|Year : 2014 | Volume
| Issue : 4 | Page : 180-183
A rare clinical presentation of non-Hodgkins lymphoma as autoimmune haemolytic anaemia
Pradeep L Kumar1, E Avanthi2, KM Mahsheena3, Ira Bharadwaj3
1 Department of Pathology, Gadag Institute of Medical Sciences, Gadag, India
2 Jagadguru Jayadeva Murugarajendra Medical College, Davanagere, Karnataka, India
3 Department of Pathology, Karuna Medical College, Palakkad, Kerala, India
|Date of Web Publication||13-Oct-2014|
Pradeep L Kumar
S/O Lalya Naik, Purale, Manjunatha Nagar, Holebenavalli Post, Shimoga - 577 222, Karnataka
An elderly male patient presented with fever and easy fatigability. On examination, no significant clinical findings were noted except for solitary cervical lymph node and hypopigmented patches over the trunk. On serial lab investigation, haemoglobin was found to be rapidly decreasing. Direct Coombs test was positive and diagnosed as autoimmune haemolytic anaemia (AIHA). Peripheral smear showed leukoerythroblastic blood picture. Skin and lymph node biopsy showed features suggestive of non-Hodgkins lymphoma (NHL). Herein, we present a rare clinical presentation of NHL as AIHA.
Keywords: Autoimmune haemolytic anaemia, non-hodgkins lymphoma, angioimmunoblastic T-cell lymphoma
|How to cite this article:|
Kumar PL, Avanthi E, Mahsheena K M, Bharadwaj I. A rare clinical presentation of non-Hodgkins lymphoma as autoimmune haemolytic anaemia. J Health Spec 2014;2:180-3
|How to cite this URL:|
Kumar PL, Avanthi E, Mahsheena K M, Bharadwaj I. A rare clinical presentation of non-Hodgkins lymphoma as autoimmune haemolytic anaemia. J Health Spec [serial online] 2014 [cited 2020 Oct 30];2:180-3. Available from: https://www.thejhs.org/text.asp?2014/2/4/180/142791
| Introduction|| |
Non-Hodgkins lymphomas (NHLs) are more common among the elderly and predominately in men rather than females.  Two-thirds of NHLs present as enlarged lymph nodes (often >2 cm). The remaining one-third of NHLs present with symptoms related to the involvement of extranodal sites (eg: skin, stomach or brain).  There are many different types of NHL which can be divided into aggressive (fast-growing) or indolent (slow-growing) types that can be either from B-cells or T-cells. ,
The course of some autoimmune conditions are complicated by the development of NHL. Many explanations for the development of NHL has been suggested including chronic immune stimulation in autoimmune disease, the treatment for autoimmune diseases as well as shared genetic/environmental factors.  Autoimmune haemolytic anaemia (AIHA) may be a paraneoplastic syndrome in lymphoproliferative malignancies. 
The association between AIHA and NHL is well known and has been described in both B-cell and T-cell NHL. Pathogenesis of AIHA or all autoimmune phenomena complicating the course of NHL remains to be a matter of considerable controversy. ,,,,
| Case Report|| |
A 60-year-old male patient presented with low grade fever and easy fatiguability. On examination, no significant clinical findings were noted except for solitary cervical lymph node and hypopigmented patches over the trunk. On serial lab investigation, haemoglobin was found to be rapidly decreasing from 12.3 to 7.3 to 5 and later on to 4 gm%. Direct Coombs test was positive and diagnosed as autoimmune haemolytic anaemia. Peripheral smear showed leukoerythroblastic blood picture. Bone marrow was done to rule out infiltrative lesions and showed few clusters of atypical cells. However, since the patient's condition was deteriorating, lymph node and skin biopsy were done.
Sections from lymph node tissue revealed complete effacement of architecture by malignant lymphocytes. Cells were arranged in a diffuse pattern with condensed chromatin interspersed prolymphocytes. Malignant lymphocytes were observed obliterating the follicles and sinuses with infiltration through the capsule into surrounding adipose tissue which are features suggestive of NHL [Figure 1] and [Figure 2].
|Figure 1: Photomicrography of lymph node biopsy with features of NHL (H&E, 100×)|
Click here to view
|Figure 2: Photomicrography of lymph node biopsy with features of NHL (H&E, 400×)|
Click here to view
Sections from skin biopsy revealed epidermis with irregular acanthosis. Dermis showed nodular aggregates of atypical lymphocytes characterised by irregular nuclear margin with nuclear cleaving at few foci. Tumour cells were arranged around blood vessels with invasion into vessel wall. Features were suggestive of lymphoproliferative lesion (NHL). Immunohistochemistry (IHC) was suggested for confirmation and further subtyping; the reports were as follows: [Figure 3].
CD-3 (T-cell marker) - Positive.
Ki-67 (Proliferation marker) - 40-45%.
CD-23 (CLL/SLL marker) - Expanded follicular dendritic cells meshwork.
CD-4 (Helper T-cell marker) - Positive.
CD-20 (B-cell marker) - Negative.
CD-8 (Cytotoxic T-cell marker) - Negative.
Based on the above reports, a final diagnosis of angioimmunoblastic T-cell lymphoma was made.
| Discussion|| |
Numerous similarities are seen in the aetiology and pathogenesis of autoimmune diseases and malignant lymphomas. Though little is known about the occurrence of autoimmune features within lymphoma patients, patients with autoimmune disorders have increased risk to develop NHL. 
An increased risk of NHL was found in five non-systemic autoimmune conditions - AIHA, Hashimotos thyroiditis, Crohn's disease, Psoriasis and Sarcoidosis.  The impact of AIHA as an isolated phenomenon on the survival of patients with NHL has not been studied.  Multiple event process leads to the formation of auto antibodies in patients with B- or T-cell NHL. Immune tolerance mechanisms or failure to eliminate immature lymphocytes have been exposed to certain antigenic determinants on the surface of RBCs and platelets. Selected clones of auto reactive lymphocytes are generated by clotting factors or other cells and molecules. These cells may either be deleted from the immature repertoire through intact apoptotic mechanisms or remain reactive because of new genetic abnormalities (BCL-2, c-myc and others) or systemic dormant virus in the peripheral lymphoid compartment. Subsequently, the auto reactive clone infections are due to yet unknown events. 
Increased occurrence of autoimmune phenomena including AIHA in T-cell derived NHL has been described by other investigators. Significantly, lower survival of patients with NHL/AIHA was found in the study conducted by Sallah et al. 
Skin metastases occur in up to 9.1% of patients who have NHL.  The mechanism of cutaneous spread of disease most commonly involves retrograde lymphatic spread distal to the involved lymph nodes. In addition, direct extension from an underlying lymph node and haematogenous dissemination can be seen. The trunk is the most common site of involvement. The clinical presentation of NHL is firm, raised, smooth, slightly violaceous to erythematous nodules or plaques that range in size from few millimetres to a few centimeters. The nodules may breakdown producing ulcers with sharp borders. , Lymphoma of skin may look like a gumma of syphilis, as it is an indurated plaque called 'lymphoma en cuirasse' or erythema nodosum like subcutaneous nodules. Lymphoma cutis has also been reported to resemble a penile chancre.  Cutaneous T-cell lymphoma (CTCL) is more likely to be the underlying cause, although other lymphoreticular disorders are also rarely associated. In patients who have CTCL, erythroderma may be considered more of a direct result of tumour invasion rather than a paraneoplastic phenomenon. 
Angioimmunoblastic T-cell lymphoma is a peripheral T-cell lymphoma characterised by systemic disease. A polymorphous lymphoid infiltrate in lymph nodes and a prominent proliferation of high endothelial venules and follicular dendritic cells  . Immunohistochemistry can be performed on formalin fixed, paraffin-embedded tissue for the determination of the lineage and stage of maturation. Antigen markers useful in delineating and sub classifying lymphoid malignancies are the following:
- Primarily B-cell associated-CD19, CD20, CD79a.
- Mature B-cell lymphomas-CD5, CD10, CD11c, CD23, CD38, CD43, BCL6, BCL2, CyclinD1, CD138.
- Markers of Clonality- λ & k immunoglobin light chains.
- Primarily T-cell & NK cell associated- CD1, CD2, CD3, CD5, CD7, CD8, CD16, CD56, TIA-1, Granzyme B & perforin.
- Angioimmunoblastic T-cell lymphoma- CD2, CD3, CD4 with co-expression of CD10, follicular dendritic cells are highlightened by CD21, CD23, CD35, immunoblasts are CD20+ and EBV+. 
| Conclusion|| |
Although AIHA is a rare presentation in NHL, it should be considered as one of the important differential diagnosis in AIHA.
| Acknowledgements|| |
All staff and management of Karuna Medical College, Palakkad.
| References|| |
|1.||Longo DL. Malignancies of lymphoid cells. In: Fauci AS, Kasper DL, Longo DL, Braunwald E, Hauser SL, Jameson JL, editors. Harrison's Principles of Internal Medicine. 17 th ed. USA: McGraw-Hill Organization; 2008. p. 692-3. |
|2.||Kumar V, Abbas AK, Fauster N, Aster JC. Diseases of WBC, lymph nodes, spleen and thymus. In: Robbins and Cotran Pathologic Basis of disease. 8 th ed. Philadelphia: Elsevier Limited; 2010. p. 598-9. |
|3.||Chan JK. Tumors of the lymphoreticular system. In: Fletcher CD, editor. Diagnostic Histopathology of Tumors. 3 rd ed. Philadelphia: Elsevier Limited; 2007. p. 1219-21. |
|4.||Rosai J. Lymph node. In: Rosai and Ackerman's Surgical Pathology. 9 th ed. New Delhi: Elsevier Limited; 2005. p. 1931-3. |
|5.||Smedby KE, Baecklund E, Askling J. Malignant lymphomas in autoimmunity and inflammation: A review of risks, risk factors, and lymphoma characteristics. Cancer Epidemiol Biomarkers Prev 2006;15:2069-77. |
|6.||Ehrenfeld M, Abu-Shakra M, Buskila D, Shoenfeld Y. The dual association between lymphoma and autoimmunity. Blood Cells Mol Dis 2001;27:750-6. |
|7.||Sallah S, Gagnon GA. Angioimmunoblastic lymphadenopathy with dysproteinemia: Emphasis on pathogenesis and treatment. Acta Haematol 1998;99:57-64. |
|8.||Friedman DF, Cho EA, Goldman J, Carmacke CE, Besa EC, Hardy RR, et al. The role of clonal selection in the pathogenesis of an autoreactive human B-cell lymphoma. J Exp Med 1991;174:525-37. |
|9.||Mayer R, Logtenberg T, Stauchen J, Dimitriu-Bona A, Mayer L, Mechanic S, et al. CD5 and immunoglobulin V gene expression in B-cell lymphomas and chronic lymphocytic leukemia. Blood 1990;75:1518-24. |
|10.||Stevenson FK, Smith GJ, North J, Hamblin TJ, Glennie MJ. Identification of normal B-cell counterparts of neoplastic cells which secrete cold agglutinins of anti-1 and anti-I specificity. Br J Haematol 1989;72:9-15. |
|11.||Inghirami G, Foitl DR, Sabichi A, Zhu BY, Knowles DM. Autoantibody-associated cross-reactive idiotype-beanng human B lymphocytes: Distribution and characterization including IgV gene and CD5 antigen expression. Blood 1991; 78:1503-15. |
|12.||Zintzaras E, Voulgarelis M, Moutsopoulos HM. The risk of lymphoma development in autoimmune diseases: A meta-analysis. Arch Intern Med 2005;165:2337-44. |
|13.||Smedby KE, Hjalgrim H, Askling J, Chang ET, Gregersen H, Porwit-MacDonald A, et al. Autoimmune and chronic inflammatory disorders and risk of non-hodgkin lymphoma by subtype. J Natl Cancer Inst 2006;98:51-60. |
|14.||Sallah S, Sigounas G, Vos P, Wan JY, Nguyen NP. Autoimmune hemolytic anemia in patients with non-Hodgkin's lymphoma: Characteristics and significance. Ann Oncol 2000;11:1571-7. |
|15.||Coiffler B, Berger F, Bryon PA, Magaud JP. T-cell lymphomas: Immunologic, histologic, clinical and therapeutic analysis of 63 cases. J Clin Oncol 1988;6:1584-9. |
|16.||Horning SJ, Weiss LM, Crabtree GS, Wamke RA. Clinical and phenotypic diversity of T-cell lymphomas. Blood 1986; 67:1578-82. |
|17.||Schwartz RA. Cutaneous metastatic disease. J Am Acad Dermatol 1995;33:161-82. |
|18.||Smoller B. Other lymphopriliferative and myeloproliferative diseases. In: Bolognia JL, editor. Dermatology. 1 st ed., Vol. 2. Philadelphia: Elsevier's Health Sciences; 2003. p. 1943-51. |
|19.||Kurzrock R, Cohen PR. Mucocutaneous paraneoplastic manifestations of hematological malignancies. Am J Med 1995;99:207-16. |
|20.||Hassan A, Kreisel F. Lymph nodes. In: Humphrey PA, Dehner LP, Pfeifer JD, editors. The Washinton Manual of Surgical Pathology. 32 nd ed. New Delhi: Wolters Kluwer Pvt Ltd; 2008. p. 557-64. |
[Figure 1], [Figure 2], [Figure 3]