Indian Journal of Rheumatology

: 2021  |  Volume : 16  |  Issue : 1  |  Page : 89--92

A case of juvenile lupus with an extremely rare dendritic cell malignancy: Interdigitating dendritic cell sarcoma – coexistence or paraneoplastic manifestation?

Pratyusha Rajavarapu1, Deepika Ponnuru1, Megha Uppin2, Meher Lakshmi Konatam3, D Phani Kumar1, Liza Rajasekhar1,  
1 Department of Clinical Immunology and Rheumatology, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
2 Department of Pathology, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
3 Department of Medical Oncology, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India

Correspondence Address:
Dr. Pratyusha Rajavarapu
Flat Number 303, Sai Mitra Legacy, Kamalapuri Colony Phase II, Srinagar Colony, Hyderabad - 500 073, Telangana


Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease, characterized by circulating autoantibodies, widespread inflammation, and tissue destruction. The association between cancer and SLE is intriguing in view of their common pathophysiological pathways. It is established that there is an increased risk for overall malignancies in SLE, with standardized incidence ratios ranging from 1.14 to 3.6. Hematological malignancies are more common than solid organ malignancies in SLE. Malignancy when associated with lupus usually follows the diagnosis, but can occur concurrently or even predate the diagnosis of SLE. Neoplasms of dendritic cells (DCs), the key antigen-presenting cells, are rare, and they account for <1% of all lymph node tumors. Interdigitating DC sarcoma (IDCS) is a rare hematological malignancy of DCs, with only a few over 100 cases being reported in literature. IDCS is usually seen in elderly males in their sixth decade. Here, we report a rare case of SLE and IDCS occurring together in a 5-year-old girl. The persistence of lymphadenopathy despite improvement in other lupus-specific features following the initiation of treatment led to a suspicion of malignancy which was proven on histopathology. Another unique feature of our case was that remission and relapse of both SLE and IDCS occurred synchronously. Although this presentation is rare, clinicians must be aware of the possibility of SLE and malignancies occurring together, especially in the presence of atypical clinical manifestations such as persistent lymphadenopathy. This knowledge helps in early diagnosis and effective treatment of both these conditions.

How to cite this article:
Rajavarapu P, Ponnuru D, Uppin M, Konatam ML, Kumar D P, Rajasekhar L. A case of juvenile lupus with an extremely rare dendritic cell malignancy: Interdigitating dendritic cell sarcoma – coexistence or paraneoplastic manifestation?.Indian J Rheumatol 2021;16:89-92

How to cite this URL:
Rajavarapu P, Ponnuru D, Uppin M, Konatam ML, Kumar D P, Rajasekhar L. A case of juvenile lupus with an extremely rare dendritic cell malignancy: Interdigitating dendritic cell sarcoma – coexistence or paraneoplastic manifestation?. Indian J Rheumatol [serial online] 2021 [cited 2022 Jan 24 ];16:89-92
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Systemic lupus erythematosus (SLE) is a multisystem, autoimmune disease predominantly affecting young women. Many studies documented increased risk of malignancy, especially hematological in SLE.[1] Neoplasms of dendritic cells (DCs), the key antigen-presenting cells, are rare, and they account for <1% of all lymph node tumors. Among them, interdigitating DC sarcoma (IDCS) is a less common subtype and its diagnosis is based on immunohistochemistry (IHC) studies.[2] Its association with SLE has not been previously reported.

 Case Report

A 5-year-old girl presented with a 3½-month history of high-grade intermittent fever and erythematous maculopapular rashes over both the upper and lower limbs [Figure 1], following which she developed inflammatory arthritis involving both knees and ankles. On examination, she had significant bilateral cervical, axillary, and inguinal lymphadenopathy and mild hepatosplenomegaly. Initial lymph node biopsy was suggestive of reactive follicular hyperplasia without evidence of malignancy. Blood investigations revealed positive anti-nuclear autoantibody (ANA) on immunofluorescence with 4+ (Speckled) pattern in a dilution of 1:100, dsDNA positive (2.1 [Systemic lupus erythematosus and malignancy

In addition to renal injury and infection, malignancy is known to be a significant cause of death in SLE. Lupus patients have a slightly higher overall malignancy risk with standardized incidence ratios (SIRs) of 1.14–3.6. This risk could be explained by the common immune and genetic pathways underlying the pathogenesis of SLE and malignancy.[1] Autoantibodies seen in SLE can alter DNA repair and lead to the accumulation of DNA damage, which increases the risk of cancer. Examples of such antibodies include anti3E10.[3] Anticardiolipin antibodies were also a risk factor for malignancy.[4] The cytokines, BAFF, and APRIL, responsible for the survival and proliferation of B cells, are overexpressed in both SLE and non-Hodgkin lymphoma (NHL) (particularly diffuse large B-cell lymphoma [DLBCL]). These cytokines can cause overstimulation and aberrant activation of B cells culminating in mutagenesis.[5] Further, immunosuppressant drugs (ISDs) may mediate the development of malignancy by causing alteration in the immune cells through mutagenesis and cytotoxicity. ISDs can also result in decreased clearance or increased susceptibility to oncogenic viruses, especially human papillomavirus. Owing to the fact that patients who are on higher immunosuppressive treatment also have higher disease activity, it is difficult to establish the exact etiological role of ISDs in cancer development.[1],[6]

Hematological malignancies, particularly lymphomas, are more commonly associated with lupus than solid organ malignancies. In a meta-analysis by Apor et al.,[7] including 67,929 patients from eight cohort studies, there was 2.9-fold increase (95% confidence interval [CI]: 2.0–4.4) in the incidence of all hematologic malignancies in lupus patients. In a meta-analysis, Cao et al.[8] demonstrated an increased incidence of NHL with pooled relative risks of 5.40 (95% CI: 3.75–7.77) (most common being DLBCL), 3.26 (95% CI: 2.17–4.88) for Hodgkin's lymphoma, and 2.01 (95% CI: 1.61–2.52) for leukemia.

Malignancy in juvenile SLE was less extensively studied. In a cohort study including data from 12 pediatric rheumatology clinics in North America, 1168 patients were followed up for 7.6 years (interquartile range 3.4–10). Among them, 14 invasive cancers occurred, producing an SIR of 4.13 (95% CI: 2.26–6.93). Of them, three were NHL; two were head-and-neck squamous cell carcinomas (tongue and nasopharynx); and one each of glioblastoma, thyroid papillary adenoma, breast cancer, and adenocarcinoma not otherwise specified; and three cancers whose morphology and histology codes were indeterminate.[9]

In a recent large meta-analysis of 96,578 patients from 25 adult case series and 5 pediatric case series comparing malignancy rates in adult- and childhood-onset SLE, cancer incidence was lower in childhood-onset SLE (0.5%, 95% CI: 0.03%–1.5%) versus adult-onset SLE (4.2%, 95% CI: 3.2%–5.3%). They found a bimodal pattern to the onset of hematologic malignancies in juvenile SLE, with younger children having a higher risk of leukemia and older children of lymphoma.[10] Most of the data show that malignancy is detected after the diagnosis and treatment of SLE. However, one study assessing the hematological malignancy incidence in SLE described that nearly one-third of the patients were diagnosed earlier or concurrently with a diagnosis of malignancy. Such patients were found to have a better outcome pertaining to malignancy.[11]

Another area of interest is SLE presenting as a paraneoplastic manifestation. Paraneoplastic symptoms are caused by a malignancy, but not directly related to invasion by the tumor or its metastases, and are the result of a wide variety of tumor-derived biologic mediators such as hormones, peptides, antibodies, cytotoxic lymphocytes, and autocrine and paracrine mediators. Inflammatory myopathies, seronegative rheumatoid arthritis, and atypical vasculitides are frequently reported paraneoplastic rheumatic diseases, and paraneoplastic lupus-like (pLE) syndromes are less common.[12] About 33 cases of pLE were reported till date, associated with solid organ malignancies such as lung, breast carcinoma, and hematological malignancies such as acute myeloid leukemia.[13] The most common presentations in pLE were subacute cutaneous lupus, serositis, Raynaud's phenomenon, and ANA and anti-dsDNA antibody positivity. Owing to the close temporal relation between the onset and flare of both lupus and IDCS, in this case, a differential of pLE could be considered. However, the complete clinical picture of SLE, particularly with hypocomplementemia and nephritis as seen here, is rare.

Interdigitating dendritic cell sarcoma: A brief review

Peripheral lymphoid organs contain a group of structural and immune accessory cells called reticulum cells. They constitute a minor fraction in these organs and encompass different types of DCs.[14] The following four types of DCs exist in lymph nodes: follicular DC (FDC), interdigitating DCs (IDCs), Langerhans, and histolytic/fibroblastic cells. FDCs are localized to the germinal center and present antigens to B cells, whereas IDCs are localized to the paracortex of lymph nodes and the periarteriolar lymphoid sheaths in the spleen and present antigens to T cells.[15] DC neoplasms are uncommon, and the WHO has classified them into the following five groups: Langerhans cell histiocytosis, Langerhans cell sarcoma, IDCS, FDC sarcoma, and not specified otherwise.[2]

Among them, FDC sarcoma is the most common type followed by IDCS. A recent pooled analysis of 462 cases of DC sarcomas showed that only 100 cases of IDCS were reported. It was the most aggressive form among all, and the median age at diagnosis was 56.5 (1.8–88) years with a male predominance (1.38:1). Painless lump in cervical or axillary areas was the most common presentation. Fever, weight loss, night sweats, and fatigue have been reported. Isolated nodal disease (47%) involving the cervical area was most common, followed by combined nodal and extranodal involvement (28%) and isolated extranodal disease (25%), with liver being the most common extranodal site involved. Patients with gastrointestinal involvement presented with intestinal obstruction, abdominal pain, or dyspepsia.[14]

Diagnosis of IDCS can be challenging because of its rarity and morphologic similarity to many of the spindle cell neoplasms involving lymph nodes. Microscopically, IDCS has large fusiform spindle cells with storiform or whorled growth pattern with small nucleoli resembling histiocytes. The presence of small lymphocytes intermingling with large histiocytic cell population is a key diagnostic feature of IDCS, which differentiates it from carcinomas, lymphomas, and sarcomas, which are the closest differentials histologically.[16] In IDCS, IHC plays a crucial role which is characterized by positive staining for S-100, vimentin, human leukocyte antigen-antigen D related or CD-68, and leukocyte common antigen and negative staining for CD1a, CD21, CD35, CD30, CD20, cytokeratin (CK), myeloperoxidase, and langerin.[15] In our case, staining for S-100 was positive, but CD1a, CD21, CD30, and Pan CK were negative, thus confirming the diagnosis.

The etiopathogenesis of IDCS is unknown. Epstein–Barr virus has been suggested as a causative factor in the development of FDC sarcomas, but not IDCS. However, the association of IDCS with preceding or concomitant malignant neoplasms has been suggested in case reports.[17] Saygin et al. reported concurrence rates of 12% with hematopoietic and up to 9% with solid organ malignancies, in patients with IDCS during their lifetime. This high frequency may be related to aging, or may support the hypothesis that DCs introduce tumor antigens to immune cells and that their dysfunction could result in a diminished response to the neoplasm.[14] Interestingly, there were three case reports of development of IDCS following topical and systemic therapy with calcinuerin inhibitors, given for eczema, seborrheic dermatitis, and following liver transplant. These drugs dampen the response of T cells to which IDCs present antigens. Thus, dysregulation of immune system may facilitate malignant transformation of IDCs, but further data are required to elucidate it.[18],[19]


We report a case of juvenile SLE coexistent with an extremely rare DC malignancy. IDCS occurred very early in the disease course and relapse of the malignancy was associated with flare of the disease. Although DCs were proven to have a role in the pathogenesis of development of lupus, no association between IDCS and lupus has been reported previously.

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 the child's name and initial will not be published, and due efforts will be made to conceal patient identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


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