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| Year : 2008 | Volume
: 51
| Issue : 3 | Page : 451-453 |
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| Lymphoid aggregates in bone marrow biopsies in patients with hypereosinophilia |
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Seema Sharma, Neeraj Dhameja
Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Click here for correspondence address and email
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How to cite this article:
Sharma S, Dhameja N. Lymphoid aggregates in bone marrow biopsies in patients with hypereosinophilia. Indian J Pathol Microbiol 2008;51:451-3 |
Sir,
Hypereosinophilia is a common finding in a number of disease states, including atopic conditions and hypersensitivity responses, such as allergies, asthma, eczema, allergic drug reactions and helminth infection, sarcoidosis, collagen vascular disease, human immunodeficiency virus infection and some tumors. [1],[2] The hypereosinophilic syndrome (HES) is a heterogeneous group of rare disorders characterized by prolonged peripheral blood and tissue eosinophilia (total eosinophil count ≥1.5 × 10 9 /L without known cause lasting for at least 6 months) leading to end-organ damage. [3] Some cases of HES represent a myeloproliferative disorder considered to be an autonomous proliferation of eosinophils, while some cases of unexplained eosinophilia result from cytokine reaction by abnormal Th2 cells that express interleukin-5 (IL-5). [4],[5],[6]
Reactive lymphoid aggregates in bone marrow (BM) biopsy are usually seen in old age, in association with infection, inflammation, myeloproliferative disorders, hemolysis and autoimmune diseases such as rheumatoid arthritis and thyrotoxicosis [7] Association of lymphoid aggregates with hypereosinophilia is not a common finding. [8]
We report two patients with hypereosinophilia in whom lymphoid aggregates were present in the BM biopsy; and believe that this is the second report of this type.
Case 1: A 27-year-old male had a history of recurrent episodes of bleeding per rectum associated with loose motions since February 2004. Six months after the onset of diarrhea, the patient developed ascites. Ascitic fluid examination revealed high total leukocyte count with predominance of eosinophils. USG abdomen done at this time showed mild coarse echotexture of the liver. The patient was put on aldactone and antitubercular therapy (ATT four drugs).
Subsequently, ascites was resolved within 6 months and the patient was put on two ATT drugs. In October 2006, the patient again developed diarrhea and bleeding per rectum, aphthous ulceration in the mouth, uveitis and left leg deep-vein thrombosis. Blood examination at this time revealed high total leukocyte count with increased eosinophils. The patient was treated with higher antibiotics and steroids; initially the patient responded, but due to persistent high TLC, the patient was referred to our hospital.
His hematological parameters at the time of admission were hemoglobin value of 77 g/L, platelet count of 252 × 10 9 /L and total leukocyte count of 61 × 10 9 /L, with a differential leukocyte count of N31, L12, E56, M1 (absolute eosinophil count 34.16 × 10 9 /L). Peripheral blood smear examination for parasite and stool examination for ova, cyst, or larvae of parasites were negative. Ultrasound revealed mild hepatosplenomegaly, ascitis and right-sided pleural effusion. His autoimmune work-up revealed ANA and c-ANCA positive in high titer and test for antiphospholipid anticoagulant (APLA) was negative. Ascitic and pleural fluid analysis showed predominance of eosinophils. Colonoscopic biopsy showed eosinophilic colitis. The patient was put on steroid, antibiotic and acitrom. His TLC reduced to 30 × 10 9 /L, but eosinophilia persisisted and DLC showed 32% eosinophils (AEC 9.6 × 10 9 ).
Case 2: A 25-year-old male patient had past history of rheumatic fever, severe mitral stenosis and moderate pulmonary arterial hypertension. Mitral valve balloon dilation was done in May 2001. In October 2006, the patient presented with pain in joints of upper and lower limbs for 1 months, burning sensation in palms and soles for 1 month and evening rise of temperature. The patient was on Penidure LA, i.m. 3-weekly. On examination, there was no organomegaly or lymphadenopathy. His blood examination revealed hemoglobin 127 g/L, platelet count 251 × 10 9 /L, total leukocyte count 29.8 × 10 9 /L, DLC N15, L11, E72, M 2 (AEC 21.45 × 10 9 /L). Peripheral blood smear examination for parasite and stool examination for ova, cyst, or larvae of parasites were negative. He was given steroid 50 mg o.d. for 3 weeks. His fever subsided and TLC reduced to 15.6 × 10 9 /L and DLC showed 4% eosinophils. However, after 2 months, he again developed fever with evening rise of temperature, ELISA test for gamma IFN and PPD was found to be positive and ATT was started. His fever did not subside and he lost weight. CT scan showed multiple mesenteric lymphadenopathy and subsplenic abscess. US-guided FNA aspirated pus was positive for AFB. His ATT was continued and fever subsided after 15 days.
In both the cases, BM aspiration and biopsy were done for persistent eosinophilia to rule out eosinophilic leukemia, myeloproliferative disorders and lymphomatous infiltration.
Bone marrow aspirate and a trephine biopsy specimen were taken from the posterior iliac crest. The BM trephine biopsy specimens in each case comprised a single core measuring 10 × 2 mm. BM biopsies in each case showed hypercellular marrow with myeloid hyperplasia. Eosinophils and their precursors were increased in number (~40-50%); however, blasts were <5%. Erythropoeisis was reduced, but maturation was normoblastic. Megakaryocytes were increased in number.
Small lymphoid nodules were seen in biopsies from both the cases. In the first case, three small-sized, discrete lymphoid aggregates were seen, while in the second case, a single aggregate of moderate size was seen. The lymphocytes within the lymphoid aggregates were small, mature cells without clefting or nucleoli. There was a mild increase in the reticulin in aggregates. Immunohistochemistry showed a mixed population of B (CD20) and T (CD3) cells, with a predominance of B cells in the first case and predominance of T cells in the second case [Figure 1].
Our first patient met the criteria of HES as he had prolonged eosinophilia, eosinophilic infiltration of the marrow and gastrointestinal tract and deep vein thrombosis. The second patient had hypereosinophilia of unexplained cause, but the duration of eosinophilia could not be ascertained as no previous records were available.
The predominant BM finding in HES is increased eosinophils and their precursors. The presence of lymphoid nodules in patients with HES is unusual. We came across a single case report by Metz et al. [8] of T-cell lymphoid aggregates in BM in idiopathic HES. In a study by Thiele et al , [7] none of the 352 patients with non-neoplastic lymphoid aggregates in BM biopsies had hypereosinophilia.
Metz et al concluded that the lymphoid aggregates within the BM biopsy represent polyclonal T-cell expansion on the basis of immunohistochemistry and absence of clonal rearrangement of the T-cell receptor 'λ locus in the peripheral blood. The mechanism of T-cell proliferations inducing eosinophilia is likely through cytokine production like granulocyte - macrophage colony stimulating factor (GM-CSF), IL-3,and Interleukin-5 (IL-5). [8]
The presence of lymphoid aggregates in bone marrow might be an incidental finding and the lymphoid aggregates might represent nodules that would be encountered in normal trephine biopsies or in chronic infections. This seems unlikely as both the patients were young and in view of the number of aggregates in the first case and the predominance of T cells in lymphoid aggregates in the second case. Association of lymphoid aggregates in BM in hypereosinophilia is rarely reported. It is important to follow-up on these patients, as some of the patients with HES may have an abnormal T-cell clone and may terminate in T-cell lymphoma. [5]
 References | |  |
| 1. | Tefferi A, Patnaik MM, Pardanani A. Eosinophilia: Secondary, clonal and idiopathic. Br J Haematol 2006;133:468-92  [PUBMED] [FULLTEXT] |
| 2. | Fauci AS, Harley JB, Roberts WC, Ferrans VJ, Gralnick HR, Bjornson BH. NIH conference, The idiopathic hypereosinophilic syndrome: Clinical, pathophysiologic and therapeutic considerations. Ann Intern Med 1982;97:78-92, [PUBMED] |
| 3. | Chusid MJ, Dale DC, West BC, Wolff SM. The hypereosinophilic syndrome: Analysis of fourteen cases with review of the literature. Medicine 1975;54:1-27. [PUBMED] |
| 4. | Bain B J. Eosinophilia-Idiopathic or not. N Eng J Med 1999;341:1141-3. |
| 5. | Simon HU, Plotz SG, Dummer R, Blaser K. Abnormal clones of T cells producing interleukin-5 in idiopathic eosinophilia. N Engl J Med 1999;341:1112-20 |
| 6. | Roufosse F, Schandene L, Sibille C, Willard-Gallo K, Kennes B, Efira A, et al . Clonal Th2 lymphocytes in patients with the idiopathic hypereosinophilic syndrome. Br J Haematol 2000;109:540-8. |
| 7. | Thiele J, Zirbes TK, Kvancka HM, Fischer R. Focal lymphoid aggregates (nodules) in bone marrow biopsies: Differentiation between benign hyperplasia and malignant lymphoma - a practical guideline. J Clin Pathol 1999;52:294-300. |
| 8. | Metz J, McGrath KM, Savoia HF, Begley CG, Chetty R. T cell lymphoid aggregates in bone marrow in idiopathic hypereosinophilic syndrome. J Clin Pathol 1993;46:955-8. [PUBMED] [FULLTEXT] |
Correspondence Address:
Seema Sharma
Type IV/20, SGPGI Campus, Rae Bareli Road, Lucknow - 226 014, Uttar Pradesh
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0377-4929.42528
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