Pediatric Anaplastic Large Cell Lymphoma Presenting as Generalized Lymphadenopathy

Pediatric Anaplastic Large Cell Lymphoma Presenting as Generalized Lymphadenopathy

ABSTRACT: Because a finding of generalized lymphadenopathy can be associated with such a wide range of diseases and conditions, determining its cause can sometimes be challenging. Infectious causes are the most common; however, it is important also to consider other entities in the workup. Here we present the case of a 3-year-old girl with generalized lymphadenopathy and fever, in whom the cause of the symptoms was initially thought to be infectious. Ultimately, however, anaplastic large cell lymphoma (ALCL) was diagnosed. Using this case as a backdrop, we discuss the wide range of systemic illnesses that the differential diagnosis of generalized lymphadenopathy encompasses—including infectious, autoimmune, and oncological disorders. We discuss the different findings typically seen in the various entities that figure prominently in the differential, and we outline investigations that can help narrow it. Finally, we present an overview of ALCL, one of the more rare pediatric malignancies.

Generalized lymphadenopathy is a common finding and has an extensive differential diagnosis. Because generalized lymphadenopathy often has an infectious origin, other less common causes, especially neoplastic causes, can easily be missed.

Here we report the case of a toddler who presented with inguinal lymphadenopathy and fever and in whom supraclavicular, cervical, and axillary lymphadenopathy developed several days later. Initially, bacterial lymphadenitis was diagnosed; however, an infectious disease workup revealed no evidence of either a bacterial or viral infection. Oncological causes were then investigated, and ultimately, anaplastic large cell lymphoma was diagnosed.

Case Report

A 3-year-old girl presented with a 10-day history of “swelling around her vagina” and difficulty walking for 3 days. Her mother had first noted this nontender swelling over the patient’s mons pubis region while bathing her, and on the day of presentation, two tender “bumps” had developed in the inguinal area. Over the past 2 weeks, she had had tactile fevers, night sweats, and fatigue. She also appeared to have lost weight. There was no known tuberculosis (TB) or animal exposure and no travel history.


The child had been well until 4 months earlier. At that time—and at another hospital—she received intravenous gammaglobulin for presumed Kawasaki disease (she had right cervical lymphadenopathy, an erythematous rash, and chapped lips). Her symptoms appeared to resolve with this therapy.

Three weeks before her latest visit, the patient had been admitted to yet another hospital for evaluation of refusal to walk; she underwent workup for a septic hip. Ultrasonography, MRI, and two joint aspirations showed no conclusive evidence of a joint infection. However, she was found to be anemic. She was treated with a 2-week regimen of clindamycin, and her symptoms improved.

Initial Evaluation

Her physical exam on admission was significant for warm, tender, firm inguinal masses bilaterally that measured approximately 6 cm on each side. She had no other masses, lymphadenopathy, or hepatosplenomegaly. Breath sounds at the left lung base were decreased. She could bear weight but was reluctant to move her hips because of pain.

The admission complete blood cell (CBC) count revealed the following values: hemoglobin, 9.2 g/dL; hematocrit, 30%; mean corpuscular volume, 61.9 fL; mean corpuscular hemoblobin, 19 pg; reticulocyte count, 1.3%; white blood cell count, 15,500/µL with 55% neutrophils, 43% lymphocytes, and 2% monocytes; and platelet count, 34,100/µL.

Hemoglobin electrophoresis revealed a normal AA pattern with normal quantitative hemoglobin A2 level (2.8%) and an elevated level of hemoglobin F (2.2%). Levels of electrolytes, liver enzymes, lactate dehydrogenase, and uric acid were within normal limits. Serum iron level and iron binding capacity were both low; serum ferritin level was normal. C-Reactive protein (CRP) level was elevated at 5.7 mg/dL; erythrocyte sedimentation rate (ESR) was 82 mm/hr.

Orthopedic consultation and ultrasound evaluation of her hips did not suggest a septic joint.

Anaplastic large cell lymphoma. In this patient, computed tomography (CT) of the chest (A) demonstrates a left pleural effusion and bilateral axillary lymphadenopathy measuring up to 7.6 cm. CT of the pelvis (B) demonstrates inguinal lymphadenopathy measuring up to 2.4 × 1.4 × 2 cm at the right groin.

Hospital Course

Initially, acute bacterial lymphadenitis was diagnosed. Intravenous antibiotics were started, and the patient’s inguinal adenopathy improved minimally. An infectious disease workup was initiated, including placement of a purified protein derivative (PPD) test, measurement of Epstein-Barr virus (EBV) and coccidioidomycosis titers, a rapid HIV antibody test, Bartonella serologies, and blood polymerase chain reaction (PCR) testing for cytomegalovirus (CMV).

On the third hospital day, the patient was noted to have new supraclavicular, cervical, and axillary lymphadenopathy. Concern for an oncological process prompted computed tomography (CT) imaging of the head, neck, chest, abdomen, and pelvis; the scan revealed a large left pleural effusion and left cervical, left supraclavicular, bilateral axillary, diffuse abdominal, and bilateral inguinal lymphadenopathy (Figure). On gallium scanning, the abnormal regions on the CT scan were gallium avid. Bilateral bone marrow aspirates and biopsies were negative for malignancy. Examination of the pleural fluid did not demonstrate any malignant cells. Her cerebrospinal fluid (CSF) was acellular, and cytology evaluation did not reveal any malignant cells. Results of a subsequent biopsy of the right inguinal lymph node were diagnostic of anaplastic large cell lymphoma (ALCL), lymphohistiocytic variant. This patient’s ALCL was anaplastic lymphoma kinase (ALK)–positive on immunohistochemical staining. However, neither cytogenetics nor fluorescence in situ hybridization demonstrated any translocations involving chromosome 2 (the location of the ALK gene) that might have accounted for the expression of the ALK protein.


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