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Journal of Hematology

Case Report

Volume 3, Number 4, December 2014, pages 107-111

A Case of Langerhans Cell Histiocytosis With Risk Organ Involvement in a Young Adult

Langerhans cell histiocytosis (LCH) is a rare disease characterized by the proliferation and accumulation of dendritic cells, leading to organ dysfunction. It is most often diagnosed in childhood, but can occur at any age [1]. Morphologically, LCH cells stain positive for CD1a and/or CD207 (Langerin). Any organ/organ system can be affected; however, the most frequently affected include the skeleton, skin, pituitary, liver, spleen, hematopoietic system, lungs, lymph nodes and central nervous system (CNS) [2]. LCH is classified as either single system (SS-LCH) where one organ or system is involved, or multisystem (MS-LCH) where two or more systems are involved and may include “risk organs” (hematopoietic system, spleen and/or liver) [3]. Patients with SS-LCH are usually treated with local therapy, whereas MS-LCH requires systemic chemotherapy. Given the rarity of the disease, there is no clear standard of care, particularly data addressing the management of patients that fall within the relapsed population. There is even less data addressing patients that fall within the adolescent young adult (AYA) age group. We highlight an effective approach in such a patient.

A 33-year-old male presented with abdominal pain and anemia with a hemoglobin of 9.6 g/dL. CT scans revealed diffuse lymphadenopathy, bilateral hydroureteronephrosis, attributed to retroperitoneal fibrosis and an infiltrative process around the tail of the pancreas, aorta, and kidney. Soon after, the patient was intubated for hypercapneic respiratory failure. An infectious workup was negative. An axillary lymph node biopsy revealed CD1a positive histiocytes, consistent with LCH (Fig. 1).

Figure 1. Axillary lymph node biopsy with Langerhans cell histiocytosis. A (× 100, hematoxylin and eosin). The lymph node shows paracortical and sinus Langerhans cells that spare the follicles; B. (× 400, hematoxylin and eosin): The Langerhans cells show irregularly grooved and folded nuclei. Admixed lymphocytes, eosinophils, plasma cells, and multinucleated giant cells are present; C. (× 200, CD1a): The LCH cells are strongly CD1a positive; D. (× 200, S100): The LCH cells are strongly S100 positive. LCH: Langerhans cell histiocytosis; CD 1a: cluster of differentiation 1a.

Staging revealed “risk organ” involvement: the patient had a transaminitis suggesting liver involvement, and splenomegaly. His bone marrow biopsy was negative for disease. He also had hypernatremia consistent with diabetes insipidus managed with DDAVP; an MRI of the brain incidentally showed hyperdense lesions around the optic nerves suggestive of LCH involvement (Fig. 2).

Figure 2. MRI of the brain demonstrated hyperdense lesions around the optic nerves, lesions appearing hypointense to the cerebral cortex on T2-weighted imaging, suggestive of Langerhans cell involvement.

Therapy with prednisolone 125 mg daily and vinblastine weekly was initiated with resolution of respiratory failure within 1 week. Upon completion of this induction course, restaging scans demonstrated increasing axillary and inguinal adenopathy. B-RAF mutational analysis was negative. The patient was salvaged with cladribine and cytarabine for four cycles. Despite a 20% reduction in dose (given concern for toxicity), the patient’s course was complicated by prolonged cytopenias and sepsis. Restaging post-completion of therapy showed decrease of the soft tissue masses encasing the optic nerves, resolution of lymphadenopathy and stable mild splenomegaly. Surveillance scans 12 months later continue to demonstrate stability.

The majority of frontline studies for MS-LCH have been directed at the pediatric population (Table 1) [4-7]. The Histiocyte Society conducted three study protocols (LCH-I, II, and III), the results collectively establishing vinblastine and prednisolone for 6 weeks in children as the current standard of therapy [1]. Conversely, in the adult population, there is no clear standard of treatment and most studies are limited by small sample size with some suggesting that vinblastine/prednisolone ± 6-mercaptopurine (6MCP) can be applied to the adult population with good response (Table 1) [8-14].

In pediatric patients with refractory or relapsed MS-LCH, various therapeutic trials have been conducted as summarized in Table 2 [15-22]. Single agent cladribine has been studied with limited efficacy in patients with “risk organ” involvement [16, 17]. The combination of cladribine and cytarabine appears to achieve higher response rates with improved survival and low risk of reactivation [18, 19], serving as the basis for our treatment recommendations in our patient. More recently, higher survival rates have been demonstrated with clofarabine in cladribine refractory LCH [22].

Literature addressing the management of refractory/relapsed MS-LCH in adults is much less robust, most consisting of case reports (Table 2) [12, 23-27]. More recently, B-RAF mutations have been observed in 38% to 69% of cases of LCH [27], making salvage with vemurafenib an appropriate choice in patients that harbor the mutation.

The current case report not only stresses the variability in the management of MS-LCH in pediatric and adult populations alike but also highlights another therapeutic challenge - whether patients in the AYA group should be treated with a pediatric or adult regimen. The frontline use vinblastine/prednisolone ± 6MCP (if “risk organs” are involved) appears reasonable in both children and adults [4-6, 8-10]. However, when faced with refractory/relapsed disease, there is no consensus on how to treat the AYA group. We demonstrate that the combination of cladribine and cytarabine, typically used in children, can in fact be effective in B-RAF negative AYA patients. That being said, toxicity with this regimen is significant supporting the need for further assessment of better tolerated and more effective therapies.

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Journal of Hematology is published by Elmer Press Inc.