due to concerns about herniation and the lack of diagnostic tissue, the patient underwent a craniotomy. The cytospin and touch preparations from the tissue biopsy demonstrated a monomorphic population of atypical mononuclear cells with high nuclear:cytoplasmic ratios, vacuolated cytoplasm and prominent nucleoli (top right). Histological sections showed a diffuse infiltrate of large cells with large nuclei, irregular nuclear contours, prominent nucleoli and open chromatin (bottom left). The cells were positive for myeloperoxidase by immunohistochemistry. Flow cytometry detected myeloid blasts, which were CD34, CD13, CD33, CD117, CD20 and CD10. There was aberrant expression of CD19 and partial expression of CD56 (bottom right). Cytogenetic analysis demonstrated 45,X,-X, t(8;21;12)(q22;q22;q21). There was no evidence of bone marrow involvement by morphology or flow cytometry. The patient’s mental status improved dramatically after four cycles of cytarabine. She was lost to follow-up after 7 months. Myeloid sarcoma is an uncommon neoplasm and intracranial involvement comprises approximately 3% of all cases. Most are manifestations of previous or concurrent acute myeloid leukaemia although some may precede it. Intracranial myeloid sarcomas present as extra-axial masses and are believed to arise from the bone marrow of the skull. Histological differentiation between myeloid sarcoma and a large cell lymphoma can be difficult, if not impossible, without immunohistochemistry or flow cytometric analysis. Diagnosis can be especially problematic because these tumours can express B-cell antigens (e.g. CD19, CD79a), thus leading to the misdiagnosis of B-cell lymphoma.

Donor-Derived Myeloid Sarcoma in Two Kidney Transplant Recipients from a Single Donor

We report the rare occurrence of donor-derived myeloid sarcoma in two kidney transplant patients who received organs from a single deceased donor. There was no evidence of preexisting hematologic malignancy in the donor at the time of organ recovery. Both recipients developed leukemic involvement that appeared to be limited to the transplanted organ. Fluorescence in situ hybridization (FISH) and molecular genotyping analyses confirmed that the malignant cells were of donor origin in each patient. Allograft nephrectomy and immediate withdrawal of immunosuppression were performed in both cases; systemic chemotherapy was subsequently administered to one patient. Both recipients were in remission at least one year following the diagnosis of donor-derived myeloid sarcoma. These cases suggest that restoration of the immune system after withdrawal of immunosuppressive therapy and allograft nephrectomy may be sufficient to control HLA-mismatched donor-derived myeloid sarcoma without systemic involvement.

Burkitt’s Lymphoma Presenting as Late-Onset Posttransplant Lymphoproliferative Disorder following Kidney and Pancreas Transplantation: Case Report and Review of the Literature

Posttransplant lymphoproliferative disorders (PTLD) are a rare, but serious complication following transplantation. Late-onset PTLD are often associated with more monoclonal lesions and consequently have a worse prognosis. There are only isolated case reports of Burkitt’s lymphoma presenting as PTLD. We present an extremely rare, aggressive Burkitt’s lymphoma years after kidney and pancreas transplantation which was successfully treated with combination chemotherapy along with withdrawal of immunosuppression. The patient remains in complete remission more than 2 years after his diagnosis. We also provide a succinct review of treatment of various PTLD and discuss the role of Epstein-Barr virus infection in the pathogenesis of PTLD.

Signet-ring plasma cell myeloma.

A 26-year-old man presented with right upper hip pain. A CT scan showed a 6.0 3 6.0 3 7.0 cm lytic lesion in the right iliac wing with significant soft tissue involvement. A fine-needle aspiration of the lesion revealed numerous atypical plasma cells consistent with a plasmacytoma. Flow cytometry confirmed the diagnosis. A radiological bone survey revealed a single 7-mm well-defined lucent focus at the front aspect of the lateral skull. By serum protein electrophoresis and immunofixation, the patient had an IgG kappa M-spike estimated at 2.76 g/dl. A bone marrow biopsy demonstrated an increased number of plasma cells by CD138 immunohistochemistry (approximately 10–15% of the total marrow space). On the aspirate smears and touch preparations, the plasma cells were remarkable for large basophilic globules that markedly compressed the nuclei (Image 1). Bone marrow core biopsy sections revealed numerous refractile globular structures (Image 2). The patient’s bone marrow findings, imaging, and laboratory findings are consistent with the diagnosis of a plasma cell myeloma. The morphologic presentation of plasma cell myeloma varies from benign appearing mature plasma cells to anaplastic variants. The unusual plasma cell morphology seen in this biopsy, with large immunoglobulin inclusions, has been referred to in the literature as ‘‘signet-ring’’ or ‘‘clear cell’’ plasma cell myeloma. Signet-ring myeloma is exceptionally rare with only a handful of reported cases in the literature [1–6]. The accumulation of intracellular immunoglobulin is most likely from defective immunoglobulin assemblage. In one case of plasmacytoma with signet ring features, the inclusions were amyloid [1]. Awareness of this morphologic variant is crucial to avoid the misdiagnosis of other neoplasms with signet ring features, such as metastatic adenocarcinoma, liposarcoma [3], or B-cell non-Hodgkin lymphoma [7]. It should be noted that adenocarcinomas can express CD138, therefore this immunohistochemical stain cannot be used solely to rule out metastatic carcinomas [8].

An unusual case of acute myeloid leukemia: Late isolated testicular relapse followed by isolated central nervous system relapse†

Testicular relapse of acute myeloid leukemia without bone marrow involvement is a rare event. We describe a case of an 18‐year‐old male who had an isolated testicular relapse 86 months (7.2 years) from original diagnosis. He was treated with surgery only, without adjuvant therapy. The patient then developed central nervous system involvement 9 months later. Fluorescence in situ hybridization and immunohistochemistry were used to establish the diagnosis of a relapse rather than a new leukemic process. He was treated with intrathecal chemotherapy and systemic reinduction, followed by a stem cell transplant. This patient had a 7.2‐year period between original diagnosis and the testicular relapse of acute myeloid leukemia. Pediatr Blood Cancer. 2010;55:1231–1233.

Case study interpretation—Portland: Case 3

CASE HISTORY A 66-year-old female with a past medical history significant for diabetes mellitus presented to an outside emergency department after a 5-month history of fatigue, night sweats, and a 24 lb (11.3 kg) weight loss. Labs performed at the outside institution revealed circulating cells suspicious for blasts, white blood cell count (WBC) of 11.3 10/L, hemoglobin (Hb) of 7.6 g/dL, and a platelet count of 8 10/L. She was transferred to our institution for evaluation and treatment for acute leukemia. Laboratory findings revealed a WBC of 10.4 10/L, Hb 5.4 g/dL, platelets of 11 10/L, 44% ‘‘blasts’’ on the peripheral blood smear, and a lactate dehydrogenase of 12,242 U/L (normal 105–333 U/L). A bone marrow biopsy was performed as well as a thoracentesis to alleviate a pleural fusion. Intermediate-sized lymphoid cells with scant dark blue cytoplasm and cytoplasmic vacuoles were seen in the bone marrow, peripheral blood, and pleural fluid. Flow cytometry was performed on the bone marrow and pleural fluid samples. The patient’s condition deteriorated despite aggressive chemotherapy and the patient died four days after admission.

Bone marrow involvement by Pneumocystis jiroveci

A 34-year-old female with a 5-year history of cutaneous T-cell lymphoma presented to the emergency department with shortness of breath, abdominal distention and lower extremity oedema. The peritoneal fluid revealed organisms consistent with pneumocystis, which was confirmed by immunofluorescent antibody assay. A full blood count showed pancytopenia and a bone marrow biopsy was performed. The bone marrow aspirate smears showed normal multilineage haematopoiesis with focal aggregates of foamy eosinophilic material similar in appearance to megakaryocyte cytoplasm or fibrin (top left). Similar aggregates were seen in the bone marrow core biopsy (top right and bottom left). Gomori’s methenamine silver (GMS) stain demonstrated numerous cup-shaped organisms consistent with pneumocystis species (bottom right). The patient’s hospital stay was complicated by coagulopathy and a large retroperitoneal haemorrhage. Her spleen was removed during a laparotomy and pathological examination revealed extensive involvement by pneumocystis. She eventually died from multisystem organ failure exacerbated by disseminated pneumocystis, candida and cytomegalovirus infections. Pulmonary Pneumocystis jiroveci infection is common in immunodeficient patients. Prior to the acquired immunodeficiency syndrome epidemic, extrapulmonary pneumocystosis was a rare event, with 16 reported cases. Since the early 1980s there have been numerous case reports of extrapulmonary pneumocystosis involving the lymph nodes, spleen, liver, thyroid, eye, skin, bone marrow, pituitary gland, kidney and adrenal glands. Extrapulmonary pneumocystosis typically occurs in patients with advanced human immunodeficiency virus infection who are not receiving pneumocystosis prophylaxis. The foamy eosinophilic material, most commonly seen in bronchoalveolar lavage specimens, is believed to be composed of membrotubular extensions between cysts and trophozoites, cell debris and fibrin. In bone marrow aspirate smears this material has a very similar appearance to megakaryocyte cytoplasm or fibrin, and could easily be overlooked. These deposits are much more recognisable on a bone marrow core biopsy or clot section with a GMS stain confirming the diagnosis.