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Breast Implant-Associated Anaplastic Large Cell Lymphoma

Posted on March 21 2016

Implant-associated anaplastic large cell lymphomas represent an extremely rare but well-documented complication of prosthetic breast implants. When presenting as an isolated fluid effusion in the absence of extracapsular tissue invasion or mass lesions, these neoplasms have been associated with a uniquely favorable clinical course.

Clinical History:

The patient is a 47-year-old female with a previous history of invasive ductal carcinoma of the breast, status post bilateral mastectomy and reconstructive surgery with prosthetic breast implants, now presenting with a right breast serous effusion. Specimens submitted to MPLN for flow cytometric studies consultation included right breast fluid (serosanguinous, 30 ml), left breast fluid (5 ml, straw colored), and portions of pericapsular soft tissue from the right and left breast.

Microscopic Findings:

Morphologic review of the right breast fluid cellular cytospin demonstrates a densely cellular proliferation composed predominantly of highly anaplastic large cells with often vacuolated cytoplasm and variably prominent nucleoli. Some candidate hallmark cells are noted.

The left breast fluid (not shown) was relatively paucicellular and showed mostly just occasional numbers of small, mature-appearing lymphocytes, plasma cells, and some histiocytes. The left and right breast pericapsular tissue specimens demonstrated fibroconnective tissue with mild chronic inflammation and no evidence of infiltration by the large cells identified in the right breast fluid.

Special Studies:

Flow cytometry

  • The right breast fluid shows an atypical CD30+ lymphoid population with increased forward and side scattered light characteristics comprising approximately 81% of total cellular events. Immunophenotype of the atypical cells:
  • CD45+ (bright), CD1a-, CD2+ (bright), sCD3-, icCD3-/+, CD4-/+, CD5-, CD7-, CD8-, CD10-, CD19-, CD20-, CD30+, CD34-,CD38-/+, CD117-, CD16-, CD56-, MPO-, TdT-
  • No immunophenotypically aberrant CD30+ population was identified on flow cytometric evaluation of the left breast fluid, or the right and left breast pericapsular soft tissue specimens.

Immunohistochemistry

An ALK immunohistochemical stain was performed on a paraffin cell block prepared from the right breast fluid. The malignant large cells are ALK negative.

Cytogenetics

Classical cytogenetic analysis of the right breast fluid was attempted to further assess for a potential ALK gene rearrangement.However, an absence of metaphase cellular growth precluded evaluation.  An ALK FISH study was also recommended but no order was received from the referral institution.

Differential Diagnosis

The possibility of localized involvement by systemic lymphoma must always be considered in cases such as this. In general, differential diagnostic considerations for CD30+ lymphoproliferative disorders may include anaplastic large cell lymphoma, ALK+ or ALK-; CD30+ PTCL, NOS; CD30+ cutaneous lymphoproliferative processes (e.g. large cell transformation mycosis fungoides, or lymphomatoid papulosis, among others); or primary cutaneous extranodal NK-T-cell lymphomas, nasal type.  CD30 expression may also be seen in Classical Hodgkin lymphomas, and some diffuse large B-cell lymphomas. However, these latter entities were not strongly considered in this case due to the lack of B-cell marker expression in the neoplastic cells, together with the clinical presentation of an isolated, unilateral fluid accumulation involving the right breast cavity. 

Diagnosis

The right breast fluid flow cytometry study results were interpreted as “CD30+ lymphoproliferative disorder, immunophenotypically compatible with implant-associated anaplastic large cell lymphoma.” Clinicopathologic correlation is critical for accurate diagnosis of this rare entity. The referral pathologist and clinicians were therefore specifically advised that morphologic evaluation would be required to further assess for extracapsular tissue invasion, and also, that clinical staging will be necessary to further assess for mass lesions, pathologic lymphadenopathy, or peripheral disease elsewhere. This patient was found to have disease truly isolated and confined to the right breast implant site in the form of a unilateral seroma, compatible with our reported interpretation of the flow cytometric findings.

Educational Comments

ALCL, in general, comprises approximately only 3% of adults NHLs. The implant-associated subtype is vanishingly rare, with some studies documenting its incidence as 0.04% of NHLs.  These lesions have been seen in association with both saline and silicone prosthetic breast implants, and the time to presentation after prosthetic implantation is variable, ranging from 1 to 20+ years in the reported medical literature. No specific patient age predilection has been established for this neoplasm.

Implant-associated ALCLs show immunophenotypic features overlapping with classical ALCLs. In contrast to classical ALCL, however, implant-associated ALCLs are usually negative for ALK protein overexpression or ALK translocations, and lesions presenting as isolated fluid effusions are associated with a uniquely favorable clinical course.  Implant removal and capsulectomy typically results in clinical resolution of disease, without the need for aggressive medical management including chemotherapy or radiation. Although extremely rare, implant-associated ALCLs have been further subcategorized based on the presence of absence of extracapsular tissue invasion and associated mass lesions. In one recent study, 2-year overall survival was noted as only 52.5% among implant-associated ALCL patients whose lymphomas demonstrated extracapsular tissue invasion and formation of mass lesions  Patients with noninvasive disease restricted to the seroma cavity showed 100% survival at 2 years follow-up (Ann Oncol. 2016 Feb;27(2):306-14).

In summary, a high index of suspicion based on the clinicopathologic features is required for accurate diagnosis of this rare and exotic lymphoma subtype. Close clinical follow-up and clear communication between the referral hematopathologist and their clinical colleagues are also extremely important for optimal patient management.

Relevant Literature

Right breast fluid flow sample

right breast fluid flow sample

Flow Cytometry Study Results, Right Breast Fluid

Right breast fluid cell block H&E and ALK immunohistochemistry

 

Case study by Bevan Tandon, MD


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