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Frequency and pattern of bone marrow infiltration in Hodgkin's lymphoma.

Byline: AYAZ LONE AND SAMINA NAEEM

ABSTRACT

Introduction: Lymphomas are malignant neoplasms arising from lymphoid tissue. They are divi- ded into two groups i.e Hodgkin's Lymphoma and Non-Hodgkin's Lymphoma. Staging of Hodg- kin's Lymphoma is important for the management and treatment of the patient. This study was carried out to determine the frequency of bone marrow infiltration at the time of diagnosis as well as various patterns of bone marrow involvement.

Materials and Methods: Clinical history and physical findings were recorded in the proforma. Investigations were carried out. Bone marrow aspirate and trephine biopsies were performed from posterior iliac crest. Aspirates and trephine biopsies were evaluated and assessed for cytolo- gy, marrow architecture, haemopoietic tissue and any lymphomatous infiltration. In cases with in- filtration, the infiltration pattern was studied.

Results: Fifty Hodgkin's lymphoma patients were studied. Bone marrow infiltration was found in 19 (38%) cases. Among these 19 patients with infiltration 17 (89.4%) patients were of Hodgkin's Ly- mphoma mixed cellularity and 2 (10.5%) had Hodgkin's Lymphoma Nodular Sclerosis. Pattern of infiltrate was interstitial in majority of cases followed by diffuse type of infiltration.

Conclusion: Bone marrow involvement in Hodgkin's Lymphoma is more common in our setup as patients present at a later stage. It is recommended that bone marrow examination should be per- formed as a part of staging investigations in patients with Hodgkin's Lymphoma.

Key Words: Hodgkin's Lymphoma (HL), bone marrow infiltration.

INTRODUCTION

Lymphomas are malignant neoplasms characterized by the proliferation of cells native to the lymphoid tissue. They are divided into two broad groups, Ho- dgkin's lymphoma (HL) and non-Hodgkin's lymph- oma (NHL). HL is characterised morphologically by the presence of neoplastic giant cells the Reed - Ste- rnberg (RS) cells admixed with a variable inflamma- tory infiltrate.

RS cells express CD30 and CD15 antigens. Hodgkin's lymphoma was first described in 1832.1 In adult population the incidence of bone marrow infil- tration in Hodgkin's lymphoma is around 10% but in paediatric population the incidence is very low (1.8%).2

HL is classified according to the WHO Classifi- cation, which is the reviewed REAL classification in- to a) Classical Hodgkin's lymphoma, which includes Nodular Sclerosis, Lymphocyte Depletion, Lympho- cyte Rich and Mixed Cellualrity HL and b) Lympho- cyte Predominance as a separate entity.3

Staging of the lymphoma is important for the management and treatment of the patient. Bone marrow trephine biopsy is one of the first investiga- tion, which is being carried out for staging4,5 along with clinical findings and other investigations like CBC, CT scanning, Ultrasonography and MRI. In many centers flow cytometry of bone marrow aspi- rates is also being used in staging.6-8

This study was conducted to see how many pati- ents presenting to us have bone marrow infiltration at the time of diagnosis. This places them in Stage IV disease, which is associated with poor prognosis. Patterns and extent of bone marrow involvement by different varieties of HL was also studied.

MATERIALS AND METHODS

This study was conducted at King Edward Medical University, department of Pathology, Lahore from January 2004 to January 2005and included all the cases from the affiliated and referring hospitals. The patients of Hodgkin's Lymphoma diagnosed on tis- sue biopsy (nodal and extra nodal) were included in the study. Patients already on treatment and relap- sed cases were not included in this study.

A detailed clinical history was taken from the patients selected, thorough clinical examination was done. Relevant investigations which included blood complete examination, urine complete examination, urea and creatinine levels, liver function tests, LDH levels, tissue biopsy, ultrasonography and CT scans were also recorded.

Bone marrow aspiration and trephine biopsy was performed from posterior Iliac crest, under local anaesthesia with mini- mal discomfort. Marrow aspirates were st- ained with Wright - Giemsa stain. Sec- tions of trephine biopsy were stained with Haematoxylin and Eosin. Assessment was made of the cytological features of cells in marrow aspirate smears. Trephine biop- sies were evaluated for architecture, ves- sels, stroma, haemopoietic tissue and pat- tern of lymphoid infiltrates (diffuse, inter- stitial, focal, nodular, focal patchy and pa- ratrabecular).

RESULTS

Among the 50 HL patients 11 were females (22%) and 39 (78%) were males. The age of the pa- tients ranged from 7 to 80 years with a mean age of 28.1 years S.D +- 17.11. Ten patients (20%) were in paediatric age group below 15 years (1 female and 9 males). Age distri- bution in male and fema- le cases is shown in figu- re 1.

Majority of the cases presented with cervical lymphadenopathy (42%) followed by generalised lymphadenopathy (12%).

Thirty nine patients (78%) had Hodgkin's ly- mphoma Mixed Cellula- rity (8 females and 31 males), 7 patients (14%) had Hodgkin's lymphoma nodular sclerosis type (3 fe- males and 4 males), 3 (6%) had Hodgkin's lymphoma Lymphocyte predominant (males) and only one (2%) case was of Hodgkin's lym- phoma lymphocyte deple- tion (male) type.

According to clinical and diagnostic work up prior to bone marrow exami- nation these patients presented in different stages of disease. Thirteen (26%) were in Stage I, 9 (18%) were in Stage II, majority of the patients, 18 (36%) were in Stage III and 10 (20%) patients were al- ready in Stage IV disease with liver involvement. B symptoms were present in 11 (22%) cases. Bone

Table 1: Frequency of bone marrow involvement in different types of Hodgkin's Lymphoma in total cases, females and males.

Types###Total Cases###Females###Males

###Bone###Bone###Bone

###Marrow###Marrow###Marrow

###Total###Involvement###Total###Involvement###Total###Involvement

###N###%###N###%###N###%

Mixed###39###17###43.5###8###4###50###31###13###41.9

cellularity

Nodular

Sclerosis###7###2###28.5###3###2###66.6###4###-###-

Lymphocyte###3###-###-###-###-###-###3###-

predominance

Lymphocyte###1###-###-###-###-###-###1###-###-

Depletion###

Total###50###19###38###11###6###54.5###39###13###33.3

Table 2: Pattern of bone marrow infiltration in different types of Hodgkin's Lymphoma.

Type###Total Cases###Interstitial###Diffuse###Focal

###with Infiltration###Infiltration###Infiltration###Infiltration

Mixed cellularity###17###10###5###2

Nodular Sclerosis###2###2###-###-

Total###19###12###5###2

Table 3: Role of bone marrow examination in staging of Hodgkin's Lymphoma

###Before Bone Man ow Exwth m tion###After Bone Marrow Examination

###TOtal###Stage###Stage

Type###No of

###Cases###I###II###III###IV###I###II###III###IV

###No###%###No###%###No###%###No###%###No###%###No###%###No###%###No###%

Mixed cellularity###39###8###20.5###5###12.8###17###43.5###9###23###8###20.5###4###10.2###7###17.9###20###51.2

Nodular###7###3###42.8###4###57.1###-###-###-###-###2###28.5###3###42.8###-###-###2###28.5

Sclerosis

Lymphocyte###3###2###66.6###-###-###1###33.3###-###-###2###66.6###-###-###1###-###-

Predominance###1###-###-###-###-###1###100###-###-###-###-###-###-###1###100

Lymphocyte Depletion###50###13###26###9###18###18###36###10###20###12###24###7###14###8###16###~23###46

Cases grouped in Stage IV because of Liver involvement

~ 4 cases didn't showed marrow infiltration. They were in Stage IV before marrow examination because of Liver involvement

marrow infiltration was found in 19 (38%) cases (6 females and 13 males).

Infiltrate comprised of eosionphils, lymphocy- tes, plasma cells, Reed Sternberg cells, and Hodg- kin's cells. Fibrotic and hypocellular marrow was also seen in some cases. Among the 19 patients with infiltration 17 (89.4%) were of Hodgkin's lymphoma mixed cellularity (4 females and 13 males) and 2 (10.5%) had Hodgkin's lymphoma nodular sclerosis type (both females) (Table 1). So bone marrow infil- tration was present in 43.5% (17 of 39) cases with mixed cellularity Hodgkin's lymphoma and 28.5% (2 of 7) of those with nodular sclerosis. Twelve pati- ents (63%) had interstitial infiltration with back- ground fibrosis, 5 (26%) had diffuse pattern of infil- tration with fibrosis and 2 (10%) patients had focal infiltration (Table 2). Bone marrow aspirates of 10 patients showed prominence of lymphocytes, plas- ma cells, eosinophils with occasional atypical mono- nuclear cells. Only 2 patients with these findings on aspirates had lymphoma cell infiltration in marrow on trephine biopsy.

DISCUSSION

The objective of present study was to determine the frequency of bone marrow involvement in different clinical stages and histological types of Hodgkin's Lymphoma. The present study reflects the growth and invasive potential of Hodgkin's lymphomas in our population. All the cases included in this study were already categorised and typed by immunohis- tochemistry either from Agha Khan Hospital, Kara- chi or Shaukat Khanum Memorial Cancer Hospital, Lahore.

A total of 50 cases of Hodgkin's lymphoma were investigated for frequency and pattern of bone mar- row infiltration. Among these 19 (38%) had bone marrow infiltration at the time of diagnosis, which placed them in Stage IV disease. Mixed cellularity Hodgkin's lymphoma was the most common histo- logical type and showed marrow involvement in 43.5% (17 of 39) cases. This was followed by nodular sclerosis 28.7% (2 of 7) cases. Study carried out at Agha Khan University Hospital Karachi showed that Mixed Cellularity Hodgkin's lymphoma is more pre- valent in our population,9 this is similar to our stu- dy. In adult population the incidence of bone mar- row infiltration is estimated between 2 - 32%.2 Bo- ne marrow involvement represents Stage IV disease i-e disseminated involvement of an extra nodal or- gan.

The study carried out by Fauzia et al1 showed bone marrow infiltration in 27.5%, the frequency was higher in females i.e 57% as compared to males showing 21.9%. Infiltration of bone marrow was seen most commonly with mixed cellularity Hodg- kin's Lymphoma. Study carried out by Sharma10 showed a much higher incidence of bone marrow involvement. In his study bone marrow infiltration was present in 36.2% cases. Most of the cases were in Stage III and Hodgkin's Disease mixed cellularity showed highest incidence of marrow involvement. In our study the frequency of marrow infiltration is also high (38%) and majority of the cases are of mi- xed cellularity Hodgkin's lymphoma. Patients in Pa- kistan present late for treatment because of lack of resources or ignorance. Lei K et al11 studied 6 cases and only one was in Stage IV, giving a percentage of 16.6%. In another local study carried out by Akram et al12 bone marrow infiltration was seen in 21.3% cases.

Ananthamurthy13 in his study found infiltra- tion of the marrow in 20% cases at the time of diag- nosis with marrow suppression, fibrosis and lym- phocytes aggregates.

In the present study after the bone marrow tre- phine biopsy 1 patient was in Stage I, 2 in Stage II, 10 patients III and 6 patients stage IV showed bone marrow infiltration. Four patients who were in Sta- ge IV disease prior to bone marrow examination be- cause of liver involvement didn't show bone marrow infiltration (Table 3). All the corresponding bone marrow aspirates were negative for infiltration and this showed that biopsies are superior to aspirates for the diagnosis of infiltrate in Hodgkin's lympho- ma. In our study only two corresponding bone mar- row aspirates were also positive for infiltration on trephine biopsy and eight were negative on bone biopsy. Another study showed infiltration in 17.1% cases.14 Study reported at King Edward Medical University, Lahore showed bone marrow infiltration of Hodgkin's lymphoma in 30% of cases.15

In the present study females showed a much hi- gher incidence 54.5% (6 of 11) of bone marrow infil- tration despite less number of cases as compared to males. This is probably because we have a male do- minated society and females are brought to hospital at a much later stage of disease. Higher incidence could be because most of the patients with infiltra- tion were already in stage III.

In conclusion bone marrow involvement in Hodgkin's Lymphoma was seen in CS II and beyo- nd, therefore it is recommended that bone marrow examination may be performed as a part of staging investigations in patients with Hodgkin's lymphoma when it is CS II or high. Due to poor economic con- ditions, lack of awareness and treatment facilities in rural areas these patients come at a late stage of disease.

REFERENCES

1. Butt F, Akhtar R, Rahmani T, Waheed A, Aman S, Hamid S. Bone marrow involvement in lymphoma: Incidence and co-relation with age and sex. Biome- dica 2002; 18: 53-57.

2. Franco V, Tripodo C, Rizzo A, Stella M, Florena AM. Bone marrow biopsy in Hodgkin's Lymphoma. Euro- pean journal of haematology 2004; 73 (3): 149-155.

3. P G Lssacson. The current status of lymphoma classi- fication. Br J Haematol 2000; 109: 258-266.

4. Howell SJ, Grey M, Chang J, Morgenstern GR, Co-wan RA, Deakin DP et al. The value of bone marrow examination in the staging of Hodgkin's lymphoma: a review of 955 cases seen in a regional cancer center. Br J Haematol 2002; 119: 408-411.

5. Subramanian R, Basu D, Badhe B, Dutta TK. Role of bone marrow trephine biopsy in the diagnosis of marrow involvement in Hodgkin's disease. Indian J Pathol Microbiol. 2007; 50 (3): 640-643.

6. Goldschmidt H, Wallmeier M, Hegenbrat U, Haas R. Malignant lymphoma. Pathology, diagnosis, therapy. Radiologe 1997; 37 (1): 1-9.

7. Palacio C, Acebedo G, navarrete M, Ruiz - Marrcel- lan C, Sanchez C, Blanio A, Lopez A. Flow cytometry in the bone marrow evaluation of follicular and dif- fuse large B-cell lymphoma. Haematologica 2001; 86 (9): 934-940.

8. Vinnicombe SJ, Reznek RH. Computerised topogra- phy in the staging of Hodgkin's disease and NHL. Eur J Nucl Med Mol Imaging 2003; 30(Suppl 1): S 42-55.

9. Siddiqui T, Pervez S. Spectrum of Hodgkin's disease in children and adults: impact of combined morpho- logic and phenotypic approach for exclusion of "look- alikes". J Pak Med Assoc 1999; 49 (9): 211 - 214.

10. Sharma S, Ahiya A and Murari M. Bone marrow bio- psy in Hodgkin's disease. Indian J Pathol Microbiol 2004; 47 (3): 346-347.

11. Lei K I, Chan L Y S, Chan W Y, Johnson P J and Den- nis Y M. Quantitative analysis of circulating cell free Epstein - Barr Virus (EBV) DNA levels in patients with EBV associated lymphoid malignancies. Br J Haematol 2000; 111: 239-246.

12. Armitage JO. Staging Non-Hodgkin's lymphoma. CA Cancer J Clin 2005; 55: 368-376.

13. Ananthamurthy A, Kurien A, Ramnarayan K. The bo- ne marrow in Hodgkin's disease - a two year study. Indian j Cancer 2000; 37 (4): 173-83.

14. Nadeem M, Naqi N, Hussain I, Khattak J, Ahmed R and Khan B. Frequency of bone marrow involvement in Hodgkin's Lymphoma on first presentation. J Coll Physicians Surg Pak 2009; 19 (12): 768-771.

15. Hamid A, Hamid Am, Jabbar N, Naeem S. Signifi- cance of bone marrow biopsy in staging of Hodgkin's Lymphoma. Annals of King Edward Medical Univer- sity 2010; 16 (1): 12-16.

1Department of Haematology, Fatima Memorial Hospital College of Medicine and Dentistry, 2Department of Pathology, King Edward Medical University, Lahore - Pakistan
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Author:Lone, Ayaz; Naeem, Samina
Publication:Biomedica
Article Type:Clinical report
Geographic Code:9PAKI
Date:Dec 31, 2011
Words:2471
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