Diffuse Large B-cell Lymphoma Presenting Research Articles

Intraosseous diffuse large B-cell lymphoma presenting as fracture of humerus

Non-Hodgkin's lymphomas (NHL) is the most common primary bone lymphoid malignancy, and diffuse large B-cell lymphoma (DLBCL) accounts for the greatest percentage of cases. Here we report a 34-year-old male presented with pain and swelling of left shoulder joint of 2-month duration. There was no history of trauma. A diagnosis of intraosseous NHL-Diffuse large B-cell lymphoma (DLBCL) was made. He was treated with six cycles of with R-CHOP (Rituximab, Cyclophosphamide, Vincristine, Doxorubicin and Prednisolone) chemotherapy. Our report suggests that primary intraosseous high-grade NHL, e.g. DLBCL can present as fracture in an unusual site in a young adult.

Pituitary and adrenal involvement in diffuse large B-cell lymphoma, with recovery of their function after chemotherapy

BackgroundDiffuse large B-cell lymphoma sometimes involves the endocrine organs, but involvement of both the pituitary and adrenal glands is extremely rare. Involvement of these structures can lead to hypopituitarism and adrenal insufficiency, and subsequent recovery of their function is rarely seen. The present report describes an extremely rare case of pituitary and adrenal diffuse large B-cell lymphoma presenting with hypopituitarism and adrenal insufficiency with subsequent recovery of pituitary and adrenal function after successful treatment of the lymphoma.Case presentationA 63-year-old Japanese man was referred to our hospital due to miosis, ptosis, hypohidrosis of his left face, polydipsia and polyuria. 18F-fluorodeoxy glucose positron emission tomography / computed tomography revealed hotspots in the pituitary gland, bilateral adrenal glands and the apex of his left lung. Surgical biopsy from the pituitary lesion confirmed the diagnosis of diffuse large B-cell lymphoma, with lymphoma cells replacing normal pituitary tissue. Endocrine function tests revealed adrenal insufficiency and panhypopituitarism, including a possible affection of the posterior pituitary. Hormone replacement therapy with desmopressin and hydrocortisone was started. Chemotherapy consisted of six courses of R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin and prednisolone) and two courses of high-dose methotrexate followed by autologous hematopoietic stem cell transplantation. Subsequently, his pituitary and bilateral adrenal lesions resolved, and serial endocrine function tests showed gradual improvement in pituitary and adrenal function.ConclusionsThe present report describes an extremely rare case of diffuse large B-cell lymphoma with involvement of both the pituitary and bilateral adrenal glands. R-CHOP and high-dose methotrexate therapy followed by autologous hematopoietic stem cell transplantation was quite effective, and panhypopituitarism and adrenal insufficiency improved to almost normal values after successful treatment of the lymphoma with chemotherapy.

An Epstein–Barr virus-positive diffuse large B-cell lymphoma presenting as multi-organ failure: A catastrophic lymphomatosis with fulminant visceral organ dissemination resulting in a precipitous death in a 59-year-old female with no identifiable etiology for immunodeficiency

Epstein–Barr virus (EBV)-positive diffuse large B-cell lymphoma (EBV+ DLBCL) of the elderly is an aggressive B-cell neoplasm related to age-associated impaired immunity. We report such a case in a 59-year-old woman with a catastrophic disease course. The patient initially presented with fever, fatigue, malaise and weakness over one-week period. Despite empirical treatment with antibiotics and antiviral agents, she subsequently developed multi-organ failure and coagulopathy. Radiographic imaging revealed hepatomegaly, splenomegaly, pleural effusion, and ascites. Her complete blood cell count showed marked leukocytosis, anemia and thrombocytopenia. Morphologic examination of blood smear demonstrated many abnormal plasmacytoid lymphocytes, and flow cytometric analysis detected an intermediate-large mature B-cell population (69%) without detectable surface immunoglobulin. High copy numbers of EBV genome were detected in the blood by PCR. A diagnosis of EBV+ DLBCL, leukemic phase, was made. Despite aggressive treatment and supportive care, the patient succumbed to multi-organ failure one week after initial presentation. Autopsy demonstrated EBV+ DLBCL infiltration in all the organs examined. This case describes an unusual presentation of EBV+ DLBCL and highlights the necessity of pertinent ancillary tests to avoid delay in the diagnosis and treatment.

A Rare Case of Anaplastic Variant of Diffuse Large B-Cell Lymphoma Presenting as a Lung Primary

Primary pulmonary lymphoma is an uncommon neoplastic disorder representing approximately 0.5% to 1% of primary pulmonary malignancies. The vast majority are of low-grade, mucosa-associated lymphoid tissue type. Primary diffuse large B-cell lymphoma of the lung is rare, though cases of the centroblastic and immunoblastic variants have been described. We present herein an interesting case of an 80-year-old man who presented with both respiratory and constitutional symptoms and was found to have a 4.5 cm left hilar mass with bilateral hilar and mediastinal lymphadenopathy on imaging. Endobronchial biopsy revealed an aggressive large cell lymphoma, with scattered large, bizarre-shaped nuclei resembling Reed-Sternberg cells, positive for CD20, PAX5, CD30, and MUM-1, consistent with an anaplastic variant of diffuse large B-cell lymphoma. Imaging showed no evidence of extrathoracic disease. Standard treatment with cyclophosphamide/vincristine/prednisone and rituximab resulted in significant clinical and radiological response and the patient remains in remission 21 months later. To the best of our knowledge, this modified Ann Arbor stage II2E primary pulmonary lymphoma, is the first description in the English literature of anaplastic variant of diffuse large B-cell lymphoma presenting as a lung primary.

Multiple recurrent extra‐medullary relapses of high‐grade diffuse large B‐cell lymphoma presenting in acute leukemic phase

Multiple recurrent extra‐medullary relapses of high‐grade diffuse large B‐cell lymphoma presenting in acute leukemic phase

Primary Retroperitoneal Diffuse Large B-cell Lymphoma Presenting with Numb Chin Syndrome and Painful Ophthalmoplegia

Numb chin syndrome (NCS) and painful ophthalmoplegia (PO) are neurological syndromes associated with the disturbance of certain cranial nerves and their downstream nerves. These syndromes are caused by various diseases, and, in rare cases precede the diagnosis of systemic malignant lymphoma. We herein present the case of a 59-year-old man diagnosed simultaneously with NCS and PO caused by a tumor located around the cavernous sinus and with diffuse large B-cell lymphoma that was identified via biopsy of a large retroperitoneal tumor. He was successfully treated with a standard rituximab-containing chemotherapy combined with high-dose intravenous methotrexate and intrathecal chemotherapy.

Compensatory Asymmetric Hemidiaphragmatic Uptake Secondary to Contralateral Hemidiaphragmatic Paresis

A 59-year-old man with diffuse large B-cell lymphoma presenting as an anterior mediastinal mass underwent PET/CT after 2 cycles of chemotherapy. PET/CT shows moderately increased FDG uptake in a predominantly left prevascular mass, consistent with partially treated lymphoma. The left hemidiaphragm is elevated. PET shows asymmetric uptake along the right hemidiaphragm, which is hypothesized to represent compensatory increased workload related to contralateral left diaphragmatic paresis. The left diaphragmatic paresis is likely caused by phrenic nerve involvement by left prevascular mass.

Diffuse Large B-cell Lymphoma Presenting as Gastrointestinal Bleeding and Breast Mass

Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid neoplasm accounting for approximately 25% of all non-Hodgkin lymphomas (NHLs). The gastrointestinal (GI) tract is the predominant extranodal site involved but the disease can arise in virtually any tissue. Herein, we describe one such case where patient presented with simultaneous involvement of two extranodal sites, namely the upper GI tract and breast. Case Report: A 56-year-old Hispanic female presented with lightheadedness, malaise, dyspnea, palpitations and near syncope. She had night sweats, unquantified weight loss, mild epigastric pain and melena for three weeks prior to admission. In the emergency room, she was afebrile; blood pressure 118/71 and pulse of 108 with orthostatic changes. On examination, there was a left breast mass located in the right upper quadrant (Figure A) and right inguinal lymphadenopathy. Fecal occult blood testing was positive. Hemoglobin was 6.4 with low iron indices. Blood transfusions were given. Upper endoscopy revealed multiple gastric and duodenal ulcers with volcano-like appearance (Figure B). The left breast mass was biopsied. The pathology findings on both the ulcers and breast mass showed DLBCL with high proliferative index. Bone marrow examination was normal. The patient was subsequently started on a chemotherapeutic regimen in view of disseminated DLBCL. Discussion: Patients with DLBCL typically present with a rapidly enlarging symptomatic nodal mass, usually in the neck or abdomen but extranodal extramedullary disease occurs in up to 40% of cases and can be the presenting symptom. In the GI tract, the stomach is most commonly involved (70%) followed by the small bowel, colon, rectum, and esophagus. Our case was unusual in that there were two extranodal sites involved at presentation.Figure: A shows 3.5 cms left breast mass located in the right upper quadrant; Figure B shows gastric ulcers with volcano-like appearance.

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.

OR33 Secondary pancreatic involvement by diffuse large B-cell lymphoma presenting as acute pancreatitis

Despite major therapeutic advances, the rational choice of the most appropriate first-line regimen in newly diagnosed transplant-ineligible multiple myeloma (TIE-MM) is currently undefined.We aimed to identify the most effective first-line treatment for TIE-MM patients.A total of 37 articles, including 34 treatments and 16,681 patients, were included in this Bayesian network meta-analysis. The outcomes of interest were risk ratios (RR) for progression-free survival (PFS) and overall survival (OS).Based on surface under cumulative ranking curve values, daratumumab-bortezomib-melphalan-prednisone (Dara-VMP) and daratumumab-lenalidomide-dexamethasone (Dara-Rd28) showed superiority compared to other combinations regarding 12-, 24-, 36-, and 48-month PFS. Dara-VMP also ranked first for 12-, 24-, 36-, and 48-month OS.Our finding supports the incorporation of daratumumab into first-line regimens. Additionally, these results highlight the relative benefit of incorporating novel agents like monoclonal antibodies, immunomodulatory derivatives, and proteasome inhibitors in combination with the currently existing treatment options.

Primary Diffuse Large B-Cell Lymphoma Presenting as Chronic Otomastoiditis

Primary Diffuse Large B-Cell Lymphoma Presenting as Chronic Otomastoiditis Primary presentation of lymphoma of the middle ear is rare, with only 18 cases being reported in the literature. Diagnosis of middle ear and mastoid tumors may be delayed because symptoms mimic more common otologic conditions. Only after clinical deteriorationdo patients often undergo further workup and evaluation that iscritical to definitive diagnosis. We describe a case of diffuse largeB-cell lymphoma presenting as unresolved chronic otitis media and mastoiditis. Isolated presentation of primary lymphoma in the middle ear and mastoid without associated cranial nerve deficits or vestibular symptoms has rarely been described previously. Even without advanced symptomatology, it is imperative to exclude the possibility of temporal bone malignancy through proper neurotologic examination and appropriate imaging.

Primary Cutaneous Diffuse Large B-Cell Lymphoma (Leg Type) Presenting as Necrotising Fasciitis

Necrotising fasciitis is a rare rapidly progressive, life threatening, soft tissue infection which spreads along fascial planes. We present a patient who was diagnosed with a primary cutaneous Diffuse Large B-Cell Lymphoma (leg type) following initial presentation as probable necrotising fasciitis. Presentation was of a painful swollen leg, septic shock and MRI findings consistent with the clinical signs. Diagnosis of necrotising fasciitis remains challenging and it is often missed in the early stages. Early fascial biopsy and histopathological analysis is useful in cases where the diagnosis is unclear. We feel that this case highlights these important issues and will benefit others in their management of similar cases in the future.

Diffuse large B‐cell lymphoma presenting as miller fisher syndrome

We report a patient with diffuse large B-cell lymphoma (DLBCL) who initially presented as Miller Fisher syndrome (MFS) responsive to high-dose immunoglobulin treatment. Detailed investigations for the recurrence of neurological symptoms revealed DLBCL that was responsive to chemotherapy. DLBCL should be considered in the differential diagnosis of patients with MFS who have worsening of their neurological condition after initial improvement with conventional therapy.

Anaplastic Lymphoma Kinase (ALK)-Positive Diffuse Large B-Cell Lymphoma Presenting with CNS Involvement: A Case Report

Abstract 5225 IntroductionAnaplastic lymphoma kinase (ALK)- positive large B-cell lymphoma is a rare form of large B-cell lymphoma originally described in 19971. Since its initial description, approximately fifty cases have been reported in the literature, none of which describe extranodal involvement of the CNS as we will present below. CaseThe patient is a 30 year old previously healthy male who presented with visual changes described as decreased acuity and headaches. Papilledema was present on exam, but exam was otherwise negative. Imaging showed an enhancing mass posterior to the Torcula Herophili. With the working diagnosis of meningioma, the lesion was embolized and then debulked. Final pathology, however, revealed an ALK-positive large B-cell lymphoma with cytoplasmic granular ALK staining. Immunohistochemistry was positive for CD 138, CD 45, CD 38, CD 4, MUM1, epithelial membrane antigen (EMA) and monoclonal IgA lambda, and negative for CD 20, CD30, CD 3, and CD 8. FISH revealed ALK rearrangement (likely with clathrin, but pending at time of abstract) and c-MYC amplification, but not translocation. Serum immunoglobulins were normal. PET/CT showed skeletal metastasis but no additional visceral disease. DiscussionALK-positive large cell lymphomas described previously show immunoblastic/plasmablastic-like phenotypes (CD138+, CD 45+, CD 20-, and cytoplasmic IgA expression), but are CD30-negative and have uniform EMA expression and ALK translocations, as did our patient. The majority of ALK-positive DLBCL exhibit an ALK translocation with the long arm of the clathrin gene to form t(2;17)(p23;q23)2.ALK-positive large cell tumors typically present nodally, but cases have been reported extranodally in the nasopharynx, tongue, bone, soft tissue, and stomach. There is a 3:1 male predominance and a poor overall prognosis with a median survival of 12.2 months, with isolated cases having longer survival. Most patients were treated with CHOP-based regimens with or without radiation therapy2,3. The need for more intense or biologically directed therapy in these cases, including early intensification with or without autologous stem cell rescue is recognized. Gambacorti-Passerini and Poglinani recently described lymphoma sensitivity with crizotinib, an anaplastic lymphoma tyrosine kinase inhibitor, in relapsed anaplastic large cell lymphoma after standard treatment with promising results. Investigation into the use of crizotinib in ALK-positive large cell lymphomas as salvage therapy is potentially warranted4.This case presents an interesting treatment dilemma given the ALK mutation, c-myc amplification, and CNS disease. Crizotinib is likely not a salvage option for this patient given unclear CNS availability and the possibility of this tumor being motivated by c-myc as well as ALK. Disclosures:No relevant conflicts of interest to declare.

Diffuse Large B-Cell Lymphoma Presenting as Recurrent Pancreatitis and Obstructive Jaundice

Diffuse Large B-Cell Lymphoma Presenting as Recurrent Pancreatitis and Obstructive Jaundice

Extranodal Diffuse Large B-Cell Lymphoma Presenting as Ileocolic Intussusception in Adolescent

Intussusception is a common cause of abdominal pain in infants and children. Although most cases are idiopathic, about 10% of cases have a pathologic lead point, especially in elderly patients. Diffuse large B-cell lymphoma is not a common etiology of intestinal intussusception, and is a particularly rare etiology of intestinal intussusception in adolescent. We report a case in a 17-year-old adolescent who initially presented with ileocolic intussusception that mimicked acute appendicitis. Exploratory laparotomy disclosed ileocecal diffuse large B-cell lymphoma as the pathological lead point. This case shows that the age of the patient and anatomic location of the intussusception have an important relationship to the etiology of this disease.

T-Cell-Rich Diffuse Large B-cell Lymphoma Presenting as an Intraosseous Maxillary Neoplasm

ABSTRACT Non-Hodgkin lymphomas are a group of highly diverse malignancies with great tendency to affect organs and tissues that do not ordinarily contain lymphoid cells. T-cell/histiocyte-rich large B-cell lymphoma (TCRBCL) is an uncommon histological variant of large B-cell non- Hodgkin lymphoma, morphologically characterized by a minor population of clonal B-cells distributed in a background of prominent reactive T lymphocytes. This is an interesting case of extranodal isolated TCRBCL in jaw bone and to our knowledge this is the first report of its kind in a nonimmune compromised 40-year-old female. An increase in the number of case reports of non-Hodgkin lymphoma in head and neck region definitely makes it to be included as differential diagnosis. The patient has completed 5 years of therapy with no evidence of recurrence.

Localized, Splenic, Diffuse Large B-Cell Lymphoma Presenting with Hypersplenism: Risk and Benefit of Splenectomy

Herein we report a case of a localized, massive, diffuse large B-cell splenic lymphoma diagnosed by splenectomy. A 57-year-old man complaining of weight loss and abdominal pain, was admitted to our hospital. Enhanced computed tomography scanning showed an irregularly enhanced effect in the spleen suggesting a diffuse splenic tumor. Splenectomy was done and the operation progressed without severe complications. The resected spleen weighed 3,500 g. After the operation, the patient recovered from the pancytopenia and pathology diagnosed diffuse large B-cell lymphoma. Standard CHOP plus rituximab chemotherapy was given. Complete remission has continued for 30 months.

Heat stress triggers apoptosis by impairing NF-κB survival signaling in malignant B cells

Nuclear factor-kappaB (NF-kappaB) is involved in multiple aspects of oncogenesis and controls cancer cell survival by promoting anti-apoptotic gene expression. The constitutive activation of NF-kappaB in several types of cancers, including hematological malignancies, has been implicated in the resistance to chemo- and radiation therapy. We have previously reported that cytokine- or virus-induced NF-kappaB activation is inhibited by chemical and physical inducers of the heat shock response (HSR). In this study we show that heat stress inhibits constitutive NF-kappaB DNA-binding activity in different types of B-cell malignancies, including multiple myeloma, activated B-cell-like (ABC) type of diffuse large B-cell lymphoma (DLBCL) and Burkitt's lymphoma presenting aberrant NF-kappaB regulation. Heat-induced NF-kappaB inhibition leads to rapid downregulation of the anti-apoptotic protein cellular inhibitor-of-apoptosis protein 2 (cIAP-2), followed by activation of caspase-3 and cleavage of the caspase-3 substrate poly(adenosine diphosphate ribose)polymerase (PARP), causing massive apoptosis under conditions that do not affect viability in cells not presenting NF-kappaB aberrations. NF-kappaB inhibition by the proteasome inhibitor bortezomib and by short-hairpin RNA (shRNA) interference results in increased sensitivity of HS-Sultan B-cell lymphoma to hyperthermic stress. Altogether, the results indicate that aggressive B-cell malignancies presenting constitutive NF-kappaB activity are sensitive to heat-induced apoptosis, and suggest that aberrant NF-kappaB regulation may be a marker of heat stress sensitivity in cancer cells.

Diffuse large B‐cell lymphoma presenting as piriformis syndrome

Piriformis syndrome (PS) is a rare condition characterized by pain and paresthesia of the buttock, often radiating to the posterior thigh. A patient with sciatica that was clinically suspicious for PS, underwent diagnostic work-up. A diagnosis of diffuse large B-cell lymphoma with neurolymphomatosis (NL) was made. To our knowledge, this is the first report of NL presenting as PS. NL is a possible cause of secondary PS.