Testis and epididymis
Other tumors not specific to testis
Anaplastic large cell lymphoma

Author: Jennifer Gordetsky, M.D. (see Authors page)

Revised: 19 July 2017, last major update August 2013

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed Search: Testis anaplastic large cell lymphoma

Cite this page: Anaplastic large cell lymphoma. PathologyOutlines.com website. http://pathologyoutlines.com/topic/testisALK.html. Accessed October 22nd, 2017.
Definition / general
  • ALK+ anaplastic large cell lymphoma (ALCL) is a peripheral T cell lymphoma consisting of large neoplastic cells with abundant cytoplasm and pleomorphic, often horseshoe shaped nuclei with a translocation involving the anaplastic lymphoma kinase (ALK) gene, expression of ALK protein and CD30 (Crit Rev Oncol Hematol 2012;83:293)
  • ALK- ALCL has similar morphologic and phenotypic features but lacks the ALK rearrangement and ALK protein expression (Crit Rev Oncol Hematol 2013;85:206)
Epidemiology
Sites
  • Mostly affects lymph nodes, rare in testis
  • Extranodal involvement is observed in 60% of ALK+ cases and 20% of ALK- cases
  • Soft tissue and bone are the most common extranodal sites for ALK+
  • Skin, liver and lung are the most common extranodal sites for ALK-
  • Central nervous system localization is rare (Crit Rev Oncol Hematol 2012;83:293, Crit Rev Oncol Hematol 2013;85:206)
Pathophysiology
  • ALK, a receptor tyrosine kinase in insulin receptor superfamily, was originally identified in ALCL as oncogenic ALK fusion protein due to a t(2;5) chromosomal translocation
  • Other chromosomal rearrangements or gene mutations / amplifications lead to enhanced ALK activity and have been identified in ALCL (Crit Rev Oncol Hematol 2012;83:293)
Etiology
  • No particular risk factors or viruses identified
Clinical features
  • Testicular swelling and B symptoms (fever, night sweats, > 10% weight loss)
  • Both ALK+ and ALK- ALCL patients tend to present with high stage disease
  • ALK- patients have a much worse prognosis than ALK+
  • 5 year failure free survival is 60% (ALK+) and 36% (ALK-, Crit Rev Oncol Hematol 2012;83:293) although rarity of disease makes prognosis uncertain
Diagnosis
  • Testicular mass with large, CD30+ tumor cells with abundant cytoplasm and pleomorphic, often horseshoe shaped nuclei
  • ALK+ ALCL has t(2;5) / NPM-ALK translocation, 90% show clonal TCR rearrangement; usually EMA+, positive for cytotoxic markers (TIA1, Granzyme B, perforin) and expresses one or more T cell antigens although some may have "null" phenotype; EBV-
  • ALK- ALCL has strong CD30+, PAX5- tumor cells (Hodgkin lymphoma is CD30+ but PAX5+)
Laboratory
  • Patients with nodal disease may have elevated LDH (not reported in 3 cases of testicular ALCL)
Radiology description
  • Ultrasound is imaging modality of choice
  • Complete staging and workup is similar to that routinely used for nodal NHL, includes total body computerized tomography
  • CNS MRI or CT scan is indicated in patients with neurological symptoms
Radiology images

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Ultrasound

Prognostic factors
  • Favorable prognosis with NPM-ALK expression although rare so prognosis uncertain
  • Other factors include age, performance status, LDH level, bone marrow involvement
  • Extranodal site of disease is associated with worse survival
Case reports
Treatment
Gross description
Gross images

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Microscopic (histologic) description
  • Normal architecture is effaced by solid, cohesive sheets of neoplastic cells
  • Tumor cells are large, with abundant cytoplasm and pleomorphic nuclei, often horseshoe shaped
  • Tumor cells tend to have intertubular growth pattern (Am J Surg Pathol 1994;18:376, figure 5)
  • Sclerosis or eosinophilia may occur
  • J Pediatr Hematol Oncol 2009;31:330, figures 1 and 2
Microscopic (histologic) images

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Not testis

Not testis

CD30

CD30, CD99

Cytology description
  • Large lymphoid cells with chromatin poor, horseshoe shaped nuclei containing multiple nucleoli
  • Cells with these cytologic features have been called "hallmark cells" because they are encountered in all ALCL variants
  • A large number of tumor cells contain > 1 nucleus
Cytology images

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H&E, CD30, perforin, ALK

Positive stains
  • CD45, CD3, CD30 (membranous), EMA
  • t(2;5) / NPM-ALK translocation cases have cytoplasmic and nuclear ALK staining of large cells
  • Cases with variant translocations have variable subcellular distribution of ALK (membranous or cytoplasmic)
Negative stains
Flow cytometry description
  • CD30+ with aberrant T cell antigen expression (CD2, CD3, CD4, CD5 and CD7)
  • CD3 antigen often dimly expressed compared with background normal T cells
  • Frequent CD25 expression (Oncol Lett 2013;5:515)
Flow cytometry Images

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Lymph node biopsy

Molecular / cytogenetics description
  • 90% of ALK+ ALCL show clonal rearrangement of TCR genes
  • Most frequent genetic alteration is t(2;5)(p23;q35), between ALK gene on #2 and nucleophosmin (NPM) gene on #5
  • Variant translocations involving ALK and other partner genes on chromosomes 1, 2, 3, 17, 19, 22 and X also occur
  • All these translocations result in upregulation of ALK
Differential diagnosis