Primary gastrointestinal non-Hodgkin lymphoma (PGI NHL) is one of the most common types of extranodal lymphoma, accounting for ~30–50% of all extranodal lymphomas. The aim of the present study was to investigate the clinical characteristics, diagnosis, treatment and prognosis of patients with PGI NHL. A total of 46 patients with PGI NHL (mean age, 50 years) were enrolled in this study, with a male:female ratio of 1.3:1. The most common site of PGI NHL was the stomach (52.2%), followed by the colon (34.8%) and small intestine (8.7%). The most common symptoms of PGI NHL included abdominal pain or discomfort (91.3%), loss of appetite (65.2%) and weight loss (56.5%) and the most common pathological subtype of PGI NHL was diffuse large B-cell lymphoma (DLBCL) (78.3%). Lesions were identified in 95.7% of PGI NHL patients under preoperative endoscopic examination, whereas the diagnosis rate was only 21.7% during preoperative endoscopic biopsy. All 46 patients underwent surgical treatment and 36 also received postoperative chemotherapy or radiotherapy. The follow-up time was 6–70 months in 37 PGI NHL patients, with 1-, 3- and 5-year survival rates of 81.1, 62.16 and 50.0%, respectively. The 5-year survival rate differed significantly according to clinical stage (P=0.002) and tumor size (P=0.0017) among patients with PGI NHL. However, there was no statistically significant difference in the 5-year survival rate between patients who received surgery alone and those who received surgery plus postoperative chemotherapy or radiotherapy (P=0.1371). Furthermore, there were no statistically significant differences in gender (P=0.127), clinical stage (P=0.828), histological subtype (P=1.000) and surgical modality (P=0.509) between patients with primary gastric non-Hodgkin lymphoma (PG NHL) and those with primary intestinal non-Hodgkin lymphoma (PI NHL). In conclusion, PGI NHLs are a heterogeneous group of diseases, whereas clinical stage and tumor size were identified as adverse prognostic factors of PGI NHL. Further studies, including a larger number of patients treated with surgery alone, are required in order to elucidate the precise role of surgery combined with postoperative chemotherapy or radiotherapy in the prognosis of PGI NHL.
non-Hodgkin lymphoma; gastrointestinal lymphoma; diagnosis; therapy; prognosis
Aims—To investigate the clinicopathological differences among gastric low grade MALT lymphomas (low MALT), large B cell lymphomas with low grade components (secondary high grade MALT lymphomas, high MALT), and diffuse large B cell lymphomas without low grade features (primary high grade MALT lymphomas, DLL).
Methods—Clinicopathological and morphological characters of 126 gastric lymphoma cases were studied: 82 cases of low MALT lymphoma including 40 that were surgically resected, 17 cases of high MALT lymphoma including 13 surgically resected, and 27 cases of DLL including 12 surgically resected.
Results—Age ranges were as follows: low MALT lymphoma, 34 to 85 years (mean 59.9); high MALT lymphoma, 53 to 88 years (mean 68.5); DLL, 29 to 83 years (mean 62.3). The average age for low and high MALT lymphomas was significantly different (p < 0.05), but there were no differences in other comparisons. There was a female predominance of low MALT lymphoma patients (female to male ratio, 47/35), while for high MALT patients the ratio was almost even (8/9), and for DLL patients there was a male predominance (11/16). Examination of surgically resected material showed that MALT lymphomas had a wider distribution in the gastric wall than DLL.
Conclusions—The findings suggest that at least some of the high grade gastric lymphomas, especially in patients younger than the fifth decade, do not originate from high grade transformation of low MALT lymphomas. It seems to take about one decade at least for high grade transformation of low MALT lymphomas.
Key Words: MALT lymphoma • stomach • transformation
Aim—To report the clinical and histological features and outcome of primary and secondary malignant lymphomas of the urinary bladder.
Methods—Eleven cases of malignant lymphoma of the urinary bladder were obtained from the registry of cases at St Bartholomews and the Royal London Hospitals. The lymphomas were classified on the basis of their morphology and immunophenotype, and the clinical records were reviewed.
Results—There were six primary lymphomas: three extranodal marginal zone lymphomas of mucosa associated lymphoid tissue (MALT) type and three diffuse large B cell lymphomas. Of the five secondary cases, four were diffuse large B cell lymphomas, one secondary to a systemic follicular follicle centre lymphoma, and one nodular sclerosis Hodgkins disease. Four patients with secondary lymphoma for whom follow up was available had died of disease within 13 months of diagnosis. Primary lymphomas followed a more indolent course. In one case, there was evidence of transformation from low grade MALT-type to diffuse large B cell lymphoma. The most common presenting symptom was haematuria. Cystoscopic appearances were of solid, sometimes necrotic tumours resembling transitional cell carcinoma, and in one case the tumours were multiple. These cases represented 0.2% of all bladder neoplasms.
Conclusions—Diffuse large B cell lymphoma and MALT-type lymphoma are the most common primary malignant lymphomas of the bladder. Lymphoepithelial lesions in MALT-type lymphoma involve transitional epithelium, and their presence in high grade lymphoma suggests a primary origin owing to transformation of low grade MALT-type lymphoma. Primary and secondary diffuse large B cell lymphomas of the bladder are histologically similar, but the prognosis of the former is favourable.
Key Words: bladder • lymphoma • mucosa associated lymphoid tissue lymphoma
Extranodal lymphoma may arise anywhere outside lymph nodes mostly in the gastrointestinal (GI) tract as non-Hodgkin's disease. We reviewed the clinicopathological features and treatment results of patients with primary GI lymphoma.
Materials and Methods:
A total number of 30 cases with primary GI lymphoma were included in this study. Patients referred to the Radiation Oncology Department of Omid Hospital (Mashhad, Iran) during a 5-year period (2006-11). Clinical, paraclinical, and radiological data was collected from medical records of the patients.
Out of the 30 patients with primary GI lymphoma in the study, 12 were female (40%) and 18 were male (60%) (male to female ratio: 3/2). B symptoms were present in 27 patients (90%). Antidiuretic hormone (LDH) levels were elevated in 9 patients (32.1%). The most common primary site was stomach in 14 cases (46.7%). Other common sites included small intestine and colon each in 8 patients (26.7%). All patients had histopathologically proven non-Hodgkin's lymphoma. The most common histologic subtype was diffuse large B-cell lymphoma (DLBL) in 16 patients (53.3%). In addition, 28 patients (93.3%) received chemotherapy with cyclophosphamide, vincristine, doxorubicin, prednisolone (CHOP regimen). The median course of chemotherapy was 6 cources. Moreover, 8 patients (26.7%) received radiotherapy with cobalt 60. The median follow-up time was 26 months. The overall 5-year survival rate was 53% and the median survival time was 60 months.
Primary GI lymphoma is commonly seen in stomach and small intestine and mostly is DLBCL or mucosa-associated lymphoid tissue (MALT) lymphoma.
Primary Gastrointestinal Lymphoma; Diffuse Large B-Cell Lymphoma; Extranodal Lymphoma
Primary gastrointestinal T-cell lymphoma is an uncommon entity and primary colon T-cell lymphoma is even rarer. The majority of enteropathy-associated T-cell lymphomas present predominantly as ulcers or strictures in the endoscopic examinations, while primary B-cell lymphomas commonly present as exophytic lesions. Ulcerative colon T-cell lymphoma may mimic Crohn's disease (CD), which is a chronic inflammatory disease of the intestines with ulcer and fistula formations difficult for clinicians to diagnose based on endoscopic observations alone. Like CD, T-cell lymphoma may be characterized by the presence of multiple skipped ulcers distributed from the terminal ileum to the descending colon. Furthermore, it is difficult to diagnose this unusual lymphoma by a single endoscopic biopsy. Typically, the histological composition of T-cell lymphoma is made of medium to large atypical cells located in the base of the ulcer with extension to the muscle layer and the adjacent mucosa. However, it is common that biopsy specimens show only mixed inflammatory changes where the lymphoma cells are hard to be identified. The differential diagnosis of malignant lymphoma must be considered when clinically diagnosed CD is refractory to the medical treatment or when its clinical behavior becomes aggressive. The current study presents a rare case of primary colon T-cell lymphoma in a 56-year-old male with marked recent weight loss, watery diarrhea and bilateral neck lymphadenopathy, who received a laboratory checkup and endoscopic workup for colon biopsy. The initial pathological report was consistent with mucosal inflammation and benign colon ulcers. Interestingly, the blood test showed a prominent eosinophilia. A biopsy of the enlarged neck lymph nodes done approximately 1 month after the colon biopsy unexpectedly showed T-cell lymphoma, which led to a review of the initial colonic biopsy specimens. Additional immunohistochemical stains were used accordingly, which showed positive results for CD3, CD45RO and LCA antibodies confirming the diagnosis of lymphoma. The endoscopic diagnosis of ulcerative colon T-cell lymphoma is frequently confused with inflammatory conditions of the large bowel such as CD, and tuberculosis colitis. Our study aims to emphasize the difficulty in differentiating this ulcerative form of colon T-cell lymphoma from the inflammatory bowel diseases and the importance of its differential diagnosis due to the much more aggressive clinical behavior of the T-cell lymphoma.
T-cell lymphoma; Colitis; Eosinophilia; Crohn's disease
Introduction: The distribution of the major subtypes of non-Hodgkin’s lymphoma (NHL) differs across geographic regions. This study, from the north Indian state of Punjab, has incorporated immunophenotypic findings while investigating the distribution of NHL subtypes based on World Health Organization (WHO)/ Revised European-American Classification of Lymphoid Neoplasms (REAL) system of classification.
Patients and methods: Over all seventy seven cases of lymphoma over a period of one year (between April 2012 and April 2013) were diagnosed in the Department of Pathology, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar (Punjab). Of these 30 cases (39%) were of Hodgkin’s Lymphoma (HL) and 47 cases (61%) were of Non Hodgkins lymphoma NHL.
Of the total of cases of lympho-proliferative disorders, the diagnosis of NHL was done by light microscopy alone. All the cases diagnosed provisionally as NHL were taken up for immunophenotyping with Immunohistochemical (IHC) studies. There was 100 % concordance between the light microscopy and IHC studies.
The individual NHL cases were classified according to the WHO/REAL classification according to the positive or relevant negative immonophenotypic expression and tabulated to ascertain the morphological spectrum of NHL in this part of the country.
Results: B-cell lymphomas formed 89.3%, whereas T-cell lymphomas formed 10.7% of the NHLs. Diffuse Large B-Cell Lymphoma (DLBCL) was the most common subtype (46.8% of all NHLs). B-cell small lymphocytic lymphoma, Mantle-Cell Lymphoma (MCL), marginal zone B-cell lymphomas (including MALT lymphomas), Diffuse, mixed small cleaved cell and large-cell type and Follicular centre-cell lymphomas amounted to 17%, 12.8%, 2.1%, 2.1% and 4.3%, respectively. Among the T-cell lymphomas, T-cell lymphoblastic lymphoma, anaplastic large-cell lymphomas of T/null-cell type, and Angioimmunoblastic T-cell lymphoma (AITL) accounted for 6.4%, 2.1%, and 2.1% of all NHL cases, respectively.
Conclusions: The distribution of NHL subtypes in India shows disparity with those from the rest of the world. Follicular Lymphoma (FL) and MCL are less common in India compared to Europe and the USA. Peripheral T-cell lymphomas and T/NK-cell lymphomas of nasal and nasal types, which are common in many other Asian countries, are also less prevalent. T-cell lymphoblastic lymphoma and anaplastic large T/null cell lymphoma are more prevalent in India.
Non Hodgkins lymphoma; WHO/REAL classification; Immunophenotyping; B-cell lymphomas; T-cell lymphomas
The Primary Breast Lymphomas (PBL) represent 0,38-0,70% of all non-Hodgkin lymphomas (NHL), 1,7-2,2% of all extranodal NHL and only 0,04-0,5% of all breast cancer. Most frequent PBLs are the diffuse large B cell lymphomas; in any case-reports MALT lymphomas lack or are a rare occurrence. Their incidence is growing. From 1880 (first breast resection for "lymphadenoid sarcoma" carried out by Gross) to the recent past the gold standard treatment for such diseases was surgery. At present such role has lost some of its importance, and it is matter of debate.
Twenty-three women affected by PBL underwent surgery. Average age was 63 years (range: 39-83). Seven suffered of hypothyroidism secondary to autoimmune thyroiditis. Fourteen patients underwent mastectomy, nine patients received quadrantectomy (average neoplasm diameter: 1,85 cm, range: 1,1-2,6 cm). In 10 cases axillary dissection was carried out. Pathologic examination revealed 16 diffuse large B cell lymphomas and 7 MALT lymphomas.
Seven patients in the mastectomy group had a recurrence (50%), and all of them with diffuse large B cell lymphomas at stage II. Two of these had not received chemotherapy. No patient undergoing quadrantectomy had recurrence. In the mastectomy group disease free survival (DFS) at 5 and 10 years was 57 and 50%. Overall survival (OS) at 5 and 10 years was 71.4% and 57.1% respectively. All recurrences were systemic. DFS and OS at 5 and 10 years was 100% in the quadrantectomy group. In the patients with recurrence mortality was 85.7%. For stage IE DFS and OS at 5 and 10 years were 100%. For stage II DFS at 10 years was 62.5% and 56.2% respectively; OS at 5 and 10 years was 75% and 62.5% respectively. For MALT lymphomas DFS and OS at 5 and 10 years were 100%. For diffuse large B cell lymphomas DFS at 5 and 10 years was 62.5% and 56.2% respectively; OS at 5 and 10 years was 75% and 62,5% respectively.
The role of surgery in this disease should be limited to get a definitive diagnosis while for the staging and the treatment CT scan and chemio/radioterapy are repectively mandatory. MALT PBLs have a definitely better prognosis compared to large B cell lymphomas. The surgical treatment must always be oncologically radical (R0); mastectomy must not be carried out as a rule, but only when tissue sparing procedures are not feasible. Axillary dissection must always be performed for staging purposes, so avoiding the risk of under-staging II o IE, due to the possibility of clinically silent axillary node involvement.
Diffuse large B-cell lymphoma (DLBCL) constitutes most primary central nervous system (CNS) lymphoma (PCNSL), whereas T-cell, low-grade and Burkitt’s lymphomas (BL) are rarely encountered. Due to the paucity of cases, little is known about the clinical features and treatment outcomes of PCNSL other than DLBCL. The objective of this study was to describe the clinical characteristics and outcomes for patients with PCNSL other than DLBCL. Fifteen patients, newly diagnosed with PCNSLs other than DLBCL between 2000 and 2010, were included. The male to female ratio was 0.67:1 with a median age of diagnosis of 31 years (range 18–59). Pathologic distributions were as follows: peripheral T-cell lymphoma (PTCL; n = 7), marginal zone B-cell lymphoma (MZBCL; n = 1), lymphoplasmacytic lymphoma (LPL; n = 2), Burkitt’s lymphoma (n = 1), other unspecified (T-cell lineage, n = 2; B-cell lineage, n = 2). Thirteen patients (87%) showed Eastern Cooperative Oncology Group performance score (ECOG PS) 1–2. The remaining two were one PTCL patient and one Burkitt’s lymphoma patient. Of the nine patients with T-cell lymphoma, five (56%) had multifocal lesions, and one (20%) with LPL of the five patients with B-cell lymphoma showed a single lesion. Leptomeningeal lymphomatosis was identified in two patients (one with Burkitt’s lymphoma and one with unspecified B-cell lymphoma). Two patients (22%) with T-cell lymphoma died 7.7 and 23.3 months later, respectively, due to disease progression, despite HD-MTX-based therapy. Six patients with T-cell lymphoma (6/9, 66.7%) and four patients with low-grade B-cell lymphoma (4/5, 80%) achieved complete response and have survived without relapse (Table 3). One patient with Burkitt’s lymphoma showed poor clinical features with ECOG PS 3, deep structure, multifocal, and leptomeningeal lymphomatosis, and died 7.6 months after the initiation of treatment. In comparison with previously reported DLBCLs (median OS 6.4 years, 95% CI 3.7–9.1 years), T-cell lymphoma showed equivocal or favorable clinical outcomes and low-grade B-cell lymphomas, such as MZBCL and LPL, had a good prognosis. However, primary CNS Burkitt’s lymphoma presented poor clinical outcomes and showed a comparatively aggressive clinical course. In conclusion, primary CNS lymphoma other than DLBCL occurred more in younger patients and showed a generally good prognosis, except for Burkitt’s lymphoma. Further research on treatment strategies for Burkitt’s lymphoma is needed.
Primary CNS lymphoma; Diffuse large B-cell lymphoma
To study the pattern of ocular adnexal lymphoproliferative disorders (OALD) in an ophthalmic referral center in Saudi Arabia and to review their, histopathological characteristics with clinical correlation.
Retrospective chart review of 40 cases of patients who underwent incisional biopsy with the suspected diagnosis of periocular and/or adnexal lymphoid lesions over the period: 2000–2012 at the King Khaled Eye Specialist Hospital (KKESH), Riyadh, Saudi Arabia. The routine histopathologic slides are reviewed by a single pathologist to identify cases of Benign Reactive Lymphoid Hyperplasia (RLH), Atypical Lymphoid Hyperplasia and probable lymphoma. The identification of the specific types of lymphoma is performed at a tertiary general hospital: King Faisal Specialist Hospital and Research Centre (KFSH&RC).
Forty patients are included with an age range of 11–91 years and a median of 36 years. The males constitute 70% and females 30% of the cases. The right eye and/or orbit are involved in 48%. The left eye is involved in 45% while a bilateral disease is found in 7.5%. The median duration of symptoms is 5 months. The site distribution is conjunctiva (42.5%), orbit (25%), lacrimal gland (12.5%), eyelid (10%), lacrimal sac (7.5%) and caruncle (2.5%). One case is excluded after histopathologic diagnosis of malignant melanoma. Diagnosis in the remaining 39 cases includes: RLH in 14 cases (35%), atypical lymphoid hyperplasia in three cases (9%), and lymphoma in 22 cases (56%). Classification of the lymphoma group is: extranodal marginal zone lymphoma (EMZL) in 9/22 cases (41%), diffuse large B cell lymphoma (DLBCL) in 4/22 cases (18%), Castelman’s disease in 3/22 cases (14%), Burkitt’s lymphoma in 2/22 cases (9%), follicular lymphoma and T cell-rich B cell lymphoma: one case each (4.5%).Two cases remain unclassified.
We have a wide age range which is comparable to other studies. Our results show male predominance and the commonest site of involvement is conjunctival, however if RLH cases are excluded, the commonest site for lymphoma is orbit/lacrimal gland in 45% followed by conjunctival in 23%. The commonest type of lymphoma is: EMZL in 41% followed by DLBCL in 18% then other types of lymphoma including follicular lymphoma.
Lymphoma; Orbit; Adnexal; Lymphoid hyperplasia; Lacrimal
Primary gastrointestinal lymphoma comprises 10-15% of all non-Hodgkin lymphomas and encompasses 30-40% of the total extranodal lymphomas. Approximately 60-75% of cases occur in the stomach, and then the small bowel, ileum, cecum, colon and rectum. Lymphoid neoplasms may consist of mature B, T and less commonly extranodal NK/T cells. Of these, the two most frequently encountered histologic subtypes are extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), where Helicobacter pylori infection is implicated in a number of cases, and diffuse large B cell lymphoma. Several B cell lymphomas are associated with chromosomal aberrations. Enteropathy-associated T cell lymphoma, type I in particular, usually arises in a background of celiac disease. T cell gene rearrangement confirms clonality. NK/T cell neoplasms are invariably associated with Epstein-Barr virus infection and are often aggressive; thus, differentiation from a benign NK-cell enteropathy is paramount. Although incidence of other hematopoietic malignancies in the gastrointestinal tract such as plasma cell myeloma associated with amyloidosis, plasmablastic lymphoma, Hodgkin disease, histiocytic sarcoma and mast cell sarcoma is extremely rare, these entities have been documented, with the latter two demonstrating aggressive clinical behavior. Endoscopic ultrasonography is an important adjunct in disease staging and follow-up. Conservative antibiotic treatment of stage I MALT lymphomas with associated Helicobacter pylori infection achieves good clinical outcome with high remission rate. Chemotherapy, radiation and rarely surgery are reserved for advanced diseases or cases resistant to conservative therapy and those not associated with Helicobacter pylori infection.
Gastrointestinal lymphomas; MALT lymphoma; NK/T-cell enteropathy
The gastrointestinal (GI) tract is the most common extranodal site of involvement in non-Hodgkin lymphoma (NHL). Primary GI NHL is frequently discussed in survival analyses. Primary intestinal NHL is significantly different from primary gastric NHL with regard to its clinical features, pathological subtype, treatment and prognosis. The small intestine is involved in lymphoma less often than the large intestine. The present study aimed to analyze the clinical and pathological characteristics of primary NHL of the small intestine and its prognostic factors. A retrospective analysis was performed on clinical data from 313 cases of NHL that occurred between 1995 and 2008 in the Tri-Service General Hospital (National Defense Medical Center, Taipei, Taiwan). Among these cases, 11 cases of primary NHL of the small intestine were identified. A Cox model was used to perform the multivariate analysis. The Kaplan-Meier method was used for the survival analysis. From the 11 patients with primary NHL of the small intestine, seven patients were male (63.6%) and four patients were female (36.3%). Furthermore, nine patients (81.8%) were diagnosed with B-cell lymphoma, of which five (45.5%) were also diagnosed with diffuse large B-cell lymphoma (DLBL). Abdominal pain and/or distention were present in six (54.5%) of the patients and jejunum involvement was also observed in six (54.5%) of the 11 patients. The mean overall survival (OS) time of the 11 patients was 27.2 months and the four-year survival rate was 36.3%. The mean OS time in the patients with jejunum involvement was shorter than in those without jejunum involvement (16.9 vs. 39.6 months), although this difference was not significant (P=0.657). Surgical treatment was performed on four of the six patients with jejunum involvement due to an acute abdomen or perforation-related peritonitis. The results of the present study indicate that DLBL is the most common subtype of primary lymphoma of the small intestine, and that the site involved in NHL may affect the potential for surgery in patients with intestinal lymphoma. Furthermore, patients with primary lymphoma of the small intestine have been found to have a poor outcome compared with those with lymphoma in other regions of the GI tract. In the present study, a similar trend was observed, however, the sizes of the subgroups of primary lymphoma of the small intestine were too small for individual analysis.
intestine; non-Hodgkin lymphoma; Taiwan
Mucosa-associated lymphoid tissue (MALT) lymphomas are extranodal lymphomas that arise from B lymphocytes located in the marginal zone of lymphoid follicles. Although, there is a substantial amount of lymphoid tissue in the gastrointestinal tract, MALT lymphomas usually arise in chronically inflamed sites that are normally devoid of lymphoid tissue. The best example is gastric MALT lymphoma that is almost always associated with Helicobacter pylori. Primary pancreatic lymphoma (PPL) is an extremely rare tumor (1% incidence) and is often confused with pancreatic adenocarcinoma. By suspecting PPL on clinical and imaging grounds, surgery and its associated complications can be avoided, since the mainstay of the treatment is non-surgical strategies including chemotherapy. We represent a case of a 45-year-old male presented with abdominal pain and vomiting. Upper endoscopy showed multiple gastric ulcers, biopsies revealed non-specific inflammatory ulcers. The patient was given 4-weeks course of proton pump inhibitor with no improvement. After few months, he complained of severe abdominal pain relieved by leaning forward and associated with repeated vomiting. Upper endoscopy revealed multiple umbilicated gastric masses, 10-20 mm in diameter. Biopsies were taken, histopathology and immunohistochemistry revealed MALT lymphoma. Endoscopic ultrasonography was done to the patient and it showed a pancreatic head mass, fine-needle aspiration was done, histopathology and immunohistochemistry revealed PPL. The patient received chemotherapy for MALT lymphoma with near total relief of symptoms and disappearance of gastric and pancreatic masses.
This is a rare case having MALT lymphoma associated with PPL.
Primary lymphoma of the urinary bladder is exceedingly rare, representing 0.2% of all extranodal non-Hodgkin's lymphoma. Although Matsuno et al. and others state the most common type is mucosa-associated lymphoid tissue (MALT) lymphoma, 20% of all the primary lymphomas of the urinary bladder are considered to be high grade neoplasms; the majority being diffuse large B-cell lymphoma (DLBCL). This is a case report of a 48-year-old man that presented with hematuria, frequency, nocturia, and flank pain that was found to have high grade DLBCL. Twenty-six other cases of both low and high grade primary bladder lymphomas were selected in order to provide a thorough comparison of different treatment modalities. Of the cases reviewed, bladder lymphoma was more common in females (2:1). The average age at diagnosis was 63.9 years old (low grade: 68.7 years old, high grade: 58.8 years old). The most common low-grade neoplasm was MALT lymphoma (85.7%). For the low-grade malignancies, the most successful treatments were simple therapies (2 transurethral resection of a bladder tumour [TURBT], 1 antibiotics), solitary chemotherapy, and combination TURBT/chemo; all 3 of which achieved 100% clinical remission (CR) in the cases reviewed. The most common high grade neoplasm was DLBCL (76.9%). The most successful therapies used to treat high grade lesions were solitary chemotherapy (cyclophosphamide, duanorubacin, vincristine, prednisolone [CHOP] or ritoximab, CHOP [R-CHOP]) and combination therapies (2 radiation/CHOP, 2 surgery/CHOP). In the agreement with the current literature, this review has shown that simple therapies (TURBT) are equally as effective as aggressive treatments (chemotherapy, radiation) and should therefore be used as first line treatment in low grade tumors. For high grade malignancies, chemotherapy (R-CHOP or CHOP) alone or combination therapy (CHOP/surgery or CHOP/radiation) is recommended.
Cyclophosphamide; duanorubacin; vincristine; prednisolone chemotherapy; diffuse large B-cell lymphoma; extranodal non-Hodgkin's lymphoma; hematuria; primary bladder lymphoma
To define the clinical and histopathological characteristics of primary lacrimal sac lymphoma in a predominantly white population.
Specimens of lacrimal sac lymphoma and follow up data were solicited from members of the Ophthalmic Oncology Task Force of the European Organization for Research and Treatment of Cancer (EORTC) and the European Ophthalmic Pathology Society (EOPS). Specimens were stained with haematoxylin and eosin and an immunohistochemical panel against leucocyte antigens was applied. Diagnosis was reached by consensus of five experienced pathologists according to the World Health Organization classification system. The histopathological findings were correlated with the clinical data.
Of 15 primary lacrimal sac lymphomas, five (33%) were diffuse large B cell lymphoma (DLBCL), five (33%) were extranodal marginal zone B cell lymphoma of mucosa associated lymphoid tissue (MALT lymphoma), three were classified as “transitional MALT lymphoma,” being in transition from MALT lymphoma to DLBCL, and two were unclassified B cell lymphomas. Nine of the patients were female, and the median age at the time of diagnosis was 71 years (range 45–95 years). The most frequent presenting symptoms were epiphora (85%), swelling in the region of the lacrimal sac (79%), and dacryocystitis (21%). All but one patient presented in stage I. Systemic spread occurred in three of nine patients (33%). The 5 year overall survival was 65%.
DLBCL and MALT lymphoma are equally common in the lacrimal sac in contrast with the remaining periorbital and/or orbital region where MALT lymphoma predominates.
ocular lymphoma; lacrimal sac; MALT lymphoma
The gastrointestinal tract is the most common location for primary extranodal non-Hodgkin lymphoma (NHL) with cases less commonly found in the intestine. The majority of primary intestinal B-cell lymphomas are exophytic, whereas enteropathy-associated T-cell lymphomas present predominantly as thickened plaques, ulcers or strictures. Crohn’s disease (CD) is a chronic inflammatory disease of the intestines with fissures and ulcers, which is difficult for clinicians to diagnose based on endoscopic observations alone. Malignant lymphoma must be considered when clinically diagnosed CD is refractory to medication or when its clinical course becomes aggressive. The current study presents a rare case of primary colon T-cell lymphoma in a 16-year-old male with poor prognosis, as well as a case of gastrointestinal lymphoma occurring in the duodenum and colon in a 62-year-old male with a 10-year history of NHL. It was difficult to determine the diagnosis by a single endoscopic biopsy as the majority of biopsy specimens revealed mixed inflammation within which the lymphoma cells were difficult to identify. The present study indicated that it is important to recognize ulcerative or stenotic lymphoma and to differentiate it from CD as it exhibits a much more aggressive clinical behavior. The correct diagnosis may be confirmed by careful histopathological study and ancillary examination.
lymphoma; Crohn’s disease; enteropathy; endoscopy
Primary non-Hodgkin’s lymphoma (NHL) of the breast constitutes 0.04%-0.53% of all malignancies and 2.2% of extra nodal lymphomas. In total, 7%-8% of all B-cell lymphomas are the mucosa-associated lymphoid tissue (MALT) type, of which up to 50% of primary gastric MALT lymphoma. Herein we present a patient with breast MALT lymphoma that transformed to diffuse large B-cell lymphoma (DLBCL). A 69-year-old female presented with a mass on her left breast. Physical examination showed a 3×3-cm mass located 1 cm from the areola on the upper lateral quadrant of the breast at the 1 o’clock position, which was fixed and firm. Excisional biopsy was performed and pathologic examination of the specimen showed MALT lymphoma transformation to DLBCL. The patient was staged as II-EA. The rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) protocol was scheduled as treatment. Following 6 courses of R-CHOP, 2 additional courses of rituximab were administered. Positron emission tomography (PET)-CT was done at the end of the treatment. PET showed that the patient was in complete remission. At the time this report was written, the patient was being followed-up at the outpatient clinic on a regular basis. Lymphoma of the breast is a rarity among malignant tumors of the breast. The most common type of lymphoma is DLBCL. Breast MALT lymphoma is extremely rare. Primary MALT lymphoma of the breast can transform from low grade to high grade and recurrence is possible; therefore, such patients should be monitored carefully for transformation.
Primary breast mucosa-associated lymphoid tissue (MALT) lymphoma; Diffuse large B-cell lymphoma
Primary adrenal lymphoma (PAL) is an extremely rare subtype of extranodal non-Hodgkin’s lymphoma. Some researchers have reported some of the characteristics of PAL and its association with poor prognosis; however, the clinicopathological features of PAL remain to be elucidated.
From 2008 to 2011 we experienced seven cases of PAL in our institutions. We retrospectively analyzed the clinical and pathological features of these patients.
The patients ranged in age from 50 to 85 years, with a median of 71 years. The overall male:female ratio was 6:1. All seven patients were diagnosed with diffuse large B-cell lymphoma (DLBCL) pathologically. Bilateral adrenal involvement was confirmed in five patients. The median largest tumor diameter at diagnosis was 58 mm. The Ki-67 index was generally high (>70%). All patients were treated with rituximab-containing chemotherapy, and central nervous system (CNS) prophylaxis was conducted for three patients. One patient with CNS involvement at the time of the diagnosis also received whole-brain radiation. The overall survival rate at two years was 57% (median follow-up; 24.8 months). It is noteworthy that the three patients who received a full course of the rituximab-containing regimen and CNS prophylaxis are currently alive without disease relapse, and that none of the seven patients died due to progression of lymphoma.
Primary adrenal DLBCL can be a clinically aggressive disease entity. Rituximab-containing chemotherapy combined with CNS prophylaxis could be a reasonable option for the treatment of PAL; however, analyses of more PAL cases are needed for the establishment of this strategy.
Primary adrenal lymphoma; Diffuse large B-cell lymphoma; Adrenal insufficiency; Central nervous system infiltration; Rituximab
AIM—To classify ocular adnexal lymphomas according to the Revised European and American Lymphoma (REAL) classification and to determine any correlation between clinical features or histomorphological variables with the patients' outcome.
METHODS—Conventional and immunohistology were performed on representative sections of 53 specimens of 46 patients with ocular adnexal lymphoma. The antibodies used were CD20, BCL-2, CD21, CD23, CD43, CD3, CD5, p53, cyclin D1, pan-cytokeratin, kappa, lambda, IgD, and IgM. The growth fraction of the tumours was determined using the MIB-1 antibody directed against the Ki-67 antigen. Clinical follow up data regarding the outcome were obtained from the treating physicians and/or hospital files. The Student's t test and log rank test were used for statistical analysis.
RESULTS—The patient collective consisted of 29 females and 17 males with an age range of 32-89.7 years (average 63 years). Almost all specimens represented B cell non-Hodgkin's lymphomas: extranodal marginal zone lymphoma (EMZL) (n=38), diffuse large cell B cell lymphoma (n=8), lymphoplasmocytic lymphoma/immunocytoma (n=2), mantle cell lymphoma (n=2), follicle centre lymphoma (n=1), and plasmacytoma (n=1). One case of a secondary anaplastic large cell lymphoma of T cell type (T-ALCL) was diagnosed. The majority of the patients had stage I disease. A variety of therapeutic regimens was administered, the main form of treatment being radiotherapy. The average follow up time was 85 months. Complete remission was achieved in 24 patients (10 after excision alone, eight after radiotherapy alone, three after combined excision and radiotherapy, one after chemotherapy alone, and two after combined radiotherapy and chemotherapy). 12 patients died of causes related to lymphoma; in one patient the cause of death was unknown. Six patients had persistent tumour at final follow up and two patients were lost to follow up. The stage at presentation, as well as the lymphoma malignancy category, had a significant correlation with the final course of the disease (p=0.0001 and p=0.03, respectively). A significant correlation was also noted between the final outcome (p<0.05) and tumour cell expression for Ki-67 antigen and p53 protein.
CONCLUSION—67% of patients with ocular adnexal lymphoma had EMZL. The stage at presentation had a significant influence on the final outcome. MIB-1 and p53 expression by the tumour cells proved to be important immunohistochemical markers concerning the prognosis. It is suggested that, following thorough staging investigations, primary EMZL (stage I) (if accessible) should be treated with excisional biopsy and subsequent low dose radiotherapy. Primary diffuse large cell B cell lymphoma of the ocular adnexa requires at least similar therapeutic measures and regular intensive follow up.
To identify occupations suspected to be associated with malignant lymphoma and to generate new hypotheses about occupational risks in a multicentre, population based case control study.
Male and female patients with malignant lymphoma (n = 710) aged 18–80 years of age were prospectively recruited in six study regions in Germany. For each newly recruited lymphoma case, a sex, region, and age matched control was drawn from the population registers. Odds ratios and 95% confidence intervals for major occupations and industries were calculated using conditional logistic regression analysis, adjusted for smoking (in pack‐years) and alcohol consumption. Patients with specific lymphoma subentities were additionally compared with the entire control group using unconditional logistic regression analysis.
The following economic/industrial sectors were positively associated with lymphoma: food products, beverages, tobacco; paper products, publishing and printing; and metals. Chemicals; real estate, renting, and business activities were negatively associated with lymphoma diagnosis. The authors observed an increased overall lymphoma risk among architects; maids; farmers; glass formers; and construction workers. Shoemaking and leather goods making was negatively associated with the lymphoma diagnosis (although based on small numbers). In the occupational group analysis of lymphoma subentities, Hodgkin's lymphoma was significantly associated only with rubber and plastic products making; diffuse large B cell lymphoma risk was considerably increased among metal processors; follicular lymphoma showed highly significant risk increases for several occupational groups (medical, dental, and veterinary workers; sales workers; machinery fitters; and electrical fitters); and multiple myeloma showed a particularly pronounced risk increase for farmers as well as for agriculture and animal husbandry workers.
The results partly confirm previously defined occupational risks. Occupational risk factors for follicular lymphomas might differ from the overall risk factors for malignant lymphoma.
malignant lymphoma; occupation; case control study
The gastric lesions of various lymphomas were observed at the cellular level using endocytoscopy.
Endocytoscopy and magnifying endoscopy with narrow band imaging (NBI) were performed in 17 patients with lymphomas of the stomach. The lesions consisted of 7 with low-grade mucosa-associated lymphoid tissue (MALT), 5 with gastric involvement by adult T-cell leukemia/lymphoma (ATLL), 4 with diffuse large B-cell lymphoma (DLBCL), and 1 with peripheral T-cell lymphoma.
On conventional endoscopy, 9 were classified as having superficial spreading type, 7 were mass-forming type, and 1 was diffuse infiltrating type. Anti-H. pylori treatment was given in the 7 MALT lymphoma cases. NBI magnification endoscopy invariably showed dilatation or ballooning and destruction of gastric pits and elongation and distortion in microvessels. Endocytoscopy showed mucosal aggregation of interstitial cellular elements in almost all gastric lymphoma cases. The nuclear diversity in size and configuration was exclusively seen in gastric lymphomas other than MALT lymphoma, whereas the nuclei of MALT lymphoma cells were regular and small to moderate in size. Inter-glandular infiltration by lymphomatous cell elements was frequently observed in MALT lymphoma and DLBCL, but it was uncommon in peripheral gastric T-cell malignancies. Endocytoscopy could identify the disease-specific histology, the lymphoepithelial origin, as inter-glandular infiltration of cellular components in MALT lymphoma and the possibly related DLBCL cases. Complete regression (CR) was observed in 2 of the 7 MALT lymphoma patients. In the 2 patients with CR who underwent repeat endocytoscopy, the ultra-high magnification abnormalities returned to normal, while they were unchanged in those without tumor regression.
On endocytoscopy, intra-glandular aggregation of cellular components was invariably identified in lymphomas of the stomach. Nuclear regularity in size and configuration may indicate the cytological grade, differentiating the indolent low-grade from aggressive lymphoproliferative diseases. The inter-glandular infiltration seen on endocytoscopy can indicate the lymphoepithelial lesions seen in MALT lymphoma and related DLBCL. Endocytoscopy would be applicable for virtual histopathological diagnosis of different lymphoproliferative disorders and their clinical assessment during ongoing endoscopy.
ATLL; DLBCL; Endocytoscopy; Gastric low-grade MALT lymphoma; H. pylori; Narrow band imaging
AIM: To investigate the feasibility of double-balloon endoscopy (DBE) to detect jejunoileal lymphoma, compared with fluorodeoxyglucose positron emission tomography (FDG-PET).
METHODS: Between March 2004 and January 2011, we histologically confirmed involvement of malignant lymphoma of the jejunoileum in 31 patients by DBE and biopsy. In 20 patients of them, we performed with FDG-PET. We retrospectively reviewed the records of these 20 patients. Their median age was 64 years (range 50-81). In the 20 patients, the pathological diagnosis of underlying non-Hodgkin’s lymphoma (NHL) comprised follicular lymphoma (FL, n = 12), diffuse large B cell lymphoma (DLBCL, n = 4), mantle cell lymphoma (MCL, n = 2), enteropathy associated T cell lymphoma (ETL, n = 1) and anaplastic large cell lymphoma (ALCL, n = 1).
RESULTS: Ten cases showed accumulation by FDG-PET (50%). FDG-PET was positive in 3 of 12 FL cases (25%) while in 7 of 8 non-FL cases (88%, P < 0.05). Intestinal FL showed a significantly lower rate of positive FDG-PET, in comparison with other types of lymphoma. Cases with endoscopically elevated lesions (n = 10) showed positive FDG-PET in 2 (20%), but those with other type NHL did in 8 of 10 (80%, P < 0.05). When the cases having elevated type was compared with those not having elevated type lesion, the number of cases that showed accumulation of FDG was significantly smaller in the former than in the latter.
CONCLUSION: In a significant proportion, small intestinal involvement cannot be pointed out by FDG-PET. Especially, FL is difficult to evaluate by FDG-PET but essentially requires DBE.
Double-balloon endoscopy; Non-Hodgkin’s lymphoma; Jejunoileum; Fluorodeoxyglucose positron emission tomography; Follicular lymphoma
BACKGROUND: Various histological classifications developed for nodal lymphomas failed to be of value in extranodal lymphomas. More recently, gastric lymphoma is considered to represent a distinctive group derived from mucosa associated lymphoid tissue (MALT). AIM: To study the prognostic value of malignancy grading based on the concept that most gastric lymphomas are of MALT origin, the endoscopic as well as clinical characteristics in 114 patients with primary gastric non-Hodgkin's lymphoma were evaluated. RESULTS: In univariate analysis, patients with low grade lymphoma (n = 51) were younger, had less advanced stage, and less frequently bulky disease than those with high grade lymphoma (n = 63). In multivariate analysis weight loss and increased erythrocyte sedimentation rate were significantly less frequent in low grade (45% and 22%) compared with high grade lymphoma (75% and 53%). In low grade lymphoma endoscopic findings were often interpreted as a benign condition (27 of 51), in contrast with high grade lymphoma, where carcinoma was most frequently (37 of 63) suspected. In low grade lymphoma complete remission rate was 92%, and five year survival 75%, In high grade lymphoma results were significantly less favourable (p = 0.0001): complete remission in 68%, and a five year survival of 46%. CONCLUSION: Malignancy grading was strongly correlated with treatment outcome; endoscopically low grade lymphoma was often hard to distinguish from benign conditions, whereas high grade lymphoma often revealed carcinoma-like features.
In a multicenter cohort, unmasking immune reconstitution inflammatory syndrome (IRIS) was observed in 12% of HIV-associated lymphomas. Presentation and survival for lymphoma IRIS were similar to non-IRIS, with possibly increased early mortality among IRIS cases.
Background. Lymphoma incidence is increased among human immunodeficiency virus (HIV)–infected individuals soon after antiretroviral therapy (ART), perhaps due to unmasking immune reconstitution inflammatory syndrome (IRIS). Clinical characteristics and survival for unmasking lymphoma IRIS have not been described.
Methods. We studied lymphoma patients in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) from 1996 until 2011. Unmasking lymphoma IRIS was defined as lymphoma within 6 months after ART accompanied by a ≥0.5 log10 copies/mL HIV RNA reduction. Differences in presentation and survival were examined between IRIS and non-IRIS cases.
Results. Of 482 lymphoma patients, 56 (12%) met criteria for unmasking lymphoma IRIS. Of these, 12 (21%) had Hodgkin lymphoma, 22 (39%) diffuse large B-cell lymphoma, 5 (9%) Burkitt lymphoma, 10 (18%) primary central nervous system lymphoma, and 7 (13%) other non-Hodgkin lymphoma. Median CD4 cell count at lymphoma diagnosis among IRIS cases was 173 cells/µL (interquartile range, 73–302), and 48% had suppressed HIV RNA <400 copies/mL. IRIS cases were similar overall to non-IRIS cases in histologic distribution and clinical characteristics, excepting more frequent hepatitis B and C (30% vs 19%, P = .05), and lower HIV RNA at lymphoma diagnosis resulting from the IRIS case definition. Overall survival at 5 years was similar between IRIS (49%; 95% confidence interval [CI], 37%–64%) and non-IRIS (44%; 95% CI, 39%–50%), although increased early mortality was suggested among IRIS cases.
Conclusions. In a large HIV-associated lymphoma cohort, 12% of patients met a uniformly applied unmasking lymphoma IRIS case definition. Detailed studies of lymphoma IRIS might identify immunologic mechanisms of lymphoma control.
HIV/AIDS; lymphoma; Hodgkin lymphoma; non-Hodgkin lymphoma; immune reconstitution inflammatory syndrome
Gastrointestinal lymphoma is the most common form of extranodal lymphoma, accounting for 30%–40% of cases. The most commonly involved site is the stomach (60%–75% of cases), followed by the small bowel, ileum, cecum, colon and rectum. The most common histological subtypes are diffuse large B-cell lymphoma (DLBCL) and marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT). Helicobacter pylori infection has been implicated in the pathogenesis of MALT gastric lymphoma, but its role in gastric diffuse large B-cell non-Hodgkin's lymphoma (NHL) is controversial. The therapeutic approach for patients with gastric NHL has been revised over the last 10 years. Conservative treatment with anthracycline-based chemotherapy alone or in combination with involved-field radiotherapy has replaced gastrectomy as standard therapy in cases with DLBCL. Additionally, MALT lymphomas are mainly treated with antibiotics alone, which can induce lasting remissions in those cases associated with H. pylori infection. Nevertheless, various therapeutic aspects for primary gastric lymphomas are still controversial and several questions remain unanswered. Among others, the role of rituximab, consolidation radiotherapy as well as H. pylori eradication in histological aggressive subtypes warrants better clarification.
diffuse large B-cell lymphomas; extranodal lymphomas; Helicobacter pylori infection; mucosa-associated lymphoid tissue; primary gastric lymphomas
The proper histopathological characterization of malignant lymphomas requires the use of immunohistochemistry along with other molecular pathology techniques.
Materials and Methods
Malignant lymphomas histologically diagnosed in our hospital were reclassified according to the WHO scheme using immunohistochemistry while in-situ hybridization was performed for the detection of Epstein-Barr virus encoded RNA.
There were 83 cases of lymphoma. The male to female ratio was 1.9:1 while the overall mean age was 41.7 years. Non-Hodgkin lymphomas (NHL) constituted about 79.5% of cases. The majority of cases (98.8%) were B-cell lymphomas. Nine subtypes of lymphomas were identified with diffuse large B-cell lymphomas (56.4% of which were of the germinal centre type) constituting the largest group (47.0%). Intermediate and high grade subtypes were more common. The majority of cases (72.3%) were nodal lymphomas with cervical lymph node being the commonest site (48.2%). Only classical Hodgkin lymphoma (HL) (20.5%) was seen of which the mixed cellularity subtype was the most common. Epstein Barr virus (EBV) encoded ribonucleic acid was detected in 7 cases (8.4%) including 4 cases of HL, 2 cases of Burkitt lymphoma and the only case of plasmablastic lymphoma. About five cases were reclassified as non-lymphoid malignant lesions.
Immunohistochemistry is vital to the proper classification of lymphomas even in a resource poor environment. Although nine subtypes of lymphomas were identified, diffuse large B-cell lymphomas formed the largest single group. Epstein-Barr virus probably plays an important role in lymphomatogenesis in this environment. A larger multicentre study is required to prove this.