Clinico-pathological analysis of lymphoproliferative disorders: a 3 year study

Background: The incidence of lymphoproliferative disorders has increased in many parts of the world. Newer subtypes have been identified by the new WHO classification. Accurate subtyping of lymphomas is crucial for prompt treatment. Objective of the study was to assess the clinicopathological pattern of lymphoproliferative diseases diagnosed in Rajagiri hospital over a period of 3 years.Methods: A retrospective study on all patients who were diagnosed with lymphoma in Rajagiri hospital during January 2016 to December 2018 was conducted and the data were reviewed and analyzed.Results: A total of 151 patients were included in the study. Majority of the subjects (63%) were males. The predominant age group affected was 61-80 years. Mean age group was 58.46 years (SD=19.05 years). Most common presenting symptom was painless lymphadenopathy. B symptoms were seen in 18% of subjects and was found to be more commonly associated with B cell Non-Hodgkin lymphoma. Most common lymph node involved was cervical lymph node, while the most common extra nodal site was bone marrow. Most common lymphoproliferative disorder was Diffuse large B cell Lymphoma. Lymph node involvement was found in 74% of patients, while hepatomegaly and splenomegaly were seen in 11% and 18.5% of patients. 20% of patients had secondary bone marrow involvement. 8 patients developed recurrent lesions involving other organs.Conclusions: Clinicopathologic patterns of lymphoproliferative disorders vary across various regions. A proper understanding of demographical distribution of lymphomas is very essential, as it can provide valuable clues for accurate diagnosis and treatment.

Cluster Containing More Than 20 CD3-Positive Cells in Bone Marrow Biopsy Is a Candidate Prognostic Indicator in Peripheral T-Cell Lymphoma, Not Otherwise Specified

Assessment of bone marrow (BM) involvement in peripheral T-cell lymphoma, not otherwise specified (PTCL) is straightforward in cases of extensive involvement but difficult in cases of minimal to partial involvement. We evaluated the usefulness of CD3 as an immunohistochemical marker for assessing BM involvement in PTCL patients. BM biopsies of 92 PTCL patients were immunohistochemically stained for CD3, CD4, CD8, CD20, and CD56, and evaluated by two hematopathologists. CD3 positivity was graded according to the proportion of CD3-positive cells and the number of CD3-positive cells in a cluster. These criteria were used to determine the cut-offs at which significant differences in progression-free survival (PFS) and overall survival (OS) were observed. Multivariate analysis controlling the International Prognostic Index (IPI) score and its individual factors revealed that >20 CD3-positive cells in a cluster adversely affected PFS (relative risk [RR], 2.1; 95% confidence interval [CI], 1.0–4.3; P=0.047) and OS (RR, 2.4; 95% CI, 1.1–5.1; P=0.028) independent of IPI score. A cluster with >20 CD3-positive cells is a candidate indicator for BM involvement in PTCL.

Detection of bone marrow involvement with FDG PET/CT in patients with newly diagnosed lymphoma

BACKGROUND: Bone marrow involvement (BMI) affects the lymphoma stage, survival, and treatment. Bone marrow biopsy (BMB) and fluorodeoxyglucose (FDG) positron emission tomography- computed tomography (PET/CT) are useful techniques to detect BMI. Both have advantages and disadvantages. We aimed to identify factors that could be used to predict BMI with positive and negative results on PET/CT compare them with BMB in newly diagnosed patients with lymphoma. METHODS: We included 22 non-Hodgkin and 16 Hodgkin lymphoma patients in this single center study. All patients had PET/CT examination and BMB before treatment. BMI in BMB was reported as negative or positive. Bone marrow was classified into 3 types by FDG uptake on PT/CT; diffuse involvement, focal involvement, and normal bone marrow. RESULTS: PET/CT and BMB results were concordant (7 positive, 15 negative) in 22 patients (57%). We evaluated concordant and discordant patient characteristics and risk-stratified patients for BMI. Our findings suggest that patients with diffuse FDG uptake on PET/CT, especially patients with advanced age and low platelet and white blood cell counts, are likely to have BMI and could potentially forego BMB. Patients with negative PET/CT findings and no significant laboratory abnormalities are very unlikely to have BMI. CONCLUSION: Our results suggest that BMI should not be decided solely based PET/CT or BMB findings. It is reasonable to use both diagnostic assays along with clinical and laboratory findings. PET/CT result, clinical and laboratory findings could be useful for predicting BMI in patient for whom BMB is contraindicated.

Prevalence and Implications of Bone Marrow Involvement in Patients with Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

BACKGROUND/AIMS: Mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach is an uncommon disease. Bone marrow involvement is reported even in patients with only a mucosal lesion. We evaluated the prevalence and risk factors of marrow involvement and its implications for diagnosis and treatment. METHODS: In total, 132 patients who were diagnosed with gastric MALT lymphoma at the National Cancer Center in Korea between January 2001 and December 2016 were enrolled in the study. The patient data were collected and analyzed retrospectively. RESULTS: Of the 132 patients, 47 (35.6%) were male, with a median age of 52 years (range, 17 to 81 years). The median follow-up duration was 48.8 months (range, 0.5 to 169.9 months). Helicobacter pylori infection was detected in 82 patients (62.1%). Most patients (80.3%) had stage IE1 according to the modified Ann Arbor staging system. Ninety-two patients underwent bone marrow evaluation, and four patients (4.3%) had marrow involvement. Of these patients, one presented with abdominal lymph node involvement, while the other three had stage IE1 disease if marrow involvement was disregarded. All three patients had no significant symptoms and were monitored after local treatment without evidence of disease aggravation. CONCLUSIONS: Bone marrow involvement was found in 4.3% of the patients with gastric MALT lymphoma. Bone marrow examination may be deferred because marrow involvement does not change the treatment options or outcome in gastric MALT lymphoma confined to the stomach wall.

Differential diagnosis of diffuse bone marrow uptake on 18F-FDG PET/ CT

Background: Bone marrow is a frequent site of metastatic tumors, especially from breast, lung, and prostate cancers. Metastatic tumor in the bone marrow may influence the response to treatment, overall survival, and resulting decreased hematopoiesis. Diffusely and homogenously bone marrow uptake in 18F-FDG PET/CT scan is frequently observed which can caused by many conditions. Material and methods: We retrospectively analyzed the consecutive records of F-18 FDG PET scans performed from April 2011 to August 2013 at Mochtar Riady Comprehensive Cancer Center Siloam Hospital, A total of 2952 result were reviewed. 16 patients with diffusely and homogenously bone marrow uptake in F-18 FDG PET/CT whole body scan between January 2012 and December 2013 were evaluated to find out the etiology. Results: From 2952 patients performed 18F-FDG-PET/CT there are 16 patients (5 men, 11 women) with diffusely and homogenously increased FDG uptake in bone marrow, mean age: 52 years, range 5–82 years. It was found that 6 of 16 FDG PET/ CT positive patient with solid tumors and 10 of 16 FDG PET/CT with non solid tumors. Malignancy was observed in 14 patients and benign in 2 patients. Diffusely and homogenously uptake due to 1 patiets with Idiopathic thrombocytopenic purpura (ITP) , 6 patient with anaemia, 7 patients with chemotherapy, 1 patients with Granulocyte Colony-Stimulating Factor (G-CSF) and 1 patients with extra-nodal non-hodgkin lymphoma were observed. Conclusion: Diffusely and homogenously increase bone marrow on 18F FDG PET/ CT whole body scan uptake can be seen in malignant or benign disease and history of treatment. Spleen uptake are observed at the initial imaging than bone marrow involvement while spleen uptake more frequently reflects disease involvement.

The analyse of examining the bone marrow involvement in ninety-three patients of non-Hodgkin′s lymphoma / 国际检验医学杂志

Objective To explore the value of combined detection of bone marrow smear(BMS) and flow cytometry(FCM) to examine bone marrow involvement(BMI)of B cell non‐Hodgkin′s lymphoma(B‐NHL) .Methods Patients with B‐NHL were detec‐ted by BMS and FCM simultaneously .Smears were stained with Wright‐Giemsa′s staining to differentially count neoplastic cells and the processed sample with fluorescent staining for the FCM .Results 93 cases of patients with B‐NHL were detected .The detection rate of BMS and FCM were 11 .8% and 29 .0% .There was statistical difference of detection rate between the two method(P<0 .05) .In 11 cases patients of BMI with the method of BMS ,while using the method of FCM 10 cases were positive .Conclusion Both BMS and FCM are useful to diagnose BMI of B‐NHL ,each of them has individual characteristics .Combined detection of these two methods can increase the diagnostic of BMI .

Assessment of bone marrow involvement in patients with lymphoma: report on a consensus meeting of the Korean Society of Hematology Lymphoma Working Party

In September 2011, the Korean Society of Hematology Lymphoma Working Party held a nationwide conference to establish a consensus for assessing bone marrow (BM) involvement in patients with lymphoma. At this conference, many clinicians, hematopathologists, and diagnostic hematologists discussed various topics for a uniform consensus in the evaluation process to determine whether the BM is involved. Now that the discussion has matured sufficiently to be published, we herein describe the consensus reached and limitations in current methods for assessing BM involvement in patients with lymphoma.

Case series of precursor B-cell lymphoblastic lymphoma

Precursor B-cell lymphoblastic lymphoma (B-LBL) is an uncommon subtype of Non-Hodgkin lymphoma (NHL), accounting for only 0.3% of NHL in adults and less than 10% of all LBL cases. Unlike T-cell LBL, it usually presents with extranodal involvement while sparing the bone marrow (BM). Among the 27 patients with LBL treated in the Asan Medical Center between January 2007 and March 2012, 3 had B-LBL. All had a good performance status and low International Prognostic Index. However, unlike most previously reported cases, the patients had lymphoma in their bone marrow and extranodal sites such as bone and lung. After intensive combination chemotherapy, one patient achieved a complete response and the other 2 patients, a partial response. Our experience suggests that multiple extranodal sites may be involved in B-LBL and BM involvement may not be as infrequent as previously thought. Furthermore, intensive chemotherapy seems to be effective.

Clinical observation of four-weekly pirarubicin combined with COP regimen in aggressive non-Hodgkin lymphoma patients with bone marrow involvement / 白血病·淋巴瘤

Objective To evaluate the clinic efficacy and adverse effects of four-weekly pirarubicin combined with COP (CTOP-28) regimen in aggressive non-Hodgkin lymphoma patients with bone marrow involvement. Methods 65 aggressive non-Hodgkin lymphoma cases with bone marrow involvement (BMI)from January 2002 to January 2007 were chosen, who were newly diagnosed according to 2001 World Health Organisition (WHO) classification. The response rate and adverse effects of CTOP-28 regimen were retrospectively compared with standard CHOP-21 regimen in these patients. CHOP-21 regimen:eyclophosphamide 750 mg/m2(day 1), vincristine 1.4 mg/m2 (maximum 2 rag, day 1), adrimycin 50 mg/m2 (day1), prednisene 100 nag (day 1 to 5). CTOP-28 regimen: cyclopbosphamide 750 mg/m2 (day 1, 15), vincristine 1.4 mg/m2 (maximum 2 rag, day 1,8,15,22), pirarubicin 25 mg/m2 (day 1,2 and 15,16), prednisone 40 mg/m2(day 1 to 28). Results The complete remission rate (CRR) in CHOP-21 group was less than in CTOP-28group (40 % vs 80 %, P＜0.05). The incidence of 3 and 4 degree blood toxicity in CTOP-28 was more than in CHOP-21 (100.0 % vs 50.0 %, P ＜0.05), but incidence of 1 and 2 degree cardic toxicity was similar as CHOP-21 (8.57 % vs 10.0 %, P＞0.05) and 3 and 4 degree cardic toxicity did not occurred in both groups.The gastrointestinal, hepatobiliary and renal toxicities at only 1 and 2 degree took place and no difference wasfound between two groups. No therapy-related mortality occurred in these patients. Conclusion CTOP-28regimen is more effective, safer for aggressive non-Hodgkin lymphoma patients with BMI as induction treatment.

A Case of CD30 Positive ALK-Negative Systemic Anaplastic Large Cell Lymphoma Involving Bone Marrow / 대한피부과학회지

CD 30 positive anaplastic large cell lymphoma (ALCL) is a type of non-Hodgkin's lymphoma, a tumor that is composed of mostly mast cells expressing CD30 antigens. According to the 2005 World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) classification, it can be classified as systemic ALCL and primary cutaneous CD30 positive T-cell lymphoproliferative disorder. Systemic ALCL can be subclassified into ALK positive and negative. There have been many cases of primary cutaneous CD30 positive T-cell lymphoproliferative disorder, but reports of systemic ALCL have been rare. We report a case of CD30 positive/ALK negative systemic anaplastic large cell lymphoma involving bone marrow in a 51 year-old-male who showed two pruritic, 1.5x1.0x0.8 cm and 1.0x0.5x0.4 cm sized, erosive, erythematous nodules on the right thigh and calf.

Incidence and Histologic Patterns of Bone Marrow Involvement of Malignant Lymphoma Based on the World Health Organization Classification: A Single Institution Study / 대한진단검사의학회지

BACKGROUND: Working Formulation and Revised European American Classification of Lymphoid Neoplasms (REAL) have mainly been used in the studies for bone marrow involvement of malignant lymphoma in Korea. We investigated the incidence and histologic patterns of malignant lymphoma according to the WHO classification. METHODS: This study included 507 cases of malignant lymphoma that were requested for bone marrow study for the staging during the period January 1999-December 2005 in Korea Cancer Center Hospital. Medical records, peripheral blood smears, bone marrow aspiration smears, biopsy sections, and histopathologic findings were analyzed retrospectively. RESULTS: Of the 507 cases of malignant lymphoma, 473 (93.3%) were non-Hodgkin lymphoma (NHL) and 34 (6.7%) were Hodgkin lymphoma (HL). The overall incidence of bone marrow involvement by NHL and HL was 12.5% (59/473) and 11.8% (4/34), respectively. Among NHL cases, the incidence of bone marrow involvement by B-cell and T-cell neoplasms was 11.4% (43/377) and 16.7% (16/96), respectively. Although the incidences of bone marrow involvement by several B-cell neoplasms were more than 30%, diffuse large B cell lymphoma showed a relatively low incidence of bone marrow involvement (4.6%). Of bone marrow involvement patterns, diffuse infiltration pattern was the most common (40.0%). Peripheral blood involvement by lymphoma was observed in 35.6% of cases with bone marrow involvement. CONCLUSIONS: We used WHO classification in the study for the bone marrow involvement of malignant lymphoma, and this single-institution study should give a useful, up-to-date histopathologic information.

A Case of Hodgkin`s Lymphoma with Bone Marrow Involvement Showing Severe Osteosclerosis / 대한진단검사의학회지

Bone marrow involvement in Hodgkin`s lymphoma is not rare at initial diagnosis and is associated with a poor prognosis. Atypical findings such as granuloma, eosinophilia or osteosclerosis may lead to diagnostic confusion, in which case immunohistochemistry may be helpful. We report a case of 25-year old male patient, who presented with back pain, subsequently had a mediastinal mass and was finally diagnosed as having stage IV Hodgkin`s lymphoma. Bone marrow involvement with severe osteosclerosis was found on bone marrow biopsy specimens. He received systemic chemotherapy and was discharged with improved clinical symptoms.

Bone Marrow Involvement of Primary Mediastinal Germ Cell Tumor: A Case Report / 대한임상병리학회지

A variety of solid tumors can metastasize to bone marrow. In rare cases actual circulating neoplastic cells can be identified, accounting for usually only a low proportion of total white blood cells. It is well known that hematologic malignancies are often associated with mediastinal germ cell tumors, but huge tumor cell burden resulting in leukemia-like presentation is a very rare manifestation. We report here a case of malignant germ cell tumor with leukemia-like infiltration of bone marrow. A 19-year-old man was admitted for dyspnea for several months. Computer tomographic scan revealed that he had a huge mass at anterior mediastinum with a large amount of pleural effusion. His pleural fluid had many numbers of large, pleomorphic atypical cells. Peripheral blood also contained atypical cells with similar morphology. On bone marrow biopsy, diffuse infiltration of tumor cells were noted suggesting acute leukemia, but immunophenotyping ruled out the possibility of hematologic malignancy. His serum alpha-fetoprotein and beta-human chorionic gonadotropin levels were markedly elevated, which was consistent with the diagnosis of primary germ cell tumor. Cytogenetically the tumor cells showed hyper-triploidy. After induction chemotherapy with cisplatin, etoposide and bleomycin, the size of the tumor was regressed and the patient's symptoms were improved.