DISCUSSION
PBL, first defined by Wiseman and Liao (1), requires the primary lesion
to be within the breast with or without regional nodal involvement but
no other extramammary sites of involvement and no antecedent diagnosis
of lymphoma. PBL tumors are classified as either Stage I
(breast-limited) or stage II (limited to breast and ipsilateral axillary
ganglia (2)). Based on the SEER database, the overall incidence of PBL
is 1.35/1,000,000 with a significant upward trend from 1975 to 2017 (3).
PBS accounts for <0.5 % of breast neoplasms and 2.2% of
extranodal lymphomas (4,5) Asynchronous bilateral PBL has only rarely
been reported. In this case report, there was a hiatus of 27 years
between diagnoses of PBL. To our knowledge, the longest interval between
asynchronous PBL was previously 11.5 years (5).
The average age at presentation for PBL is in the fifth and sixth decade
of life (6). Most are women, but male PBS has been reported (7). Most
PBL presents with a painless, enlarging breast mass and is found more
commonly in the right breast compared to the left (8). Most patients do
not present with B symptomatology (9,10). Bilateral involvement at
presentation occurs in approximately 11% of PBL cases and more commonly
affects younger women during pregnancy or in the postpartum period (11).
Mammogram and ultrasound are non-specific, usually showing a single
ovoid, hyperdense mass with or without adenopathy (12).
B-cell PBLs are more common than T-cell subtype. Pathologically, 50%
are DLBCL, followed by follicular lymphoma, and extranodal marginal zone
lymphoma (2). Excisional biopsy and core biopsy are the preferred
techniques for adequate tissue acquisition. Fine needle aspiration (FNA)
is not recommended because although it may differentiate lymphoma from
breast carcinoma, the FNA sample lacks architectural detail to
accurately classify lymphoma subtypes (13).
The management of PBL has not been standardized; however, most authors
recommend diagnostic biopsy followed by chemotherapy and radiotherapy
(14). Since DLBCL is the most common histopathological subtype, R-CHOP
remains the first-line treatment regimen (15). For patients who undergo
initial surgery management, adjuvant chemotherapy and radiation should
be recommended to prevent recurrence. Radical mastectomy is not thought
to have improved outcomes compared to simple resection (16). Central
nervous system (CNS) relapse is increased in PBL (17), occurring in
5-16% of cases (16-20), and usually occurs within two years following
completion of therapy (17). Currently, the NCCN guideline V 5.2023 gives
a category 2A recommendation for CNS prophylaxis in DLBCL for high-risk
patients based on the CNS International Prognostic Index (CNS-IPI) or
should be considered for patients with Stage 1E DLBCL of the breast
(21), which is what our patient had. Still, the role of CNS prophylaxis
remains controversial (13). According to Schmitz et al, the CNS-IPI has
low positive predictive value between 10-12% (22). There is no
consensus on route of CNS administration. Intravenous methotrexate
versus intrathecal methotrexate does not seem to yield significant
differences in outcome (23). CNS prophylaxis also has potential for
toxicities such as renal impairment, delayed methotrexate clearance,
post- lumbar puncture headaches, mucositis, and rarely hematologic
toxicities, all of which could lead to delays in therapy (24). In our
case, mutual decision was made not to undertake CNS prophylaxis.
There is limited evidence on prognostic factors in PBL. High stage
disease (including nodal and/or bilateral breast involvement at
presentation), larger tumor size, elevated LDH, poorer performance
status, and CNS relapse is associated with worse outcomes (25). The
5-year overall survival rate for PBL with diffuse large B-cell subtype
is between 50-60% (20).
Due to the rarity of PBL, a predictive genetic signature is difficult to
determine. According to Zhang et al, the presence and frequency of
certain high-mutant somatic genes including PIM1, MYD88, DTX1, CD79B,
KMT2D, TNFAIP3, and ITKB, do however seem to correlate with age at
presentation, pathologic subtype, and have tendency to shorten overall
survival and progression free survival in PBL (26). In our case, these
somatic genes were not assessed. This appeared to be a germinal center
diffuse large B-cell subtype without any unfavorable features noted on
IHC or FISH.