Anaplastic large cell lymphoma classification

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sowminya Arikapudi, M.B,B.S. [2]

Overview

Anaplastic large cell lymphoma may be classified into several subtypes based on immunophenotype, clinical presentation, and histology.

Classification

  • Anaplastic large cell lymphoma (peripheral T-cell lymphoma Non-Hodgkin Lymphoma) may be classified into 2 subtypes:
  • Based on clinical presentations, anaplastic large cell lymphoma may be classified into 3 subtypes:[1][2]
  • Primary cutaneous anaplastic large cell lymphoma
  • Primary systemic anaplastic large cell lymphoma
  • Nodal anaplastic large cell lymphoma
  • Extra nodal anaplastic large cell lymphoma
  • Implant associated anaplastic large cell lymphoma
  • Based on histology, anaplastic large cell lymphoma may be classified into 3 subtypes:
  • Classical Variants
  • Atypical Variants
  • Rare Variants
Classification based on the clinical presentation[1]
Name Description
Primary cutaneous anaplastic large cell lymphoma
  • Confined to the skin
  • Usually a single lump or tumor in the skin
  • May also spread to lymph nodes in the area
  • Associated with a rare skin condition called lymphomatoid papulosis
  • Less aggressive than primary systemic anaplastic large cell lymphoma
  • Occasionally individuals have a spontaneous remission
  • Fairly good prognosis
Primary systemic anaplastic large cell lymphoma
  • Usually involves the lymph nodes
  • Can also occur in organs or tissues other than the lymph nodes (extranodal sites), including: lungs, liver, bone marrow, bone, gastrointestinal tract, skin, and soft tissue
  • Most individuals have advanced stage (stage III or IV) disease when they are diagnosed
  • Usually a fast-growing (aggressive) lymphoma
Implant associated anaplastic large cell lymphoma
  • The tumor initially manifests with swelling of the breast due to fluid accumulation around the implant
  • May progress to invade the tissue surrounding the capsule, and if left untreated may progress to axillary lymph nodes[3]
Histologic Classification [4][5]
Name Description
Classical Variants
Common pattern
  • ALK positive anaplastic large cell lymphoma
  • Most common morphological variant (75%)[6]
  • In large cells, nucleoli tend to be more prominent
  • The cytoplasm may be either basophilic or eosinophilic and the cell may have many nuclei with dispersed or clumped chromatin
  • Given that the lymphomatous cells grow in the lymph node's sinuses, this variant may ressemble a metastatic tumor
Atypical Variants
Small cell
  • ALK positive anaplastic large cell lymphoma
  • Cells have nuclear irregularity and perivascular/intravascular distribution[7]
  • Occasionally, lymphomatous cells have a pale cytoplasm with a central nucleus, described as "fried egg cell"[5]
Lymphohistiocytic
  • ALK positive anaplastic large cell lymphoma
  • Histiocytes have an acidophilic cytoplasm and a perinuclear clear area, with an eccentric nuclei and condensed chromatin[8]
  • Lymphomatous cells cluster around the perivascular area as demonstrated by immunostaining with CD30 and ALK antibodies[5]
Giant cell
  • ALK positive anaplastic large cell lymphoma
Hodgkin's like
  • The morphological characteristics of this pattern are similar to the nodular sclerosis variant of Hodgkin's lymphoma[9]
  • This pattern is predominately more common among females
  • There are two immunophenotypes:[9]
    • Positive: CD30, ALK, epithelial membrane antigen (EMA), CD43 (only 66% of the times), and perforin
    • Negative: CD15, CD20, Pax5/BSAP, and EBV
Rare Variants
Sarcomatoid
  • ALK positive anaplastic large cell lymphoma

References

  1. 1.0 1.1 Anaplastic large cell lymphoma. Canadian Cancer Society. http://www.cancer.ca/en/cancer-information/cancer-type/non-hodgkin-lymphoma/non-hodgkin-lymphoma/types-of-nhl/anaplastic-large-cell-lymphoma/?region=on Accessed on October 7, 2015
  2. Anaplastic large cell lymphoma. Wikipedia. https://en.wikipedia.org/wiki/Anaplastic_large-cell_lymphoma Accessed on October 19, 2015
  3. Miranda RN, Aladily TN, Prince HM, Kanagal-Shamanna R, de Jong D, Fayad LE,Amin MB, Haideri N, Bhagat G, Brooks GS, Shifrin DA, O'Malley DP, Cheah CY, Bacchi CE, Gualco G, Li S, Keech JA Jr, Hochberg EP, Carty MJ, Hanson SE, Mustafa E, Sanchez S, Manning JT Jr, Xu-Monette ZY, Miranda AR, Fox P, Bassett RL, Castillo JJ, Beltran BE, de Boer JP, Chakhachiro Z, Ye D, Clark D, Young KH, Medeiros LJ. Breast implant-associated anaplastic large-cell lymphoma: long-term follow-up of 60 patients. J Clin Oncol. 2014 Jan 10;32(2):114-20.
  4. The anaplastic lymphoma kinase in the pathogenesis of cancer. http://go.galegroup.com/ps/retrieve.dosgHitCountType=None&sort=RELEVANCE&inPS=true&prodId=HRCA&userGroupName=mlin_b_bethidmc&tabID=T002&searchId=R1&resultListType=RESULT_LIST&contentSegment=&searchType=AdvancedSearchForm&currentPosition=1&contentSet=GALE%7CA188154738&&docId=GALE Accessed on October 8, 2015
  5. 5.0 5.1 5.2 Swerdlow, Steven (2008). WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon, France: International Agency for Research on Cancer. ISBN 9789283224310. 
  6. Falini B, Bigerna B, Fizzotti M, Pulford K, Pileri SA, Delsol G; et al. (1998). "ALK expression defines a distinct group of T/null lymphomas ("ALK lymphomas") with a wide morphological spectrum.". Am J Pathol. 153 (3): 875–86. PMC 1853018Freely accessible. PMID 9736036. doi:10.1016/S0002-9440(10)65629-5. 
  7. Kinney MC, Collins RD, Greer JP, Whitlock JA, Sioutos N, Kadin ME (1993). "A small-cell-predominant variant of primary Ki-1 (CD30)+ T-cell lymphoma.". Am J Surg Pathol. 17 (9): 859–68. PMID 8394652. 
  8. "Frequent Expression ofthe NPM-ALK Chimeric Fusion Protein inAnaplastic Large-Cell Lymphoma, Lympho-Histiocytic Type" (PDF). 
  9. 9.0 9.1 Vassallo J, Lamant L, Brugieres L, Gaillard F, Campo E, Brousset P; et al. (2006). "ALK-positive anaplastic large cell lymphoma mimicking nodular sclerosis Hodgkin's lymphoma: report of 10 cases.". Am J Surg Pathol. 30 (2): 223–9. PMID 16434897. 

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