Bone
Hematologic neoplasms
Anaplastic large cell lymphoma (ALCL)

Author: Sheren Younes, M.D. (see Authors page)

Revised: 7 November 2016, last major update December 2013

Copyright: (c) 2003-2016, PathologyOutlines.com, Inc.

PubMed search: anaplastic large cell lymphoma [title] bone

Cite this page: Anaplastic large cell lymphoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/boneanaplasticlymphoma.html. Accessed December 6th, 2016.
Definition / General
  • ALCL is a neoplasm of T-cell or null cell lineage with strong expression of cytokine receptor CD30
  • Widely involves nodal and extranodal sites, see Lymphoma chapter
  • Primary and secondary bone involvement by ALCL is rare
  • ALCL occurring in bone can be ALK positive or negative
  • Poor prognosis, even if ALK positive
Epidemiology
  • Mean age 33 years, wide age range
    • ALK+ ALCL occurs in the first 3 decades of life
    • ALK− ALCL peaks ~6th decade of life
  • Males > Females, but ALK− cases have lower male predominance than ALK+ cases
Etiology
  • No clearly identified risk factor; EBV and other viruses seem to play no role in ALCL development
  • Not an HIV related lymphoma, although poor prognosis if ALCL and HIV+
Pathophysiology
  • ALK+ ALCL have molecular abnormalities involving ALK, located at chromosome 2p23, leading to ALK overexpression, oncogenic effect
  • Most common translocation is t(2;5)
  • ALK− ALCL pathogenesis is poorly understood
Clinical Features
  • Primary or secondary
  • Solitary or multiple bony lesions with related dysfunction
  • Tumor may involve multiple skeletal sites
  • Axial bone predilection
Radiology Description
  • Usually lytic bone lesion(s)
  • Soft tissue extension may be seen
  • Osteolytic lesions, often multiple
  • May involve axial bones
Prognostic Factors
  • Overall prognosis of bone ALCL is poor
  • Stage at presentation, using Ann Arbor staging, has strong predictive value
  • Generally ALK+ ALCL has longer failure free survival (FFS) and overall survival (OS) than ALK− ALCL (70% - 80%, and 33% - 49% respectively), but ALK positivity is not favorable for primary bone ALCL (Mod Pathol 2000;13:1143)
  • For primary bone ALCL, younger patients have better prognosis, International prognostic Index (IPI) is useful
Case Reports
Treatment
  • Chemotherapy and radiotherapy regimens used for aggressive lymphoma
  • Anti CD30 therapy (BioDrugs 2014;28:181)
Clinical Images
Images hosted on other servers:

Osteolytic bone lesion

Gross Description
  • Mass destroying bone
  • May extend to surrounding soft tissue
Micro Description
  • Diffuse sheets and clusters of highly pleomorphic lymphoid cells with various morphologic patterns
  • Variable numbers of large cells
  • Cytoplasm is abundant, clear, amphophilic to deeply basophilic
  • Nucleus is large, often eccentric, round, lobulated, bizarre, chromatin poor
  • Nucleoli are small to prominent, can be inclusion-like
  • High mitotic rate, atypical mitoses
  • Hallmark (characteristic) cells are large with kidney shaped or "pig embryo" nucleus partially surrounding a cytoplasmic pale-staining paranuclear hof
  • Reed-Sternberg-like cells may be seen
  • Variable proportion of mixed inflammatory cells
  • Monomorphic pattern, with large cells that are not bizarre or lobulated, has been described in bone (Arch Pathol Lab Med 2000;124:1339)
  • Morphology similar in ALK + and ALK− cases
Micro Images
Images hosted on other servers:

Diffuse infiltration by mononuclear tumor cells

CD30, EMA, granzyme B, ALK1

H&E, CD30+, ALK+

Cytology Description
  • Large cells with basophilic cytoplasm, cytoplasmic vacuoles
  • Round, lobulated nuclei; nucleoli can be prominent
  • Hallmark cells can be appreciated
Positive Stains
  • CD30 positive in all cases
    • Strong membrane and golgi pattern
    • Non specific, can be also positive in other reactive and neoplastic lesions
  • ALK may be positive or negative
    • Staining pattern is variable
    • Membranous or cytoplasmic, depending on translocation
    • Nuclear staining in small cell variant
  • Most cases express one or more T cell markers
  • Some show null cell phenotype
  • Cytotoxic markers of TIA, perforin, granzyme are positive
  • EMA is positive in most cases
Negative Stains
Flow Cytometry Description
  • Similar to immunohistochemistry
  • CD45 positive
  • ALK cannot be completely assessed by flow
  • CD13 is commonly expressed
  • CD26 is common in ALK+ ALCL
Electron Microscopy Description
  • Cells resemble those of classic Hodgkin lymphoma
  • CD30+ in cell membrane and golgi complex (by gold labeling)
Molecular / Cytogenetics Description
  • 90% clonal TCR gene rearrangement (ALK+ and ALK−)
  • ALK+: t(2;5)(q23;q35) translocation in 20% - 60%; at least 11 variant translocations involving ALK genes as t(1;2), t(2;3), and inv 2
  • ALK−: no molecular abnormality detected
  • ALK positive and ALK negative variants have different gene expression profiling (GEP) signatures
Molecular / Cytogenetics Images
Images hosted on other servers:

FISH of t(2;5)

Differential Diagnosis