Challenges in the Histopathologic Diagnosis of Histiocytic Neoplasms

Abstract

Histiocytic neoplasms, including Langerhans cell histiocytosis (LCH), Erdheim-Chester disease (ECD), and Rosai-Dorfman disease (RDD), present a diagnostic challenge due to nonspecific fibroinflammatory infiltrates and a diverse clinical presentation. The pathologist can play a key role in classification of these disorders through multidisciplinary collaboration and correlation of pathologic features with clinical and radiologic findings. The histopathologic differential diagnosis is broad, requiring knowledge of the possible diagnoses at each specific anatomic site, and a careful assessment to exclude other inflammatory and neoplastic disorders. An immunohistochemistry panel including CD163, CD1a, langerin, S100, Factor XIIIa, OCT2, and BRAF V600E can provide definitive diagnosis in LCH and RDD, whereas ECD requires classic clinical features as well as confirmation of an activating MAPK pathway mutation by genetic studies.

MUM1/IRF4 is Highly Expressed in Dermatopathic Lymphadenopathy

“…DL generally self-resolves following the disappearance of the underlying skin stimulus and does not require any specific therapy 1,2. Nevertheless, recognizing DL is important, as the disease can be florid and histologically can potentially mimic other histiocytic lesions, particularly nodal Langerhans cell histiocytosis (LCH) 1,8–11…”

“…1,2 Nevertheless, recognizing DL is important, as the disease can be florid and histologically can potentially mimic other histiocytic lesions, particularly nodal Langerhans cell histiocytosis (LCH). 1,[8][9][10][11] Multiple myeloma oncogene 1 (MUM1), also known as interferon regulatory factor 4 (IRF4), is a helix-loop-helix DNA-binding motif transcription factor that has emerged recently as a key regulator of the immunogenic, as well as tolerogenic functions of Langerhans cells. [12][13][14][15][16] We recently observed high expression of MUM1/IRF4 by paracortical dendritic cells in a case of DL assessed by immunohistochemistry.…”

An Amelanotic Choroidal Lesion in a 68-Year-Old Man

“…Computed tomography and magnetic resonance imaging can also be helpful for diagnosis, as can radiography, which may establish the presence of bone involvement. On histopathology, ECD should be separated from other histiocytic disorders, such as Rosai-Dorfman disease and adult xanthogranulomatous disease . BRAF V600E variation has been identified in up to 60% of ECD cases .…”

Challenging Cases in Neuro-Oncology

“…This is further complicated by extra-nodal Rosai-Dorfman lacking the overall histological architectural features observed in nodal Rosai-Dorfman. [20] It also opens up potential therapeutic opportunities, as this pathway can be targeted with BRAF and MEK inhibitors.…”