March 2014

A 1 day old male born at 38 weeks gestation

Dr. Okal, Dr. Bacaj, Dr. King, and Dr. Smolkin

Overview

The patient is a 1 day old male born at 38 weeks gestation to a 35 year old female via uncomplicated, spontaneous vaginal delivery with APGAR scores of 9 and 9 at one and five minutes, respectively. The mother had prenatal care that included standard screening for Hepatitis B surface antigen (negative), Rubella (immune), RPR (non-reactive), Group B Streptococcus (negative), Gonococcus (negative), and Chlamydia (negative). She also took prenatal supplements.

The infant was born with red-purple, blister-like, papulovesicular lesions with central pitting across the chest, abdomen, back, and extremities. Some lesions were firm and some were ulcerated. Minimal erythema surrounded the lesions. The infant was started on broad spectrum antibiotics and acyclovir for possible bacterial and viral causes while the workup for specific infections was pending. At presentation, laboratory studies did not reveal signs of possible systemic infection. A 4mm punch biopsy was also performed for histopathologic evaluation and tissue culture. Dermatologyic differential diagnosis included hemangiomatosis, congenital Langerhans cell histiocytosis, neonatal neuroblastoma, congenital leukemia cutis, as well as an infectious etiology including, but not limited to, TORCH infections such as toxoplasmosis, cytomegalovirus, and herpes simplex virus.

Gross Description

Sections of the skin punch biopsy show unremarkable squamous epithelium with a hypercellular dermal population of cells with abundant eosinophilic cytoplasm (Image 1). Throughout the dermis, there are scattered eosinophils, extravasated red blood cells, and a focal area of necrosis (Image 1, 2 and 4). Mitoses are easily identified (Image 3). Immunohistochemical stains were performed to further characterize the dermal population (Images 5 and 6). Other stains performed were negative and include: CD3, CD20, CD30, and CD34.

Image 1 : 4mm skin punch biopsy. 10x objective
Image 2 : 4mm skin punch biopsy. 10x objective
Image 3 : 4mm skin punch biopsy. 40x objective
Image 4 : 4mm skin punch biopsy. 40x objective
Image 5 : 4mm skin punch biopsy. 20x objective. Immunohistochemical stain for CD1a
Image 6 : 4mm skin punch biopsy. 10x objective. Immunohistochemical stain for S-100

Diagnosis

Based on the clinical summary, microscopic evaluation, and immunohistochemical staining profile, what is the most likely diagnosis ?

Answer

Please select an answer above.

Discussion

Langerhans cell histiocytosis (LCH) is a rare disorder characterized by a proliferation of CD1a positive Langerhans cells most commonly seen in children; however, it can be seen in any age group. 

Grossly, skin the lesions tend to be red/brown to blue papules. The most commonly seen skin sites of involvement include the scalp and trunk. The proliferations of Langerhan cells can be seen in internal organs including the lung, bone marrow, spleen, and liver. If the internal organs are involved, it is indicative of a worse prognosis and can be fatal. 
Microscopically, the epidermis tends to be partially ulcerated and can have some intraepidermal Langerhan cells (epidermotropism). The distribution of the Langerhan cells within the dermis may be lichenoid or diffuse. The dermis commonly has a mixed infiltrate of lymphocytes, eosinophils, neutrophils, and plasma cells. Extravasation of red blood cells is often seen. The Langerhan cells are 10-15 microns in diameter and contain abundant, pale, pink cytoplasm that can be foamy in appearence. If electron microscopy were preformed, the cytoplasm would contain tennis racket shaped, Birbeck granules. The nuclei can be irregular with a kidney-shape, folds/grooves, and/or inconspicuous nucleoli. The cells specifically stain with CD1a.  In addition, S-100, CD207 (langerin), and CD68 would be positive. CD207 is less commonly used but is highly sensitive and specific to Langerhans cells and is associated with the formation of the cytoplasmic Birbeck granules.

LCH presents clinically as several different disease syndromes of varying severity. Historically, each syndrome has been given a separate name: eosinophilic granuloma, Langerhans cell granulomatosis, histiocytosis X, Letterer-Siwe disease, Hand-Schuller-Christian disease, and Hashimoto-Pritzker disease. The latter three diseases refer to previously used names for clinical presentations of decreasing severity. Letterer-Siwe disease represents the most aggressive childhood form involving multiorgan involvement and can be fatal. Hand-Schuller-Christian disease represents a more indolent form with less widespread involvement seen in older children and adults. Hashimoto-Pritzker disease is a self-limited, congenital form. These were all later classified together under the name histiocytosis X, and later the X was identified to be Langerhans cells giving rise to the name LCH. Current recommendations suggest staging the disease based on bone, lymph node, skin, or multisystem involvement. The treatment is based on the extent of involvement ranging from self-limited to multisystem involvement requiring chemotherapy.

References

  1. Rosai, J. (2011). Rosai and ackerman's surgical pathology. (10th ed., Vol. 2, pp. 1803-4). New York, NY: Elseier, Inc.
  2. Rapini, R. (2012). Practical dermatopathology. (2nd ed., pp. 349-51). New York, NY: Elseier, Inc.