AN EPIDEMIOLOGICAL, CLINICAL AND PATHOLOGICAL STUDY OF LYMPHOMAS OF THE BONE AND MUSCULOSKELETAL SYSTEM AMONG POPULATION FROM THE SOUTH OF IRAQ

Lymphomas of the bone and musculoskeletal tissue are uncommon. Yet, they constitute a certain frequency that they merit certain consideration. A study was conducted to clarify the behavior of such type of lymphomas in the South of Iraq, epidemiologically, clinically, pathologically, biochemically and immunologically. Results show that they form minority among total lymphoma cases, but they were the third common type among extranodal lymphomas with male gender, adult age and urban residency predominance. There was a predominance of low performance status, absence of B symptoms, neurological and musculo-skeletal manifestations, secondary bone, especially the spine, involvement. NonHodgkin lymphoma (NHL) was the most predominant, mainly the intermediate grade, with diffuse large cell lymphoma (DLCL) and Burkitt lymphoma (BL) as the main histological types encountered. Hematologically, there was mild anemia, rapid ESR (> 50 mm), normal platelets count in the majority, leucocytosis in < half and monocytopenia predominance. Biochemically they were characterized by normal liver function tests with the exception of high serum alkaline phosphatase, normal total serum proteins, hypoalbuminemia, normal serum urea, creatinine & uric acid, hypercalcemia, with serum LDH and B2MG elevation in the majority. Serum anti EB virus antibodies were seen in 1/4th of cases and the majority were of the higher IPI scores (both high intermediate & high). Those results were comparable to some and contradicting to other studies elsewhere. Introduction ymphomas constitute a heterogeneous group of clonal lymphoid system neoplasms arising as a result of a one or more of somatic mutations in a lymphocyte progenitor 1 ). They include distinct disorders defined by their clinical, histological, immunological, molecular, and genetic characteristics. Each one of these represents a clonal expansion of a normal precursor cell 2 . They rank as the 6th in incidence and mortality among malignancies at global level 3 . However, in Basra City, they occupied the 3rd rank among malignancies in males and the 2nd in females and represent 8.2% of all new malignant cases registered over the years 2005-2008 4 . Primary bone lymphomas (PBL), (defined as lymphoma localized to the bone without evidence of lymph nodes or other tissues at presentation: a modification of the initial Coley criteria in 1950 of ‘Lymphoma presenting in an osseous site with no evidence of disease elsewhere for at least six months after diagnosis’) 5,6 are uncommon among extranodal lymphomas. They accounts for <5% of all bone malignancies and are mostly are NHL. Secondary bone involvement in nodal NHL is uncommon, too, and typically is L Study of lymphomas of the bone and musculoskeletal system Z Al-Barazanchi, J Al-Ali & A Abbadi Bas J Surg, June, 20, 2014 27 restricted to aggressive types where the lesions are usually lytic 7 . For staging purposes, involvement of bone only is regarded as stage I, while involvement of bone along with other sites, or secondary to nodal disease is considered as stage IV, which differs entirely in prognosis. Diffuse large B-cell lymphoma is the most common type in both primary and secondary lymphomas. Primary bone NHL lymphomas usually arise from the appendicular skeleton or from flat bones of the axial skeleton, while secondary bone lymphomas usually involve the axial skeleton (skull, spine, ribs, and pelvis). Primary HL of the bone is very rare, whereas secondary involvement is found in 10%–25% of patients 8 . The imaging findings of bone lymphoma at conventional radiography, CT, and MR imaging are nonspecific, and usually reflect an aggressive pattern of bone destruction. It had been proved that FDG PET is more specific and sensitive than conventional bone radiology in identifying bone involvement by malignant lymphoma 8,9 . Aims of the study The study aims to clarify the incidence, epidemiology, clinical presentations, staging, classification, pathological types and hematological, biochemical, immunological alterations of lymphomas of the bone and musculoskeletal tissue (both primary and secondary) among patients from the south of Iraq. Materials and methods During the period of June 2008-February 2012, 669 newly diagnosed lymphoma patients, from Basra, Missan, Thi Qar, Muthanna, Babylon and Wasit Governorates, were studied. Of them, 347 cases had extranodal lymphomas, out of which, bone and musculoskeletal lymphomas (both primary and secondary) were 43 cases. Most of the workup had been done in the Laboratory Departments of both Basra General Hospital and Basra Children Specialty Hospital. Some of the work had been accomplished in the researcher’s Private Laboratory. All cases were subjected to a thorough clinical study including: age, gender, residency of origin (the site they were living for the last 20 years). Those from Basra, were categorized into 5 regions: City Center, North, South, and East and West (Table I). Table I: Geographical divisions of Basra Governorate adopted Territory Included Areas Center All districts and avenues within the official boundaries of City Centre. North Garma, Hartha, Daer, Qurna, Midaena, Talha. East Shatt-Al-Arab, Nashwa. west Shiaeba, Safwan. South Zubair, Um Qasir, Fao, Abul-Khaseeb. Patients were segregated into rural or urban in origin depending on whether they at live, for the last 5 years, in rural or urban areas. The smoking habit, the duration of smoking and the number of cigarettes consumed per day were asked for. The drinking habit was asked for, too. A history of a possible exposure to radiation (a direct exposure to a blast or war explosion, the presence of suspected war remnants in the vicinity of residence for > 5 years, or, the direct exposure to radiation in the form of therapy for another disease) was asked for. A positive family history of any malignant disease (affecting the 1stdegree relatives) and the type of the tumor was ascertained too. The chief complaint and duration of illness (in months) were inquired for. The presence of "B" symptoms: an increase in body temperature >37.3 °C for >10 days Study of lymphomas of the bone and musculoskeletal system Z Al-Barazanchi, J Al-Ali & A Abbadi Bas J Surg, June, 20, 2014 28 (matched with measuring body temperature by examination), any drenching sweating especially at night, and loss of >10 % of body weight over a period of 3 months, were asked for 10 . The same was done for the presence of intense itching, any change in bowel habit and any history of a bleeding tendency. The general status of the patient was assessed, according to the Eastern Cooperative Oncology Group Performance Status (Table II) 11 . Table II: The Eastern Cooperative Oncology Group Performance Status (11). Grade Description 0 Fully active, able to carry on all pre-disease performance without restriction. 1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (eg, light housework, office work). 2 Ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours. 3 Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4 Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5 Dead. Patients were examined thoroughly for the presence of fever (by measuring the core temperature of the patient at the time of initial presentation), pallor, jaundice, hepatomegaly, splenomegaly (the last two were matched with the findings on abdominal ultrasound examination), neurological and cutaneous manifestations, ecchymotic patches anywhere or any evidence of a bleeding tendency, the presence of palpable lymphadenopathy and their sites. An enlargement of any two or more groups of the non-contiguous groups above was considered to be "generalized" 12 . All the patients were subjected to chest radiographs and abdominal ultrasound examinations and then were staged using the Ann Arbor Classification System 13 into 4 stages: I, II, III and IV. All patients were subjected to hematological investigations, including full blood count, using the BeckmanCoulter 5 differential hematology analyzer which was properly calibrated according to the manufacturer's instructions with quality controls included between batches 14 , erythrocyte sedimentation rate (ESR) (Westergren method) 15 , peripheral blood smear examination to find the presence of abnormal lymphoid/leukemic peripheral blood cells, bone marrow aspiration, touch imprint and trephine biopsy (Figure I). Both direct and indirect antigolobulin tests (DAT & IAT) were done, too 16 . Normal results used were those adopted by the International Council of the Standardization in Hematology (ICSH) and the British Committee for Standardization in Haematology (BCSH) 17,18 . For those with palpable, accessible lymph nodes, fine needle aspiration was performed, stained with haematoxylin stain 19 and examined. Hodgkin lymphomas were classified according to the original Rye classification since it is popular among both pathologists and clinicians for its simplicity, ease of use, the association of individual types with prognostic differences when treated with current therapy and because of the lack of immunophenotypic studies 20 , while the non-Hodgkin's lymphomas were classified using the International Working Formulation because of the lack of cytogenetic, immunological and molecular studies 21,22 . Patients were subjected to a battery of biochemical tests including: liver function Study of lymphomas of the bone and musculoskeletal system Z Al-Barazanchi, J Al-Ali & A Abbadi Bas J Surg, June, 20, 2014 29 and renal function tests, serum uric acid, calcium, lactate dehydrogenase (LDH), beta-2-microglobulin 23-33 and serological tests including the anti gliadin antibodies (AGA), anti tissue transglutaminase (ATTA), anti Epstien-Barr virus (EBV) antibodies and anti Helicobacter pylori a