Faculty Bibliography

Amyloidosis is characterized by extracellular deposition of insoluble protein fibrils in a beta-pleated sheet configuration. Breast amyloidosis is a rare entity which has previously been reported to present with localized involvement, or as a late manifestation of systemic amyloidosis. However, descriptions of the clinicopathologic features of localized breast amyloidosis remain limited. A retrospective search for breast amyloidosis diagnosed at our institution yielded 10 cases of breast amyloidosis. All patients were female, with a mean age of 69. Median follow-up for survival or progression was 13 months. Indications for breast or axilla biopsy included mammographic calcifications, mass, and axillary lymphadenopathy. Amyloid showed positive staining with Congo red in all cases, and amyloid typing revealed light chain lambda in 3 cases, amyloid transthyretin in 2 cases, light chain kappa in 1 case, and iatrogenic insulin-derived amyloidosis in 1 case. Amyloid occurred within axillary lymph nodes and alongside both benign and neoplastic breast tissue, including atypical ductal hyperplasia, lobular carcinoma in situ and ductal carcinoma in situ. Most cases were associated with predisposing clinical conditions, including autoimmune disease in 4 cases, B cell lymphomas in 2 cases, and diabetes mellitus treated with insulin in 1 case. In contrast to previously published case series, no patient had clinical evidence of systemic amyloidosis. Amyloidosis of the breast should be considered in the differential diagnosis of all mammographic calcifications and masses of the breast or axilla. When recognized correctly on biopsy, the diagnosis of amyloidosis can not only prevent further unnecessary surgical interventions due to radiology-pathology discordance, but initiate the necessary amyloidosis work-up. Although rare, an awareness of the clinicopathologic characteristics of this easily overlooked entity is of great importance for every practicing pathologist reviewing breast biopsies.

BACKGROUND:Growing evidence suggests that the tumor immune microenvironment influences breast cancer development and prognosis. Density of tumor-infiltrating lymphocytes (TILs) within invasive breast cancer is correlated with response to therapy, especially in triple-negative disease. The clinical relevance and outcomes of TILs within ductal carcinoma in situ (DCIS) are less understood. METHODS:Our institutional database of 668 patients with pure DCIS from 2010 to 2018 was queried. TILs were evaluated by International TILs Working Group guidelines. Percentage of TILs was assessed from the densest focus (hotspot) in one high-power field of stroma touching the basement membrane. Statistical methods included cluster analyses (to define sparse versus dense TILs), logistic, and Cox regression models. RESULTS:Sixty-nine patients with DCIS and TILs were evaluated, of whom 54 (78%) were treated by breast-conserving surgery. Thirteen (19%) patients had ipsilateral recurrence. Each recurrence (n = 13) was matched to four controls (n = 56) based on date of surgery. Median follow-up was 6.7 years. TILs were defined as sparse (< 45%) or dense (≥ 45%). Dense TILs were associated with younger age (p = 0.045), larger tumor size (p < 0.001), high nuclear grade (p = 0.010), comedo histology (p = 0.033), necrosis (p = 0.027), estrogen receptor (ER) negativity (p = 0.037), and ipsilateral recurrence (p = 0.001). Nine patients with dense TILs had mean time to recurrence of 73.5 months compared with four patients with sparse TILs with mean time to recurrence of 97.9 months (p = 0.003). CONCLUSIONS:Dense TILs were significantly associated with age, tumor size, nuclear grade, comedo histology, necrosis, and ER status and was a significant predictor of recurrence in patients with pure DCIS.

Background/Objective: Growing evidence suggests that tumor immune-microenvironment influences breast cancer carcinogenesis and prognosis. Density of tumor-infiltrating lymphocytes (TILs) within invasive breast cancer correlates with response to therapy, especially in triple-negative disease. The clinical relevance and outcomes of TILs within ductal carcinoma in situ (DCIS) is less understood.
Method(s): Our institutional database was queried for pure DCIS from 2010-2018 (n=668). Local recurrences (n=13) were matched 1:4 to patients without recurrence. TILs were evaluated by the International TILs Working Group Guidelines. Percentage of TILs was assessed from the densest focus in 1 high-power field of stroma touching the basement membrane. Statistical methods included cluster analyses, logistic, and Cox regression models.
Result(s): Sixty-nine patients, including the 13 recurrences were evaluated. Fifty-four (78%) were treated by breast-conserving surgery (BCS). The median follow-up was 6.7 years. TILs were defined as sparse (<45%) and dense (>=45%). Dense TILs was associated with younger age (p=0.045), larger tumor size (p<0.001), high nuclear grade (p<0.001), comedo histology (p=0.016), necrosis (p=0.038), and recurrence (p=0.001). Nine patients with dense TILs had a mean time to recurrence of 74 months compared to 4 patients with sparse TILs who had a mean time to recurrence of 93 months (p=0.044) (Figure).
Conclusion(s): We found that dense TILs in DCIS was significantly associated with age, tumor size, grade, and histology. Most importantly, dense TILs are a significant predictor of recurrence in patients with DCIS, which underlies the prognostic importance of the immune microenvironment of early breast cancers. (Figure Presented)