Nodular lymphocyte-predominant hodgkin lymphoma or T-cell/histiocyte rich large B-cell lymphoma: the problem in "grey zone" lymphomas

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare indolent B-cell lymphoma. However, its morphology can resemble T-cell/histiocyte rich large B-cell lymphoma (T/HRBCL), a subtype of more aggressive diffuse large B-cell lymphoma. More and more studies suggest that these two entities are closely related. In this report, a 59-year-old man with nodal NLPHL and concomitant T/HRBCL in the bone marrow is presented, the current progress in our understanding of these two closely related B-cell lymphomas reviewed and the problems in the diagnosis and differentiation of NLPHL and T/HRBCL discussed.     

Intravascular large B-cell lymphoma confirmed by lung biopsy

Intravascular lymphoma is a very rare form of large B-cell non-Hodgkin’s lymphoma which is characterized by selective growth of lymphoma cells within the lumina of small blood vessels. We report a 64-year-old woman visited hospital because of persistent cough, intermittent high fever as high as 38.7°C and occasional shortness of breath. Her chest CT showed left upper lobe pneumonia and tuberculosis skin test (PPD test) was positive. She was suspected with tuberculosis and treated with anti-tuberculosis drugs. However, her symptoms and general condition deteriorated, and she visited our hospital. She had no abnormal findings on physical examination, but had abnormal laboratory findings, including decreased hemoglobin, elevated LDH and C-reactive protein. Arterial blood gas analysis showed moderate hypoxaemia. A chest radiograph showed pneumonia in whole lung and CT showed diffused ground glass opacities in both lung fields. Lung biopsy confirmed a diagnosis of intravascular large B-cell lymphoma. Primary pulmonary manifestation is very rare. The diagnosis is based on the histopathology and immunohistochemistry.     

Recurrent diffuse large B-cell lymphoma presenting initially as hemophagocytic syndrome

Hemophagocytic syndrome (HPS) is an extremely rare and life-threatening abnormality, and the cases secondary to B cell lymphoma are rare. We report a case of relapsed diffuse large B-cell lymphoma initially presenting with hemophagocytic syndrome. The patient developed multiple erythematous macules and progressive thrombocytopenia during the treatment, and died two weeks after admission. The HPS presented as an initial manifestation of the relapsed diffuse B-cell lymphoma and the maculea that appeared during the treatment might be a strong predictor of unfavorable outcome.     

Composite diffuse large B-cell lymphoma and CD20-positive peripheral T-cell lymphoma

Composite lymphoma is defined as two or more distinct types of lymphoma in a single anatomical site. Among various combinations, composite B-cell and T-cell non-Hodgkin's lymphomas (CBTL) are very infrequent. Herein we describe a 66-year-old female with CBTL presenting with lymphadenopathy, multiple bone lesions and an epidural tumor. Light microscopic examination of a biopsied cervical node revealed a dual population of lymphoid cells: sheets of large cells admixed with medium-sized cells. The large cells expressed B-cell markers and showed immunoglobulin light chain restriction, consistent with diffuse large B-cell lymphoma (DLBCL). The medium-sized cells were positive for CD20 as well as T-cell markers. Because polymerase chain reaction amplification showed monoclonal rearrangement of the T-cell receptor β chain gene, this population was compatible with peripheral T-cell lymphoma not otherwise specified (PTCL-NOS). We therefore made a diagnosis of composite DLBCL and CD20-positive PTCL-NOS. Complete remission was achieved after six cycles of R-CHOP regimen (rituximab, doxorubicin, vincristine, cyclophosphamide and prednisolone). This is the first report of CD20-positive PTCL-NOS associated with composite lymphoma. Moreover, a literature review of composite DLBCL and PTCL-NOS indicates that this rare clinical entity may be featured by efficacy of systemic chemotherapy in spite of prevalent extranodal lesions.     

A case of primary unilateral adrenal Burkitt-like large cell lymphoma presenting as adrenal insufficiency

Primary adrenal lymphoma is extraordinarily rare, in comparison with secondary adrenal involvement by non-Hodgkin lymphoma. Although higher-resolution imaging techniques have enhanced detection of adrenal masses, biopsy or excision is often needed for definitive diagnosis. Percutaneous computed tomography-guided fine needle aspiration has great diagnostic value in the workup of adrenal masses, but is limited by sampling error and artifacts. Primary adrenal lymphoma most commonly manifests with diffuse large B-cell morphology. Burkitt-like large cell lymphoma morphology has been previously reported only once, to our knowledge. We report an 80-year-old man presenting with unilateral primary adrenal lymphoma showing Burkitt-like morphology and adrenal insufficiency. Fine needle aspiration yielded a dispersed population of monomorphic, medium to large cells suggestive of lymphoma. Although dispersed cell populations cytologically favor lymphoma, metastatic poorly differentiated carcinoma and adrenal cortical carcinoma can manifest similarly. Integrated histological, immunohistochemical, and flow cytometric immunophenotyping would provide an accurate and definitive diagnosis. We review the literature and discuss important issues with regard to diagnosis.     

Intravaskuläres Lymphom als Ursache für akutes Abdomen

A 65-year old man presented with acute abdominal pain and fever. The initial diagnosis was small bowel gangrene. Pathology revealed small to large abdominal vessels obliterated by cells of intravascular B-cell-lymphoma (IVL). Visceral IVL involvement is common at autopsy but rarely reported in patients with acute abdomen. The subtype of diffuse large B-cell lymphoma is a rare and aggressive malignancy, which in typical cases is characterized by cephalic or cutaneous manifestation. Few cases showed involvement of large vessels which in combination to fibrin thrombi may lead to infarction of the organ involved. Thus IVL should be considered in cases of ischemic diseases with fever of unknown origin.     

Lung intravascular large B-cell lymphoma with ground glass opacities on chest computed tomography: a case report

Intravascular large B-cell lymphoma (IVLBCL) is a rare type of extranodal large B-cell lymphoma characterized by the selective growth of lymphoma cells within the lumina of vessels, particularly within capillaries, with exception of larger arteries and veins. The authors reported a case of a 45-year-old woman who was admitted in hospital with refractory fever, cough and progressive dyspnea despite of receiving broad-spectrum antibiotics. Computed tomography (CT) of the lung showed bilateral patchy ground-glass opacities with some pleural effusion in the left lung. A CT-guided percutaneous lung biopsy was performed and primary pulmonary intravascular large B-cell lymphoma was diagnosed by histopathology, immunophenotype and fluorescence in situ hybridization. The patient’s general status was improved after chemotherapy with R-CHOP. CT-guided percutaneous biopsy of lung is a safe and accurate diagnostic procedure in IVLBCL.     

Primary non-Hodgkin's lymphoma and malakoplakia of the vagina: a case report.

The vagina is a rare site for both primary non-Hodgkin's lymphoma and malakoplakia. We report a case of concurrent diffuse large B-cell lymphoma and malakoplakia of the vagina in a 67-year-old woman presenting with a vaginal discharge and a vaginal mass. The patient had two biopsy specimens reported as showing malakoplakia only, followed by a third biopsy specimen 10 months later which was diagnosed as diffuse large B-cell lymphoma. Review of the first two biopsy specimens showed areas of histiocytes with Michaelis-Gutman bodies merging with areas of cells with slightly larger nuclei and more amphophilic cytoplasm. Immunohistochemistry for the B-cell marker L-26 (CD20) and polymerase chain reaction analysis of the immunoglobulin heavy chain gene were helpful in retrospectively distinguishing the population of diffuse large B-cell lymphoma from the areas of malakoplakia. The third biopsy specimen showed sheets of large atypical lymphoid cells characteristic of a large cell lymphoma. Malakoplakia has been described in association with a variety of cancers, and this is only the second report of malakoplakia associated with non-Hodgkin's lymphoma. Considering the rarity of these two entities in the vagina, it is unlikely that the association in this case is coincidental, raising the possibilities of an unusual reaction to the presence of lymphoma or a common pathogenesis such as underlying chronic inflammation. Epstein-Barr virus DNA was detected in the second biopsy specimen, suggesting a possible role in the pathogenesis of this lymphoma.     

Testicular ischemia due to intravascular large B-cell lymphoma: a novel presentation in an immunosuppressed individual

A 56-year-old man presented with fever, disorientation, and testicular pain. He was receiving azathioprine immunosuppression for autoimmune hepatitis. Orchiectomy identified occlusion of spermatic cord vessels by intravascular large B-cell lymphoma (IVLBL) and ischemic changes in the testis. Tumor cells were positive for CD 10, CD 20, CD 30, and Epstein-Barr virus (EBV) latent membrane protein 1 (LMP-1) and early region RNA (EBER). He was treated with the cessation of azathioprine, chemotherapy, anti-CD 20 immunotherapy, and radiotherapy. Twenty months after diagnosis, he is alive with no evidence of lymphoma or hepatitis. This is the first report of IVLBL presenting with testicular ischemia. It highlights the importance of prompt diagnosis and intervention to achieve durable response. That this lymphoma arose in the setting of immunosuppressive therapy introduces additional complexity relating to pathogenesis, clinical behavior, and treatment.     

Intravascular large B-cell lymphoma presenting as cholecystitis and pancytopenia: case report with literature review

Intravascular large B-cell lymphoma (IVLBCL) is a rare variant of extranodal diffuse large Bcell lymphoma with only a few more than 300 cases reported. It is characterized as lymphoma cells confined to the lumina of small vessels, so patients usually do not present with masses or lymphadenopathy. Clinical presentations of these patients are non-specific and the pathologic changes may be subtle, which often leads to delayed diagnoses and, in many instances, a postmortem diagnosis. IVLBCL can essentially involve the vessels of any organ, but it is quite rare for the gallbladder to serve as the initial presenting site; there are only four such cases reported in the English literature. Furthermore, IVLBCL of the gallbladder with peripheral blood involvement is even less common. We report a recent case of IVLBCL presenting as acute cholecystitis and pancytopenia. The patient underwent a simple cholecystectomy. Examination of the gallbladder showed clusters of large lymphoma cells within lumina of small vessels in the gallbladder wall. These cells were positive for CD5/CD20 and negative for CD3, CD10, and TdT. Based on these findings, a diagnosis of IVLBCL was made. Coincidently, circulating lymphoma cells were identified in the peripheral blood and confirmed by flow cytometric analysis (positive for CD19/CD20/CD5, without light chain expression). The patient was started on chemotherapy but subsequently died of chemotherapy related multi-organ failure 10 days after the initial diagnosis.     

Peripheral T-cell lymphoma presenting as a soft-tissue mass of the extremity

An 87-year-old man was found to have a lymphoma in the deep soft tissue of the right shoulder with concomitant central nervous system involvement. There was no evidence of cutaneous, peripheral lymph node, mediastinal, abdominal, or bone marrow involvement. Light microscopic, ultrastructural, and immunohistochemical evaluation characterized the neoplasm as a peripheral T-cell lymphoma. Lymphomas presenting in soft tissue are rare, and the few well-documented cases in the literature are of B-cell origin. We report a T-cell lymphoma presenting in the soft tissue of the extremity, and delineate its clinicopathologic features.     

Genomic Analysis Reveals Distinct Subtypes in Two Rare Cases of Primary Ovarian Lymphoma

Primary (localized) non-Hodgkin lymphoma (NHL) of the ovary is extremely rare; only a few cases have been reported in the literature. We report two cases of primary ovarian lymphoma (POL), one involving bilateral ovaries in a 15-year-old girl and other involving one ovary in a 5-year-old girl. This report describes detailed clinical, histopathological, and imaging findings, along with the review of literature of primary diffuse large B-cell lymphoma (DLBCL) arising from an ovary. In addition, we describe findings of targeted capture panel sequencing on both tumors and identify the major genetic mutations that are recurrently mutated in pan-cancers. Compared to the genomic mutation features of major subtypes of DLBCL, we distinguish that each POL belongs to distinctive subtypes, GCB (germinal center B-cell subtype) DLBCL and ABC (activated B-cell subtype) DLBCL, respectively. The findings from the genomic analysis may help to understand the pathogenesis of POL and to guide potential targeted therapy in the future.     

Prostate involvement by intravascular large B-cell lymphoma: a case report with literature review

Prostate involvement by intravascular large B-cell lymphoma (IVLBL) is extremely rare. Until now, only 6 cases have been reported in the literature. In this article, the authors report a case of a 65-year-old Chinese man with IVLBL located in the prostate. The diagnosis of IVLBL was obtained incidentally from a biopsy of his prostatectomy specimen. The patient underwent CHOP therapy for 5 cycles and had a favorable clinical outcome.     

Intravascular large B-cell lymphoma with bone marrow involvement at presentation and haemophagocytic syndrome: two Western cases in favour of a specific variant

AIMS: To report two cases of an unusual form of intravascular lymphoma, characterized by bone marrow involvement at presentation with haemophagocytic syndrome. METHODS AND RESULTS: We describe the clinicopathological features of two patients with intravascular lymphoma primarily involving bone marrow. Both patients complained only of fever with pancytopenia and reactive haemophagocytic syndrome. Diagnosis was made on bone marrow examination, which showed large tumour cells of B-cell lineage confined within the lumen of sinuses. CONCLUSION: These two cases and five previous reports could represent a variant of intravascular lymphoma, characterized by early involvement of bone marrow without dissemination to other organs. This form of intravascular lymphoma, called IVL-HS, seems to be an 'Asian' variant with a high prevalence in Asian people and a very low prevalence in Western countries. At a practical level, bone marrow biopsy may be useful in the diagnosis of intravascular lymphoma when the clinical presentation is restricted to fever of unknown origin with a reactive haemophagocytic syndrome.     

T-cell-rich B-cell lymphoma (TCRBCL): limitations in fine-needle aspiration cytodiagnosis

Exclusive reports on fine needle aspiration (FNA) cytodiagnosis of T-cell-rich B-cell lymphoma (TCRBCL) are scarce in literature. This report reflects the diagnostic difficulties associated with cytodiagnosis of this rare variant of diffuse large B-cell lymphoma. The study is based on 11 cases with age ranging from 16 to 63 years and a median of 50 years. Male to female ratio was 6:5. Ten cases presented with lymphadenopathy and one had lymphadenopathy as well as extranodal solid tumor. The initial cytodiagnosis was suggestive of TCRBCL in one case, TCRBCL/Hodgkin's lymphoma (HL) in three cases, TCRBCL/HL/anaplastic large cell lymphoma (ALCL) in two cases, TCRBCL/ALCL in one case, and TCRBCL/non-Hodgkin lymphoma (NHL) T-cell/ALCL in one case. There was also a cytologically diagnosed HL case, which on review turned out to be HL/TCRBCL. Histopathological diagnosis was HL in all these nine cases. There were two histologically diagnosed TCRBCL cases during this period, with cytodiagnoses of NHL other than TCRBCL in one and HL in the other. While highlighting the difficulties associated with the cytodiagnosis of TCRBCL, this study conveys a word of caution that adequate immunocytochemical studies should be performed before diagnosing this rare neoplasm with a varied cytomorphology.     

Fever of unknown origin characterized by acute kidney injury and nephrotic syndrome diagnosed as intravascular large B-cell lymphoma of kidney: case report and literature review

A 60-year-old Chinese female patient was admitted to the hospital with complaint of intermittent fever for more than seven months. The main clinical manifestations were acute kidney injury and nephrotic syndrome which developed into a hemophagocytic syndrome. The symptoms did not improve with antibiotics. Moreover, prednisone could only reduce the fever. Finally, a kidney biopsy showed many CD20-positive cells in the glomerulus and some in the peritubular capillaries. This led to a diagnosis of renal intravascular large B-cell lymphoma.     

Intravascular large B-cell lymphoma

A rare type of diffuse large B-cell lymphoma, intravascular large B-cell lymphoma primarily affects the middle-aged to elderly population, with a slight predominance in men. By the time of presentation, most patients have advanced, disseminated disease, and often the diagnosis is made at autopsy. Patients may present with any of a myriad of symptoms, with any tissue potentially being infiltrated. Central nervous system and cutaneous involvement is common, as is the presence of B symptoms including fever, weight loss, and night sweats. Morphologically, growth of neoplastic cells is restricted to the lumen of small vessels. The cells are large, with 1 or more prominent nucleoli, scant cytoplasm, and frequent mitotic figures, and are commonly positive for cluster of differentiation markers 79a, 20, and 19, as well as MUM1/IRF4 and Bcl-2. Intravascular large B-cell lymphoma is aggressive, and without treatment is rapidly fatal.     

Non-Hodgkin's lymphoma of the breast: a review of 18 primary and secondary cases

We evaluated the clinical features, morphology, and incidence of 18 cases of breast lymphoma over 10 years at the University of Alabama at Birmingham. Fine needle aspiration was performed in 7 of 18 patients, and tissue biopsy/resection was available for all 18 cases. Patients were 33 to 91 years old (median, 61); 17 were women and 1 was a man. Fine needle aspiration was consistent with the tissue diagnosis in 6 of the 7 cases (86%). One case was diagnosed by fine needle aspiration as atypical cells, favor benign; the biopsy revealed diffuse large B-cell lymphoma. Tissue diagnoses revealed that 11 cases (61%) represented diffuse large B-cell lymphoma and 3 (17%) were follicular lymphomas. The remaining 4 cases (22%) were plasma cell neoplasm, T-cell neoplasm, Burkitt's lymphoma, and precursor B-cell lymphoblastic lymphoma. Flow cytometry and/or gene rearrangement supported the diagnosis of lymphoma in 8 cases. Although rare, lymphoma should be considered in the differential diagnosis of a breast mass. Fine needle aspiration can facilitate appropriate triage of patients for further management.     

B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma without mediastinal disease: mimicking nodular sclerosis classical Hodgkin lymphoma

B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma (BCLu-DLBCL/CHL), also known as gray-zone lymphoma, has overlapping clinical and biological characteristics of both diffuse large B-cell lymphoma and classical Hodgkin lymphoma (CHL). These lymphomas are typically associated with mediastinal disease, and extranodal involvement is rare. In the present report, we describe a case of a 78-year-old woman with BCLu-DLBCL/CHL found to have extranodal lesions and no evidence of mediastinal disease. Although biopsy specimens were histologically similar to nodular sclerosis CHL, the tumor cells were positive for CD30 and mature B-cell markers, such as CD20, CD79a, PAX5, BOB.1, and OCT-2, but negative for CD15. Furthermore, the patient had extranodal lesions and an increased level of soluble IL-2 receptor. These findings are unusual in CHL. Therefore, we diagnosed the patient with BCLu-DLBCL/CHL. She received adriamycin, bleomycin, vincristine, and dacarbazine therapy and exhibited partial response. Some cases without mediastinal disease, such as our case, have been reported; however, these cases are rare and further studies are required.     

Intravascular large B-cell lymphoma involving hemangiomas: an unusual presentation of a rare neoplasm.

We report the clinicopathological features of two cases of intravascular large B-cell lymphoma involving cutaneous hemangiomas. The cases were identified from the consultation files of two of the authors. Both patients were women, 64 and 55 years of age, who presented with long-standing cutaneous hemangiomas of the posterior scalp and left shoulder, respectively. The lesions were brought to medical attention by an increase in size and change in color. Biopsies and immunohistochemical evaluation of the hemangiomas revealed extensive involvement by intravascular large B-cell lymphoma. The neoplastic cells were diffusely positive for CD20 in both cases and negative for CD3, pan-cytokeratin (AE1/AE3), epithelial membrane antigen, S-100, Factor VIII-related antigen, CD34 and CD31. Disease was limited to the hemangiomas in both patients. Treatment consisted of chemotherapy (both patients) and adjuvant radiation therapy (one patient). One patient had a recurrence of disease 33 months after initial diagnosis, leading to an autologous stem cell transplant. The other patient is without evidence of disease 27 months after initial diagnosis. Although this is a rare neoplasm, it is important to consider intravascular large B-cell lymphoma in the differential diagnosis of vascular lesions containing intravascular neoplastic cells.