Lymph nodes & spleen, nonlymphoma

Lymph node & spleen-nonlymphoid neoplasms

Indeterminate cell histiocytosis / indeterminate dendritic cell tumor


Editorial Board Member: Patricia Tsang, M.D., M.B.A.
Deputy Editor-in-Chief: Genevieve M. Crane, M.D., Ph.D.
Mina Haghighi Abyaneh, M.D.
Ryanne A. Brown, M.D., M.B.A.

Topic Completed: 17 December 2020

Minor changes: 4 March 2021

Copyright: 2003-2021, PathologyOutlines.com, Inc.

PubMed Search: Indeterminate cell histiocytosis[TI] OR indeterminate dendritic cell tumor[TI]

Mina Haghighi Abyaneh, M.D.
Ryanne A. Brown, M.D., M.B.A.
Page views in 2020: 973
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Cite this page: Haghighi Abyaneh M, Mohsin H, Brown RA. Indeterminate cell histiocytosis / indeterminate dendritic cell tumor. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lymphnodesindeterminatecelltumors.html. Accessed October 16th, 2021.
Definition / general
  • Indeterminate cell histiocytosis is an extremely rare neoplastic proliferation of cells of dendritic / histiocytic lineage that share immunophenotypic features of Langerhans cells but lack Birbeck granules and langerin expression
Essential features
  • Skin involvement can be solitary or multifocal
  • Usually restricted to skin, with rare organ or lymph node involvement
  • Indeterminate cells are histopathologically and antigenically similar to Langerhans cells but lack Birbeck granules and langerin (CD207) expression
  • Clinical course varies: spontaneous regression, stable disease, rapid progression or recurrence
Terminology
  • Indeterminate cell histiocytosis
  • Indeterminate cell tumor
  • Indeterminate dendritic cell tumor
ICD coding
  • ICD-10: D76.3 - Other histiocytosis syndromes
Epidemiology
  • Rare neoplasm, with 85 cases reported between 1985 - 2016 (Am J Dermatopathol 2018;40:736)
  • Reported in all age groups, with a median age of 45
  • Near equal M:F
Sites
Etiology
  • Etiology remains uncertain
  • Multiple hypotheses on the relationship between indeterminate cells and Langerhans cells, including:
    • Indeterminate cells are Langerhans cells that have lost their Birbeck granules
    • Indeterminate cells are immature Langerhans cells
  • A subset of cases express dendritic cell marker ZBTB46, raising the possibility that a subset of cases arise directly from bone marrow progenitors as opposed to embryonic precursors that locally renew in the skin (Mod Pathol 2018;31:1479)
  • Association between other hematologic neoplasms has been reported (including B cell lymphoma, T cell lymphoma, acute myeloid leukemia and chronic myelomonocytic leukemia) (Am J Surg Pathol 2008;32:1868, J Cutan Pathol 2017;44:958, Am J Dermatopathol 2019;41:461, Dermatol Res Pract 2010;2010:569345)
  • Indeterminate cell histiocytosis can share clonal abnormality of associated lymphoma or leukemia (Am J Surg Pathol 2008;32:1868)
Clinical features
  • Reported in all age groups with a median age of 45
  • Near equal M:F patients
  • Single cutaneous papulonodule or multiple lesions (few to innumerable)
  • Can have plaques and tumors with leonine facies (J Cutan Pathol 2016;43:158)
  • Usually restricted to skin with rare organ or lymph node involvement
  • Clinical course varies: spontaneous regression, stable disease, rapid progression or recurrence
  • Reference: Am J Dermatopathol 2018;40:736
Diagnosis
  • Skin biopsy for localized lesions
  • Systemic workup to exclude deep involvement
  • CT scans and bone marrow biopsy
Laboratory
Radiology description
  • True cutaneous indeterminate cell histiocytosis typically lacks evidence of deep organ involvement on imaging
Prognostic factors
  • Cases restricted to the skin typically behave indolently
  • Involvement of deep or visceral tissues or bone marrow may portend worse prognosis
Case reports
Treatment
Clinical images

Images hosted on other servers:

Ill defined, erythematous subcutaneous nodule

Microscopic (histologic) description
Microscopic (histologic) images

Contributed by Ryanne A. Brown, M.D., M.B.A.
dermal histiocytoid cells

Dermal histiocytoid cells

histiocytoid cells

Histiocytoid cells

CD68

CD68

CD1a

CD1a

S100

S100

Langerin

Langerin


BRAF V600E

BRAF V600E

Negative stains
Flow cytometry description
  • No known abnormalities in peripheral blood flow cytometry in true cutaneous indeterminate cell histiocytosis
  • For flow cytometry information for cases of chronic myelomonocytic leukemia with an indeterminate cell-like immunophenotype, please refer to Chronic myelomonocytic leukemia
Electron microscopy description
Electron microscopy images

Contributed by Ryanne A. Brown, M.D., M.B.A.
No Birbeck granules

No Birbeck granules

Molecular / cytogenetics description
Sample pathology report
  • Skin, left arm, biopsy:
    • Compatible with indeterminate cell histiocytosis (see comment)
    • Comment: The presence of histiocytes that express CD1a without langerin is compatible with a diagnosis of indeterminate cell histiocytosis (ICH). The definitive etiology of ICH is not known. ICH may represent a distinct entity, as suggested by the detection of ETV3-NCOA2 in a subset of cases (Blood 2015;126:2344) or a variant of Langerhans cell histiocytosis (LCH) that has lost its Birbeck granules. Furthermore, chronic myelomonocytic leukemia (CMML) presenting with skin lesions rarely may mimic the immunohistochemical phenotype of ICH (J Cutan Pathol 2017;44:1075). If clinically indicated, correlation with genomic sequencing to assess for molecular aberrancies characteristic of ICH, LCH or CMML is recommended.
    • Microscopic description: The histologic sections show skin with a nodular infiltrate of epithelioid cells with abundant eosinophilic cytoplasm, vesicular and variably reniform nuclei and prominent nucleoli present in sheets in the superficial and mid dermis. On immunohistochemical staining, the lesional cells are positive for CD1a, S100 and CD68 and are negative for langerin, MPO and BRAF V600E.
Differential diagnosis
Board review style question #1
Electron microscopy reveals Birbeck granules in

  1. Indeterminate dendritic cells
  2. Langerhans cells
  3. Mast cells
  4. Neuroendocrine cells
  5. Merkel cells
Board review style answer #1
B. Langerhans cells. Birbeck granules are characteristically found in the cytoplasm of Langerhans cells. This organelle, when cut in cross section, is often recognizable because of its resemblance to a tennis racquet.

Comment Here

Reference: Indeterminate cell histiocytosis / indeterminate dendritic cell tumor
Board review style question #2

The most useful immunohistochemical marker for differentiating between Langerhans cell histiocytosis and indeterminate dendritic cell tumor (image above) is

  1. CD1a
  2. CD45
  3. CD68
  4. CD207
  5. S100
Board review style answer #2
D. CD207 (langerin) positivity in the Langerhans cells is specific for this disorder. Langerhans cells also typically stain for S100, CD1a and CD68 but CD1a is also expressed in indeterminate cell histiocytosis and CD68 and S100 can be seen in other histiocytic neoplasms. CD45 is a nonspecific leukocyte marker. CD20 is a B cell marker.

Comment Here

Reference: Indeterminate cell histiocytosis / indeterminate dendritic cell tumor
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