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 Table of Contents  
Year : 2021  |  Volume : 14  |  Issue : 1  |  Page : 160-163

Histiocytic necrotizing lymphadenitis with systemic lupus erythematosus mimicking like lymphoma

1 Department of Laboratory Medicine, Yashoda Hospital, Hyderabad, Telangana, India
2 Department of Medicine, Yashoda Hospital, Hyderabad, Telangana, India
3 Department of Rheumatology, Yashoda Hospital, Hyderabad, Telangana, India
4 Department of Radiology, Yashoda Hospital, Hyderabad, Telangana, India

Date of Submission10-Aug-2020
Date of Acceptance15-Oct-2020
Date of Web Publication09-Feb-2021

Correspondence Address:
Dr. Majed Abdul Basit Momin
Department of Laboratory Medicine, Yashoda Hospital, Malakpet, Nalgonda x-roads, Hyderabad - 500 036, Telangana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/kleuhsj.kleuhsj_258_20

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Histiocytic necrotizing lymphadenitis (HNL) is a rare idiopathic disorder. It is frequently underdiagnosed due to its nonspecific clinical features, mimicking like lymphomas, autoimmune diseases, and infectious reactive lymphadenopathy. Histological examination of the lymph node is the basis of diagnosis in HNL. We report a 40-year-old male patient who presented with fever for 4 weeks. After an extensive workup, laboratory investigations revealed progressive pancytopenia, gradual increase in serum lactate dehydrogenase, and ferritin with negative pyrexia profile. His radiological imaging including positron emission tomography/computed tomography showed multiple intra-abdominal, cervical, and axillary lymphadenopathies. Finally, the histological section from axillary lymph node core biopsy revealed a diagnosis of HNL. Subsequent autoimmune workup met diagnostic criteria for systemic lupus erythematosus. This case report alerts the clinicians regarding this rare disease and emphasizes the important role of morpho-histopathology in early recognition of this rare entity.

Keywords: Histiocytic necrotizing lymphadenitis, histological examination, pancytopenia, systemic lupus erythematosus

How to cite this article:
Momin MA, Sarda AK, Kayidhi S, Ingle A, Borad DK. Histiocytic necrotizing lymphadenitis with systemic lupus erythematosus mimicking like lymphoma. Indian J Health Sci Biomed Res 2021;14:160-3

How to cite this URL:
Momin MA, Sarda AK, Kayidhi S, Ingle A, Borad DK. Histiocytic necrotizing lymphadenitis with systemic lupus erythematosus mimicking like lymphoma. Indian J Health Sci Biomed Res [serial online] 2021 [cited 2021 Apr 17];14:160-3. Available from: https://www.ijournalhs.org/text.asp?2021/14/1/160/308957

  Introduction Top

Histiocytic necrotizing lymphadenitis (HNL) is also known as  Kikuchi-Fujimoto disease More Details. HNL is a benign, self-limiting disease of unknown origin. It commonly affects young females under the age of 30 years. The most common clinical feature of HNL is prolonged fever with lymphadenopathy.[1] In developing countries, like India, fever with lymphadenopathy is traditionally associated with tuberculous etiology. The clinical features and radiological imaging findings of lymphoma and extrapulmonary tuberculosis could be quite similar. Hence, difficulty in diagnosis has been reported.[2]

The diagnosis of HNL solely depends on the histomorphological examination of lymph node, which typically reveals necrosis surrounded by histiocytes, crescentic nucleus, immunoblasts, plasma cells, and absence of neutrophils.[3] Although viral and autoimmune etiologies have been proposed for the pathogenesis of HNL, there is no convincing evidence linking HNL to either of these etiologies. An association of HNL, pancytopenia, and systemic lupus erythematosus (SLE) has been noted in a review of the literature.[4] The case described here is of a rare association of HNL with SLE, presenting with fever of prolonged duration and pancytopenia.

  Case Report Top

A 40-year-old male presented in our Yashoda Hospital, ER (emergency room) department with a history of prolonged fever for 4 weeks, cough, nausea, and generalized weakness for 2 weeks. There was no history of rashes, joint pains, excess hair loss, oral ulcers, night sweats, or weight loss. His vital parameters showed a temperature of 101°F and a pulse rate of 98 beats/min with normal respiratory rate and blood pressure. On general examination, there was no pallor or icterus. Bilateral cervical lymph nodes and right axillary deep-seated lymph nodes were palpable. Mild splenomegaly was observed on per abdominal examination.

Initial laboratory investigations [Table 1] including hematological findings showed pancytopenia with an erythrocyte sedimentation rate (ESR) of 30 at the end of 1 h. Reticulocyte count, malarial antigen detection test, direct and indirect Coombs tests, coagulation test including prothrombin time, activated partial thromboplastin time, and fibrinogen were with in normal limits. Routine urine examination was normal. Serological examination for typhoid, scrub typhus, leptospirosis, Weil–Felix test,  Brucella More Details IgM, and dengue IgM/IgG were negative. Viral serology was nonreactive for human immunodeficiency virus (HIV), HBsAg, and hepatitis C virus. The result of the patient's Mantoux test was negative. Biochemical investigation revealed a mild increase in liver aminotransferase level with increased levels of serum lactate dehydrogenase (LDH) and serum ferritin. Renal function tests were normal.
Table 1: Laboratory data

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Radiological examination for chest X-ray showed a normal study. An ultrasound abdomen scan showed mild splenomegaly (130 mm), whereas a cervical (neck) scan showed bilateral cervical lymphadenopathy and right-sided, deep-seated axillary lymph node with loss of fatty hilum. Further, a positron emission tomography/computed tomography (PET-CT) was ordered to determine the size and extent of the lymphadenopathy. PET-CT scan whole body showed hypermetabolic, multiple, enlarged supra- and infradiaphragmatic lymph nodes suggestive of lymphoproliferative disorder. Based on radiological and laboratory findings, a provisional diagnosis of lymphoma with secondary hemophagocytic lymphohistiocytosis (HLH) was made. Axillary lymph node core biopsy and bone marrow aspiration examination were performed to confirm the diagnosis. Bone marrow aspiration cytology revealed a reactive cellular marrow with normal trilineage hematopoiesis with no evidence of hemophagocytosis or marrow infiltration.

Right-sided axillary lymph node core biopsy sections show [Figure 1] mature lymphoid cells and areas of necrosis with numerous nuclear debris. Histiocytic proliferation engulfing nuclear debris and some crescentic nuclei were also seen. There was no evidence of granulomas, and stain for acid-fast bacillus was noncontributory. The overall histological features favored a diagnosis of HNL, and further autoimmune workup was suggested. The autoimmune workup revealed positive antinuclear antibodies with high titer (1:1000) and homogeneous nucleocytoplasmic fluorescence pattern. Serological examination of Antinuclear antibody profile showed strong positivity for Ro-52, SS-A, SS-B and negative for anti-double-stranded DNA antibodies, anti-smith, and anti-ribonucleic proteins. Complement proteins C3 and C4 were within normal limits. A final diagnosis of HNL with SLE and pancytopenia was made and treated with steroids and supportive management. Clinical condition improved, and the patient was afebrile after 2 days of initiation of treatment. Progressive improvement was seen in serum LDH and serum ferritin levels, with complete improvement seen in hematological parameters on day 14 [Table 1]. An ultrasound and CT scan after 2 weeks revealed a complete resolution of cervical, axillary, and abdominal lymph nodes. The dose of steroids was tapered slowly after a month, and the patient is doing well now.
Figure 1: Histological examination of axillary lymph node core biopsy. Right axillary lymph node histological section microscopy (H and E stained) (a and b) (×10) view showing large areas of necrosis, (×40) nuclear debris (blue arrow) (c) necrosis (d) crescentic nucleus (blue arrow) and histiocytes engulfing nuclear debris (green

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  Discussion Top

HNL was first described by pathologists Kikuchi and Fujimoto in the year 1972. The disease mainly affects women, in their third to fourth decade of life, with a male-to-female ratio of 1:4, and its prevalence is higher among the Asian population.[3] The etiology of HNL is still unknown, and speculations exist regarding its relationships with previous viral infections such as Epstein–Barr virus, HIV, dengue virus, parvovirus B19, human T-lymphotropic virus 1, and autoimmune conditions. However, the histopathological features of these lymphadenitis diseases differ from those of HNL, and in many cases, no infectious agent is found.[5] The other implicated etiology is an autoimmune disease, particularly SLE, but no studies have confirmed any positive serological findings related to antinuclear antibodies and rheumatoid factors. Recent proposed studies have demonstrated that after viral infection, activated cytotoxic T-cells in the lymph nodes induce apoptosis of CD4+ lymphocytes. Apoptotic lymphocytes can deliver nuclear antigens and trigger autoimmune T- and B-cells to produce antinuclear antibodies.[6]

The clinical pattern of presentation is fever and lymphadenopathy, more commonly posterior cervical lymph nodes and jugular lymph nodes. Other less common symptoms are nausea, weakness, and arthralgia. The axillary, intraparotid, thoracic, mesenteric, intra-abdominal, and inguinal chains may also be involved.[7] Routine laboratory investigations usually do not aid in the diagnosis except leucopenia (25%–50%), high ESR (>60 mm at 1 h in 70% patients), and C-reactive protein. Atypical lymphocytes may be seen in peripheral blood in 25%–30% of cases. Fine-needle aspiration cytology (FNAC) from lymph nodes has a limited role in establishing the diagnosis of HNL. The diagnostic yield of FNAC is only 56%.[8] The radiological imaging techniques, such as an ultrasound, CT, magnetic resonance imaging, and PET-CT scanning, also rarely provide a conclusive diagnosis. An incorrect provisional diagnosis of lymphoma or extrapulmonary tuberculosis diagnosis is made in many instances.[9]

The reliable method of diagnosis is histomorphological examination of a lymph node excision biopsy. The histology shows patchy areas of necrosis including nuclear fragments surrounded by pale histiocytes. The cellular debris is actively phagocytosed by numerous histiocytic cells with abundant cytoplasm and peripherally compressed, crescentic nuclei resembling signet-ring cell. Neutrophils and eosinophils are consistently absent. The immunophenotype of Kikuchi disease is primarily composed of mature CD8-positive and CD4-positive T-lymphocytes. Positive immunostaining results by monoclonal antibody Ki-M1P are seen in Kikuchi disease but not in malignant lymphoma. The histological differential diagnoses are tuberculosis, lymphoma, sarcoidosis, SLE, infectious mononucleosis, and syphilis.[3] Among these, SLE presents the most difficult differential consideration, as sometimes, variable degrees of paracortical necrosis with karyorrhectic debris and histiocytic infiltrate are seen. SLE lymphadenitis often demonstrates hematoxylin bodies (aggregates of degenerated nuclear debris) and aggregates of degenerated nuclear material in the wall of blood vessels (Azzopardi phenomenon).[10]

Pancytopenia is often related to autoimmune conditions, HLH, macrophage activation syndrome, or sepsis. HLH causing pancytopenia has been previously described in cases of HNL.[11] However, in our case, there was no evidence of hemophagocytes or atypical lymphoid proliferation in bone marrow or in lymph node histology. The treatment of HNL is not well established and generally supportive. Nonsteroidal anti-inflammatory drugs can be used to alleviate fever and lymph node tenderness. The use of steroids has been recommended in severe forms of disease and extranodal involvement.[12] Intravenous immunoglobulins have also been tried with some success.[13]

  Conclusion Top

HNL is an uncommon disease which needs to be considered in workup for differential diagnoses of fever with lymphadenopathy. Morpho-histology of lymph node biopsy plays a crucial role in the diagnosis of this rare entity. The association of HNL with an underlying autoimmune disease like SLE must be ruled out for early treatment and to avoid morbidity and mortality related to it.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the legal guardian has given his consent for images and other clinical information to be reported in the journal. The guardian understands that names and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Kaur S, Mahajan R, Jain NP, Sood N, Chhabra S. Kikuchi's disease – A rare cause of lymphadenopathy and fever. J Assoc Physicians India 2014;62:54-7.  Back to cited text no. 1
Nayia P, Mathew J, Thomas EC. Unusual association of diseases/symptoms: A patient presenting with generalized lymphadenopathy-sarcoidosis, lymphoma or tuberculosis? BMJ Case Reports 2012;2012:bcr1120115150.  Back to cited text no. 2
Ioachim HL, Medeiros LJ. Kikuchi lymphadenopathy. In: Iochim HL, Medeiros LJ, editors. Ioachim's Lymph Node Pathology. 4th Ed. Philadelphia: Lippincott Williams & Wilkins; 2009. p. 199-202.  Back to cited text no. 3
Martinez-Vazquez C, Hughes G, Bordon J, Alonso-Alonso J, Anibarro-Garcia A, Redondo-Martinez E, et al. Histiocytic necrotizing lymphadenitis, Kikuchi-Fujimoto's disease, associated with systemic lupus erythematosus. QJM: Int J Med 1997;90:531-3.  Back to cited text no. 4
Bosch X, Guilabert A, Miquel R, Campo E. Enigmatic Kikuchi-Fujimoto disease: A comprehensive review. Am J Clin Pathol 2004;122:141-52.  Back to cited text no. 5
Alijotas-Reig J, Casellas-Caro M, Ferrer-Oliveras R, Cabero-Roura L, Vilardell-Tarres M. Recurrent Kikuchi-Fujimoto disease during pregnancy: Report of case evolving into systemic lupus erythematosus and review of published work. J Obstet Gynaecol Res 2008;34:595-8.  Back to cited text no. 6
Norris AH, Krasinskas AM, Salhany KE, Gluckman SJ. Kikuchi-Fujimoto disease: A benign cause of fever and lymphadenopathy. Am J Med 1996;101:401-5.  Back to cited text no. 7
Sousa Ade A, Soares JM, Sá Santos MH, Martins MP, Salles JM. Kikuchi-Fujimoto disease: Three case reports. Sao Paulo Med J 2010;128:232-5.  Back to cited text no. 8
Ito K, Morooka M, Kubota K. Kikuchi disease: 18FFDG positron emission tomography/computed tomography of lymph node uptake. Jpn J Radiol 2010;28:15-9.  Back to cited text no. 9
Mahajan T, Merriman RC, Stone MJ. Kikuchi-Fujimoto disease (histiocytic necrotizing lymphadenitis): Report of a case with other autoimmune manifestations. Proc (Bayl Univ Med Cent) 2007;20:149-51.  Back to cited text no. 10
Wano Y, Ebata K, Masaki Y, Takeshita S, Ogawa N, Kim CG, et al. Histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto's disease) accompanied by hemophagocytosis and salivary gland swelling in a patient with systemic lupus erythematosus. Rinsho Ketsueki 2000; 41:54-60.  Back to cited text no. 11
Jang YJ, Park KH, Seok HJ. Management of Kikuchi's disease using glucocorticoid. J Laryngol Otol 2000;114:709-1.  Back to cited text no. 12
Noursadeghi M, Aqel N, Gibson P, Pasvol G. Successful treatment of severe Kikuchi's disease with intravenous immunoglobulin. Rheumatology (Oxford) 2006;45:235-7.  Back to cited text no. 13


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  [Table 1]


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