Lananh Nguyen, M.D.Division of Neuropathology

University of Pittsburgh Medical Center

15-year-old boy presenting with back pain and skull lesion

• Patient complained of back pain. An MRI was done (not shown) which showed multiple osseous lesions in the spine and pelvis. A biopsy of the pelvis was called chronic osteomyelitis.

• On physical exam, a nontender growing skull lesion was seen.

• And, imaging was performed.

Clinical history

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Radiology: Identify the lesion and name the 3 imaging modalities used below.

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T1 T2 T1 with contrast

Radiology: Imaging of the skull lesion. Identify the lesion and name the 3 imaging modalities used below.

• Click on the hyperlink below to view the virtual slide– Intraoperative smear

• What do you see on the smear?

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A biopsy was performed and an intraoperative consultation was requested.

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A biopsy was performed and an intraoperative consultation was requested. What do you see on the smear?

Low power

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Giant cells

Numerous macrophages

A biopsy was performed and an intraoperative consultation was requested. What do you see on the smear?

Low power

This is the same smear at higher power. What do you see?

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High power

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High power

Nuclear indentation

Nuclear groove

This is the same smear at higher power. What do you see?

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This is what the H&E permanent slides look like.

• Click on the hyperlink below to view the virtual slide– Permanent H&E slide

• What do you see on the slide?

This is what the H&E permanent slides look like.

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What is your diagnosis?

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We’re not telling the diagnosis yet. What immunohistochemical stains would you like to do?

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• These were ordered– S100– CD68 PGM– CD1a– Langerin– CD163

• What is in the differential based on this panel?

What immunohistochemical stains would you like to do?

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Immunostain Langerhan Cell Histiocytosis

Juvenile Xanthogranuloma

Reactive histiocytes

S100

CD68 PGM

CD1a

Langerin

CD163

Fill in the panel by denoting “+” or “–”

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Immunostain Langerhan Cell Histiocytosis

Juvenile Xanthogranuloma

Reactive histiocytes

S100 + - +/-

CD68 PGM - + +

CD1a + - -

Langerin + - -

CD163 - + +

Fill in the panel by denoting “+” or “-” .

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Immunohistochemical stains

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CD1a Langerin

• CD1a: majority of cells, including cells with nuclear grooves and nuclear indentations (LC-Langerhans cell) show strong membranous staining

• Langerin: there is strong staining in cells which are also CD1a+

What do you see on the stains?

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Immunohistochemical stains

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S100 CD68 PGM CD163

What do you see on the stains?

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• CD1a: majority of cells, including cells with nuclear grooves and nuclear indentations (LC-Langerhans cell) show strong membranous staining

• Langerin: there is strong staining in cells which are also CD1a+

• S100: positive blush in cells• CD68: majority of cells, including LC, are negative in with a

background of positive cells• CD163: majority of cells, including LC, are negative in with a

background of positive cells

What do you see on the stains?

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What is your final diagnosis?

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• Final diagnosis: Langerhans cell histiocytosis– Given the clinical presentation– Given the histologic morphology of nuclear grooves and nuclear

indentations specific to Langerhan cells– Given the CD1a and Langerin positive immunophenotype for

Langerhan cells

What is your final diagnosis?

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Discussion: Histocytic developmental pathway

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Adapted from Weitzman and Jaffe, 2005

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Algorithm for histocytic lesion in bone for neuropathologists