Large Lymphoid Cells Research Articles

Hemophagocytosis as the initial presentation in a patient with myelodysplastic syndrome and coexisting NK/T cell lymphoma involving bone marrow

A 60-year-old man with uremia undergoing regular hemodialysis was admitted due to general weakness and dizziness persisting for 1 month. He denied any history of smoking, alcoholism and exposure to chemical or radiation. Initial physical examination noted marked pallor of the conjunctiva and skin, distended but nontender abdomen with splenomegaly (10 cm below the left costal margin) and grade 2 pitting edema in lower extremities. No peripheral lymphadenopathy was found. He presented with the following on workup: complete blood count (CBC) including hemoglobin, 6.3 g/dL; white blood cell count (WBC), 21.77 9 10/L (1 % blast, 4 % band form, 38 % segmented neutrophils, 19 % lymphocytes, 32 % monocytes) and platelets, 29 9 10/L. Biochemical data were all within normal limits, apart from ferritin, 865 ng/mL (normal range 38–280 ng/mL); sodium, 128 mEq/L; blood urea nitrogen, 148 mg/dL; creatinine, 11.26 mg/dL; albumin, 3.3 g/dL; prothrombin time, 12.3 s; activated partial thromboplastin time, 38.4 s, and prothrombin time of international normalized ratio (INR) 1.19. Lactate dehydrogenase level was 176 U/L (normal range 131–250 U/L). Computed tomography detected multiple enlarged lymph nodes in gastrohepatic ligament, celiac trunk root, mesenteric root, aortocaval and left para-aortic retroperitoneal regions, as well as splenomegaly. Bone marrow (BM) aspirate showed a hypercellular marrow with increased tissue histiocytes and evident hemophagocytic activity (Fig. 1). Hematological malignancy such as leukemia or lymphoma was first considered. Marked dysplastic features involving megakaryocytes, myeloid (Fig. 2, arrow) and erythroid (Fig. 3, arrow) series and left shift maturation with 11 % myeloblast, 9 % promyelocytes were noted in BM aspirate. Excess blasts in BM aspirate were also noted (Figs. 2, 3, arrowhead). In addition, aggregates of immature lymphoid cells, about 19 %, coexisted with the dysplastic marrow. Immunocytochemical stain confirmed concomitant presence of myeloperoxidase-positive myeloblasts and acid-phosphatase-positive T-lymphoblasts. Iron staining showed no increased iron storage or ringed sideroblasts. Cytogenetic analysis of the bone marrow revealed monosomy 7, a common myelodysplastic syndrome (MDS)-associated cytogenetic abnormally indicating poor prognosis. Flow cytometry immunophenotype analysis of BM revealed two abnormal clones of cells: myeloid precursor cells resembling myeloblasts were positive staining for human leukocyte antigen (HLA)-DR (97 %), CD34 (35 %), CD13 (94 %) and CD33 (96 %); abnormal lymphoid populations showed positive for CD2 (80 %) and CD7(83 %). BM biopsy showed vaguely nodular infiltration of atypical medium to large lymphoid cells in the marrow by hematoxylin and eosin (HE) stain (Fig. 4), excess of myeloblasts (10 %) with positive staining in CD34 (Fig. 5) and myeloperoxidase. In addition, BM biopsy revealed focally nodular infiltration of atypical medium to large lymphoid cells with Y.-C. Liu J.-P. Gau C.-Y. Liu (&) Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sec 2, Shi-Pai Road 112, Taipei, Taiwan e-mail: cyliu3@vghtpe.gov.tw

Unremitting pyrexia, pancytopenia, hepatosplenomegaly, and extreme hyperferritinemia

Unremitting pyrexia, pancytopenia, hepatosplenomegaly, and extreme hyperferritinemia

Transformed lymphoplasmacytic lymphoma involving the main carina: A case report

A 41-year-old male was admitted to Nagoya City University Hospital subsequent to experiencing a cough with bloody sputum for a few days. The patient had a 4-year history of lymphoplasmacytic lymphoma (LPL) and had achieved a good partial response to anticancer chemotherapy. Chest computed tomography (CT) showed an endobronchial tumor of the main carina. A bronchoscopy revealed an exophytic tumor at the main carina, and autofluorescence imaging bronchovideoscopy showed that the tumor and surrounding area were magenta in color. The biopsy specimens demonstrated that the endobronchial tumor was composed of large atypical lymphoid cells. The patient was diagnosed with a high-grade transformation of LPL. In addition to describing a rare case of transformed LPL involving the main carina, the present study also summarizes and discusses endobronchial lymphomas, with a brief review of a number of published studies.

Primary cutaneous CD4 positive small/medium T-cell lymphoma with high proliferation index and CD30-positive large lymphoid cells

Primary cutaneous CD4 positive small/medium pleomorphic T-cell lymphoma (SMPTCL) represents a provisional subtype of primary cutaneous T-cell lymphoma with indolent clinical course. A few aggressive fatal cases with increased proliferation rate and few infiltrating CD8 positive T-cells have been reported. We describe a case of SMPTCL with an increased proliferation rate, admixed CD30-positive large lymphoid cells, and few infiltrating CD8 positive T-cells. The lymphoma cells were positive for CD3, CD4, CD2 and CD5, and negative for CD8. A subset of the lymphoma cells was positive for follicular helper T-cell markers bcl-6 and PD-1. There were approximately 20% CD30-positive large lymphoid cells, and Ki-67 showed a moderately high proliferation rate (~40%), mostly in the large lymphoid cells. CD8 infiltrating T-cells were few (<5%). The patient had an indolent disease with complete response to radiation therapy. To the best of our knowledge, this is the first reported case of SMPTCL with an increased proliferation rate and large CD30+ cells that followed an indolent clinical course.

English

AIMS: To determine the cause for massive splenomegaly. MATERIALS AND METHODS: Splenectomy was done and sections given from cut surface. They were stained with haemotoxylin & eosin and microscopically analysed. Immunohistochemical study was done for a panel of antibodies including CD5, CD10, CD20, bcl-2 & cyclin D1. RESULTS: Microscopy showed effacement of the normal architecture along with a nodular architecture in the white pulp with small lymphocytes surrounded by medium to large lymphoid cells with dispersed chromatin and abundant pale cytoplasm which resembled the marginal zone cells. Immunohistochemical study showed positivity for CD20 and bcl -2. It was negative for CD5, CD10 and Cyclin D1. Considering all the findings a diagnosis of Splenic Marginal Zone Lymphoma (SMZL) was made. CONCLUSION: In this case, clinically lymphoma was not suspected, as splenomegaly was the only finding. Patient was thoroughly investigated for various causes of splenomegaly but only histopathological evaluation of spleen along with IHC study was diagnostic.

Paediatric T-cell lymphoma of the appendix: a case report

A 7-year-old boy with no history of malnutrition or diarrhoea complained of acute abdominal pain, was diagnosed with acute appendicitis, and underwent appendectomy. Histologically, a diffuse infiltrate of large atypical lymphoid cells was found in the entire appendiceal wall. Immunohistochemical examination revealed that the tumour cells expressed T-cell receptor (TCR)-βF1, CD3, CD4, CD25, cytotoxic-related protein TIA1 and granzyme-B, but were negative for CD8, Foxp3, CD20, CD30 and CD56. Polymerase chain reaction (PCR) revealed clonal bands of TCR-γ gene products in the tumour tissue. No anti-cytomegalovirus antibody-positive cells were detected. In situ hybridization revealed no nuclear signals of Epstein-Barr virus (EBV)-encoded RNA. Helicobacter pylori infection was detected in tumour tissue by anti-East Asian cytotoxin-associated gene (Cag) A antibody and PCR using its specific primers. The patient received chemotherapy and has remained in remission for 2 years. To the best of our knowledge, only two cases of appendiceal T-cell non-Hodgkin lymphoma (NHL) have been reported, both in elderly patients. We believe that this is the first reported case of childhood CD4- and TIA1-positive cytotoxic T (Th1)-cell NHL in the appendix or gastrointestinal tract. Helicobacter pylori infection might be an initiator of atypical cytotoxic T-cell proliferation.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1302380563830412.

Diffuse large B cell lymphoma (DLBCL) presenting as a spindle cell tumor of the liver: a case report

Diffuse large B cell lymphoma (DLBCL) may present rarely as a spindle cell tumor. Only one previous case of spindle cell DLBCL involving the liver has been reported. We present a case of primary hepatic DLBCL with spindle cell features in a 67-year-old man who initially presented with elevated liver enzymes and an indistinct liver mass identified by computed tomography. The lesion was diagnosed by needle biopsy as an inflammatory pseudotumor at an outside hospital and repeat imaging suggested that the lesion had decreased in size. Thus, no treatment was given. Seven months later, he presented with jaundice and additional porta hepatic mass and lymphadenopathy. A surgical resection was performed. Microscopically, the liver mass, bile duct mass, and lymph nodes demonstrated a spindle cell infiltration interspersed with small and large lymphocytes, and eosinophils in a fibrotic background. One lymph node showed focal architectural effacement by large atypical lymphoid cells. Immunohistochemical staining of the lymph node and liver mass revealed that the tumor cells were positive for CD20, BCL-6, CD79a, and PAX-5. Proliferation index (Ki-67) ranged from 70 to 90 %. We concluded that both the liver and lymph nodes were involved by spindle cell DLBCL. This case is presented to underscore the importance of including DLBCL in the differential diagnosis of spindle cell lesions, especially those found in unusual locations such as the liver.

Gain of 11q by an Additional Ring Chromosome 11 and Trisomy 18 in CD5-Positive Intravascular Large B-Cell Lymphoma

Chromosomal abnormalities of intravascular large B-cell lymphoma (IVLBCL), a rare form of extranodal diffuse large B-cell lymphoma, have been described in only a small number of cases. A 59-year-old female presented with pancytopenia and splenomegaly. Bone marrow was normocellular with 30.4% abnormal large lymphoid cells that were positive for CD5, CD19, CD20, HLA-DR and λ chain. Bone marrow biopsy showed intrasinusoidal infiltration of large lymphoid cells. G-banding and spectral karyotyping of the bone marrow cells demonstrated a complex karyotype as follows : 48,XX,-8,+r(11),+12,del(12)(p?) ×2,+18,der(19)(19?::p13 → qter),der(21)t(8;21)(q11.2;p11.2). Fluorescence in situ hybridization on interphase nuclei revealed three signals of CCND1 at 11q13, but two signals of BIRC3 at 11q22 and MLL at 11q23, indicating that r(11) contained CCND1. Together with other reported cases, our results indicate that the gain of 11q as well as trisomy 18 may be among the recurrent chromosomal aberrations in IVLBCL. Furthermore, an additional ring chromosome 11 could be a novel mechanism leading to the gain of 11q.

Plasmablastic lymphoma of the colon in HIV-positive patient

Plasmablastic lymphoma (PBL) is a distinctive B-cell neoplasm which shows diffuse proliferation of large neoplastic cells, most of which resemble B-immunoblasts and have immunophenotype of plasma cells. PBL was originally described as a rare variant of diffuse large B-cell lymphoma (DLBCL) involving the oral cavity and occurring in the clinical setting of HIV [1] and latent Epstein-Barr virus (EBV) infection. We report a case of 49 year old HIV positive male with PBL involving the colon and rectum, who initially presented with constipation and rectal bleeding. A CT scan was performed which showed peri-colonic infiltration, rectal wall thickening and involvement of iliac, inguinal and mesenteric lymph nodes. A subsequent colonoscopy showed multiple lesions in the colon and rectum. Biopsy of these lesions showed monotonous proliferation of large lymphoid cells with immunoblastic features and immunohistolochemical report was consistent with the PBL.

Diffuse large B-cell lymphoma, not otherwise specified of the palate: a case report

Diffuse large B-cell lymphoma (DLBCL) is the most frequent type of non-Hodgkin´s lymphoma found in oral and maxillofacial regions. A large number of cases may be biologically heterogeneous, which are commonly defined as DLBCL, not otherwise specified (NOS) by the World Health Organization (WHO-2008). The present case reports on an ulcer of raised and irregular edges, found on the border between the hard and soft palate, as the first and only manifestation of an extranodal non-Hodgkin lymphoma in an 85-year-old patient. Incisional biopsy was carried out, and the specimen revealed a proliferation of large lymphoid cells suggestive of diffuse large cell lymphoma. An immunohistochemical analysis was performed. EBV-RNA was assessed by in situ hybridization that also proved to be negative. Immunohistochemical and EBV analyses are important to avoid delays and inappropriate treatment strategies. Although advanced age is considered an adverse prognostic factor, early diagnosis did prove to be a key contributory factor in the cure of non-Hodgkin lymphoma. Key words:Diffuse large B-cell lymphoma, elderly, EBV.

Anaplastic Large Cell Lymphoma, ALK-Negative Presenting in the Rectum: A Case Report and Review of the Literature

ALK-negative anaplastic large cell lymphoma (ALCL, ALK－) is a CD30+ T-cell neoplasm composed of large lymphoid cells with abundant cytoplasm and pleomorphic nuclei that lacks expression of ALK protein. We describe a case of ALCL, ALK－with primary involvement of the rectum in a 37 year old man, where the original diagnosis was established based on a colonoscopic biopsy. T-cell lymphomas are rare in the colorectal area and besides ALCL, their differential diagnosis includes enteropathic T-cell lymphoma, peripheral T-cell lymphoma, not otherwise specified, NK/T cell lymphoma, or NK-cell enteropathy. In addition, syncytial variant of classical Hodgkin lymphoma or a pleomorphic CD30-positive diffuse large B-cell lymphoma should also be ruled out. We discuss pitfalls of the differential diagnosis and review the literature of anaplastic large cell lymphoma in the gastrointestinal tract. Correct diagnosis of ALCL in the colon is important to avoid a colorectal surgery for an assumed adenocarcinoma, and to open the possibility for lymphoma-directed chemotherapy.

Primary adrenal Epstein–Barr virus‐positive diffuse large B cell lymphoma of the elderly, mimicking pseudocyst

ABSTRACTPrimary adrenal lymphoma is rare, but clinically important. We report a unique case of adrenal lymphoma which showed extensive cystic change mimicking a pseudocyst. Seventy‐three‐year‐old man visited our hospital for healthcare check‐up, and was found to have a large adrenal cystic mass. He was received adrenalectomy on the impression of an adrenal pseudocyst. On gross examination, the mass was a unilocular cyst with no solid mass formation. Microscopically, the cyst wall had no epithelial lining, but was infiltrated by some atypical large lymphoid tumor cells. The cystic space was filled with coagulative necrotic material with the tumor cell shadow. The most of the tumor cells expressed leukocyte common antigen, CD20, PAX5, Ki‐67, and Epstein‐Barr virus (EBV)‐encoded RNA, which was consistent with EBV‐positive diffuse large B‐cell lymphoma of the elderly. No extra‐adrenal involvement was observed in imaging studies. We concluded that primary adrenal lymphoma should be considered as a rare but important cause of adrenal cysts.

Multicentric Castleman Disease with Complete Duodenal Obstruction in an HIV Patient

Abstract 4834Multicentric Castleman's Disease(MCD) can have an aggressive course making early diagnosis and treatment important. Although rare, peripancreatic involvement is known in Castleman's disease and an unusual presentation should be considered especially in the setting of HIV. An excisional lymph node biopsy is required for diagnosis. High plasma titers of Human Herpes Virus 8 DNA should also raise this possibility. Coexistence of Castleman disease and body cavity lymphoma has been reported but is rare. Case Presentation:A 42 year old African American gentleman with a history of HIV and CD4 count 271 presented with intractable nausea and vomiting of 1 month duration; associated with epigastric pain and weight loss. Past history was significant for presentation with jaundice 6 months earlier when he was found to have a pancreatic head mass with portocaval and retroperitoneal lymphadenopathy raising the suspicion of pancreatic adenocarcinoma. Endoscopic ultrasound guided fine needle aspiration of the mass had revealed a poorly differentiated malignant neoplasm that could not be further characterized by immunohistochemistry. Considering the HIV status of the patient, there was a strong suspicion of lymphoma. A PET-CT was planned to identify an appropriate site for tissue diagnosis but the patient was lost to follow up. Repeat imaging during the current admission revealed increasing size of the pancreatic mass causing complete obstruction of second part of duodenum. The patient subsequently underwent gastro-jejunostomy to bypass the duodenal obstruction and an excisional biopsy of two mesenteric lymph nodes was performed during the procedure. Pathology revealed HHV-8 positive plasma cell variant of Castleman's disease. Patient also had high plasma titers of HHV-8. Furthermore, the patient was also found to have bilateral pleural effusions and a thoracentesis was performed. Pleural cytology revealed large plasmablastic lymphoid cells that were positive for HHV-8, CD30, CD45, CD138, Ebstein-Barr virus (EBV), epithelial membrane antigen, and multiple myeloma oncogene-1. These findings suggested a diagnosis of body cavity lymphoma. Discussion:Although rare, the association of Multicentric Castleman's disease (MCD) with HIV is well recognized. The incidence is independent of CD4 count and the use of HAART. There are isolated case reports of pancreatic involvement with Castleman's disease and only one involving the duodenum. While most patients with peripancreatic involvement presented with abdominal discomfort, nausea or systemic symptoms, our patient was severely symptomatic from complete duodenal obstruction. Our case also highlights that the diagnosis can be elusive and requires excisional lymph node biopsy. Moreover, HIV MCD is fluorodeoxyglucose avid, and a PET-CT may help identify the gland to biopsy next in difficult to diagnose cases. Body cavity lymphoma is also HHV-8 related and this diagnosis should be considered in any HIV patient with effusions. Pleural fluid cytology and immunohistochemistry usually clinch the diagnosis. Disclosures:No relevant conflicts of interest to declare.

Primary Ovarian Lymphoma: A Case Report and Review of Literature

Primary Ovarian Lymphoma: A Case Report and Review of Literature

A Rare Case of Colorectal Peripheral T-Cell Lymphoma Associated with Mycosis Fungoides

Purpose: ‘Mycosis Fungoides' (MF) is an indolent T cell lymphoma, involving primarily skin with rare extracutaneous, or visceral involvement occurring in advanced stages of the disease. Gastrointestinal system involvement is very rare and it is associated with significant morbidity and mortality secondary to various complications. We are describing a case of “Peripheral T-Cell Lymphoma” involving the rectum and the colon diagnosed on a screening colonoscopy in a patient with a history of Mycosis Fungoides. A 66-year-old AA man with h/o of HTN, dyslipidemia, and mycosis fungoides was referred by his dermatologist for a screening colonoscopy. He denied any symptoms including weight loss, rectal bleeding, melena, hematemesis or altered bowel movements. His physical exam was notable for diffuse hypopigmented and hyperpigmented patches over the skin, primarily hands and feet. There was no evidence of splenomegaly or lymphadenopathy. He was lost to follow up for five years after a decade of stable disease. He was started on clobetasol topical ointment and narrow band UVB therapy. Colonoscopy showed a large ulcerated mass with greenish black exudate occupying 50-74% of the circumference of the rectum, extending 5cm from entry site up to 17cm. The biopsy showed colonic mucosa diffusely infiltrated by large atypical lymphoid cells with varied size, hyperchromatic nuclei and small nucleoli. Flow cytometry showed abnormal clonal T cell proliferation and stained positive for CD3, CD4, CD5 and rarely for CD8 suggestive of peripheral T cell lymphoma. A molecular study for TCR Gamma rearrangement performed on the previous lymph node biopsy and the current rectal specimen showed identical clonal peaks indicating that the process in the rectum likely represents transformation of the patient's cutaneous T cell lymphoma. A month later, he was admitted to the hospital with severe pain and swelling in his right lower extremity. He was found to be having a diffuse systemic involvement of T cell lymphoma of plural fluid, right thigh, inguinal lymphnodes, and CNS. His prognosis was assessed to be very poor and he was sent to hospice care based on his wishes for comfort care.Figure: No Caption available.

Intravascular large B cell lymphoma presenting as anasarca: an unusual presentation of a rare lymphoma

Dear Editor, An 82-year-old male presented with progressive generalized edema over a month without associated fever, angina, dyspnea, rash, lymphadenopathy, and neurological or gastrointestinal symptoms. He was found to be profoundly hypotensive requiring vasopressor support. Initial blood work revealed severe hypoalbuminemia of 1.6 g/dL and a markedly elevated LDH of 1891 U/L. Complete blood count revealed normocytic anemia with hemoglobin of 9.8 g/dL and normal platelet and leukocyte count. Peripheral smear showed no abnormal cells. Liver function tests, urinalysis, chest X-ray, and echocardiogram were unremarkable. Random skin biopsies were subsequently performed revealing intravascular infiltration of CD5and CD20-positive malignant cells compatible with intravascular B cell lymphoma (IVLBCL; Fig. 1). IVLBCL is a rare malignancy with estimated incidence of less than one per million per year [1]. It was first described as endothelial cell tumor [2]. Subsequent immunohistochemical studies confirmed its lymphoidal nature [3]. In 2008, WHO classified IVLBCL as a subtype of extranodal diffuse large B cell lymphoma characterized by limited proliferation of lymphoma cell within lumina of small blood vessels [4]. Diagnosis of IVLBCL can be challenging given its bewildering presentation. Virtually, any organ can be affected as a result of small vessel occlusion. Fever, night sweat, and weight loss are the most common presentation. In western countries, these constitutional symptoms are frequently accompanied by neurological and cutaneous symptoms, whereas hemophagocytic syndrome is more predominant in Asian population [1, 5]. Anarsarca is an unusual initial presentation and was found in less than 5 % in one case series [5]. Biopsy is mandatory for the diagnosis. Involved tissues demonstrate large lymphoid cells with prominent nucleoli and frequent mitotic figures in the capillaries and venules. B cell-associated antigens, particularly CD20, CD5, and CD10, are typically positive. Selection of organ for biopsy should be guided by patient's manifestation as identification of tumor cells is relatively easy when an affected organ is biopsied [6]. In case of no apparent specific organ involvement, as seen in our patient, random skin biopsy from normal-appearing skin is an alternative diagnostic approach with a high sensitivity of 83.3 % [7]. Prognosis of a patient with IVLBCL is unfavorable although recent retrospective studies suggest more promising outcome with the use of rituximab in conjunction with anthracycline-based chemotherapy [1, 8]. Our patient, with unstable hemodynamics despite of vigorous resuscitation, was not a suitable candidate for instituting chemotherapy. Unfortunately, his clinical course deteriorated and he passed away after a week of hospitalization.

Primary T-cell lymphoma associated with tubulovillous adenoma of the rectum: report of a case

We report what to our knowledge is the first documented case of "peripheral T-cell lymphoma-not otherwise specified" (PTCL-NOS) associated with a rectal adenoma. Colorectal lymphomas are relatively uncommon, but colorectal T-cell lymphomas are extremely rare. The patient was a 92-year-old woman, referred to our hospital for investigation of anal bleeding. Rectal examination revealed a 3-cm pedunculated polypoid mass 5cm above the anal verge. We performed a transanal local excision, and histopathological examination revealed a tubulovillous adenoma, with the diffuse proliferation of large lymphoid cells mainly discernible in the mucus membrane lamina propria, with infiltration to the submucosal layer. Immunohistochemical examination of the lymphoid cells revealed positive staining for CD3, weak staining for CD4 and CD8, and negative staining for CD5, CD10, CD20, CD56, CD79a, TIA-1, and Granzyme B. The tumor was diagnosed as PTCL-NOS associated with rectal tubulovillous adenoma. The patient died 28days after surgery, most probably of progression of the PTCL-NOS.

Diffuse variant of lymphocyte-predominant Hodgkin lymphoma: a diagnostic challenge

The diffuse variant of nodular lymphocyte-predominant Hodgkin lymphoma (D-LPHL) is exceedingly rare. Here we report a case of D-LPHL in a 35-year-old Caucasian female who presented with left cervical and right axillary lymphadenopathy. Histopathologic examination reveals large atypical lymphoid cells resembling lymphocyte-predominant (LP) cells in a background of reactive T cells, B cells, and histiocytes. Extensive immunohistochemical study demonstrates that these large atypical lymphoid cells express characteristic phenotype of LP cells including CD20, CD79a, BOB-1, OCT-2, BCL-6, and EMA and are negative for CD30 and fascin. The diffuse nature of the lymphoid proliferation is confirmed by negative CD21, CD23, and CD35 stains showing a complete lack of follicular dendritic cell meshworks. The associated T cell microenvironment shows increased CD57(+) T cells arranged into peritumoral cell rosettes. The diagnostic criteria of this case are discussed and a review of the literature about the differential diagnosis is provided.

Diffuse large B-cell lymphoma presenting with neurolymphomatosis and intravascular lymphoma: a unique autopsy case with diverse neurological symptoms

A 78-year-old Japanese male noticed a difficulty in the beginning of standing up, followed by 7a progressive numbness of extremities with pain, Bell’s palsy, dysarthria, and difficulty in swallowing. A clinician had suspected cancer of unknown primary origin, accompanied by the diverse and elusive neurological symptoms, likely presenting as painful mononeuropathy simplex and cranial neuropathy. He developed dysbasia over weeks and died 1 month after the symptom onset. At autopsy, an ill-defined large and soft tumor mass in the right lobe of the liver with direct invasion into the right adrenal gland was observed. The left adrenal gland or right iliopsoas muscle was also involved. Microscopic findings showed a monotonous proliferation of medium-sized to large atypical lymphoid cells, which were diffusely positive for CD20 in immunohistochemistry, consistent with diffuse large B-cell lymphoma (DLBL). Furthermore, the lymphoma cells aggressively infiltrated endoneurial and subperineurial spaces not only in the peripheral nerves and plexuses, but partly in the spinal nerve roots, and intravascular spaces in various tissues. Therefore, systemic lymphoma (DLBL) complicated with neurolymphomatosis (NL) and intravascular lymphoma (IVL) was diagnosed. Very early diagnosis and treatment are necessary for the NL patients with poor prognosis.Virtual slidesThe virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5862472377020448.

A Case of Age-Related Epstein–Barr Virus (EBV)-Associated B Cell Lymphoproliferative Disorder, so-called Polymorphous Subtype, of the Mandible, with a Review of the Literature

Epstein-Barr virus (EBV) is known to be associated with the development of lymphomas in immunocompromised patients. Recently, age-related immune impairment has been recognized as a predisposing factor in the development of EBV-driven lymphoproliferative disorders (LPDs) in elderly patients without any known immunodeficiency or prior lymphoma. In approximately 70% of reported cases, the affected sites have been extranodal, such as the skin, lung, tonsil and stomach. However, age-related EBV-associated B cell (EBV + B cell) LPD is extremely rare in the oral cavity. Here we report a 71-year-old Japanese man who developed an EBV + B cell LPD resembling classical Hodgkin lymphoma (CHL)--so-called polymorphous subtype-of the mandible. Histopathologically, infiltration of large atypical lymphoid cells including Hodgkin or Reed-Sternberg-like cells into granulation tissue with marked necrosis was found in the mandibular bone. Immunohistochemical analysis revealed that the large atypical Hodgkin or Reed-Sternberg-like cells were CD3-, CD15-, CD20+, CD30+ and Epstein-Barr virus (EBV)-latent infection membrane protein-1 (LMP-1)+. In situ hybridization (ISH) demonstrated EBV-encoded small RNA (EBER) + in numerous Hodgkin or Reed-Sternberg-like cells. EBNA-2 was detected by polymerase chain reaction (PCR) using an extract from the formalin-fixed, paraffin-embedded specimen. To our knowledge, this is the first reported case of the polymorphous subtype of age-related EBV + B cell LPD affecting the mandible.