Atypia Involving Fibroadenomas: Outcomes and Upgrade Rates.

OBJECTIVE: Fibroadenomas (FAs) involved by atypia are rare. Consensus guidelines for management of FAs involved by atypia when diagnosed on image-guided biopsy do not exist because of limited data reporting surgical upgrade rates to ductal carcinoma in situ (DCIS) or invasive malignancy. Therefore, these lesions commonly undergo surgical excision. METHODS: This single-institution retrospective study identified cases of FAs involved by atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), and/or lobular carcinoma in situ (LCIS) diagnosed on image-guided biopsy between January 2014 and April 2023 to determine upgrade rates. Cases with incidental atypia adjacent to but not involving FAs were excluded. RESULTS: Among 1736 FAs diagnosed on image-guided biopsy, 32 cases (1.8%) were FAs involved by atypia including 43.8% (14/32) ALH, 28.1% (9/32) ADH, 18.8% (6/32) LCIS, 6.3% (2/32) LCIS + ALH, and 3.1% (1/32) unspecified atypia. The most common imaging finding was a mass. Most cases, 81.3% (26/32), underwent subsequent surgical excisional biopsy. A single case of ADH involving and adjacent to an FA was upgraded to FA involved by low-grade DCIS on excision for an overall surgical upgrade rate of 3.8%. There were no cases upgraded to invasive malignancy. For those omitting surgical excision, there was no subsequent malignancy diagnosis at the FA biopsy site over a mean follow-up of 73 months. CONCLUSION: Cases of radiologic-pathologic concordant FAs involved by atypia have a low upgrade rate of 3.8% and should undergo multidisciplinary review. Larger multi-institutional analysis is needed to determine whether guidelines for excision of atypia should apply to atypia involving FAs.

Use of Ultrasound and Ki-67 Proliferation Index to Predict Breast Cancer Tumor Response to Neoadjuvant Endocrine Therapy.

BACKGROUND: Prediction of tumor shrinkage and pattern of treatment response following neoadjuvant endocrine therapy (NET) for estrogen receptor positive (ER+), Her2 negative (Her2-) breast cancers have had limited assessment. We examined if ultrasound (US) and Ki-67 could predict the pathologic response to treatment with NET and how the pattern of response may impact surgical planning. METHODS: A total of 103 postmenopausal women with ER+, HER2- breast cancer enrolled on the FELINE trial had Ki-67 obtained at baseline, day 14, and surgical pathology. A total of 70 patients had an US at baseline and at the end of treatment (EOT). A total of 48 patients had residual tumor bed cellularity (RTBC) assessed. The US response was defined as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). CR or PR on imaging and ≤70% residual tumor bed cellularity (RTBC) defined a contracted response pattern. RESULTS: A decrease in Ki-67 at day 14 was not predictive of EOT US response or RTBC. A contracted response pattern was identified in one patient with CR and in sixteen patients (33%) with PR on US. Although 26 patients (54%) had SD on imaging, 22 (85%) had RTBC ≤70%, suggesting a non-contracted response pattern of the tumor bed. The remaining four (15%) with SD and five with PD had no response. CONCLUSION: Ki-67 does not predict a change in tumor size or RTBC. NET does not uniformly result in a contracted response pattern of the tumor bed. Caution should be taken when using NET for the purpose of downstaging tumor size or converting borderline mastectomy/lumpectomy patients.

Intraoperative sentinel lymph node evaluation in patients with node-positive breast cancer status post neoadjuvant systemic therapy - An institutional experience.

Recent studies have shown the feasibility and utility of sentinel lymph node (SLN) biopsy in patients with biopsy proven node-positive breast cancer after neoadjuvant chemotherapy. We reviewed our experience in intraoperative SLN evaluation in such cases and its effect on axillary management. A retrospective analysis of breast cancer patients (2015-2018) with a biopsy-proven positive axillary lymph node, who received neoadjuvant systemic therapy and underwent intraoperative SLN assessment was performed. Intraoperative SLN assessment results were compared with final pathology. Its accuracy and effect on axillary management is summarized. We identified 106 patients with positive axillary lymph node and neoadjuvant systemic therapy between the ages of 28 and 75 years who had SLN biopsy and lumpectomy (33) or mastectomy (73). Three or more SLNs were identified in 91 cases (86 %). The previously biopsied lymph node was identified as one of the sentinel lymph nodes in 93 cases (88 %). There is a high concordance rate between frozen section diagnosis and final diagnosis on sentinel lymph nodes. No false positive case and seven false negative frozen section diagnosis cases (diagnosed as negative on frozen section and positive on permanent sections) were identified. False-negative frozen section diagnosis correlated with low-volume nodal disease and obscuring tumor bed changes. Almost half of the positive lymph nodes were converted to negative after neoadjuvant chemotherapy. SLN biopsy with intraoperative frozen section evaluation after neoadjuvant systemic therapy in node-positive patients is an effective way to minimize axillary surgery.

Malignancy-associated acquired vulvar lymphangioma circumscriptum: A clinicopathologic study of 71 cases.

BACKGROUND: Acquired lymphangioma circumscriptum of the vulva is rare and can occur subsequent to malignancies of the anogenital and pelvic region. We sought to investigate the clinicopathologic characteristics of malignancy-associated acquired vulvar lymphangioma circumscriptum (AVLC). METHODS: We identified all cases of AVLC within our institution with history of prior malignancy between 2005 and 2021. A similar search was performed in the PubMed database to identify published cases to date. The clinical and histopathologic information was recorded. RESULTS: A total of 71 cases were identified. The most common preceding malignancy was cervical carcinoma (71.8%, 51/71). Radiation therapy was given to 91.4% (64/70) of the patients and lymph node dissection was made on 70.2% (40/57). Median interval between the diagnosis of malignancy and the AVLC was 10 years (range 0-32 years). AVLC frequently presented as vesicular (31.6%, 18/57) or verrucous (28.1%, 16/57) lesions clinically. Common treatments for AVLC included excision (53.1%, 26/49) and laser therapy (16.3%, 8/49), with an overall recurrence rate of 42.9% (24/56) at a median follow-up interval of 1.8 years (range 0.04-32.3 years). CONCLUSION: AVLC is a rare, late complication of anogenital and pelvic malignancies causing debilitating physical symptoms and psychological stress. Further studies are warranted to determine the most effective treatment modalities to mitigate recurrence.

A rare case of group A streptococcal toxic-shock syndrome in a postpartum adolescent leading to multi-organ failure.

Teenage pregnancy is not uncommon, but given the age of the patient, experience, and competency among medical providers varies. While toxic-shock syndrome from group A streptococcus is rare in teenage pregnancy, observed is a gap in care of bridging.

Immunohistochemical profile of breast cancer with respect to estrogen receptor and HER2 status.

There are a few studies that have evaluated a panel of stains on a single large data set of breast cancers, which is required for direct comparison between antibodies. The immunohistochemical panel in this study was chosen to include breast-specific markers and markers that are expressed in tumors resembling breast cancer. The individual marker positivity in decreasing order was 95% (177/186) for GATA-3, 92% (172/186) for cytokeratin (CK)7, 80% (151/189) for AR, 80% for estrogen receptor (158/198), 69% for progesterone receptor (137/198), 55% (105/190) for NY-BR-1, 52% (99/189) for mammaglobin, 31% (59/191) for vimentin, 26% (51/195) for GCDFP-15, 0.5% (1/186) for CK20, and 0% (0/188) for PAX-8. When tumors were categorized based on estrogen receptor and HER2 status; a total of 45 profiles were identified. In addition, some tumors showed an unconventional profile-although the majority of breast carcinomas were CK7-positive/CK20-negative, a CK7-negative/CK20-negative profile was seen in ∼8% of the cases. Such a profile can create confusion in investigation of a carcinoma of unknown origin. The results define the individual sensitivity of each marker and establish a baseline diagnostic profile of breast cancer in a large data set. In addition, the results support the use of immunohistochemical panel for confirming or determining breast as the source of metastasis.

Bariatric surgery-induced weight loss changes immune markers in the endometrium of morbidly obese women.

BACKGROUND: Obesity has been linked to abnormal estrogen regulation, endometrial hyperplasia, and endometrial cancer (EC). Our group has shown that hormone receptor expression profiles in the endometria of morbidly obese women change with weight loss, in some cases concordantly with resolving hyperplasia; however other potential drivers of neoplasia, including altered immunologic tolerance exist. The objective of this study was to evaluate the effect of bariatric surgery induced weight loss on the expression patterns of nonhormone receptor biomarkers associated with cancer and immunity. METHODS: Endometrial biopsies were obtained from 59 asymptomatic, morbidly obese women at the time of bariatric surgery and again 1 year postsurgery. Tissue microarrays were created and immunohistochemical stains for CD3, CD20, and PTEN were performed on all samples and evaluated by 2 blinded pathologists independently. Approximately 50% of participants had sufficient tissue for analysis at both visits. McNemar/Bowker tests of symmetry were performed to compare proportions between categories for matched pairs (pre- and post-treatment). RESULTS: Endometrial hyperplasia was identified in 4 women despite negative clinical histories and resolution of hyperplasia after weight loss occurred in 3 women. While overall no significant differences were observed between matched pre and postsurgery levels of CD20 and CD3 positive cells, a tendency toward decreased expression levels from baseline status was observed for CD20. No differences were observed for PTEN. CONCLUSION: Our data demonstrate that the prevalence of endometrial pathology appears to be partially mitigated by weight loss. Weight loss is associated with alterations in the hormone receptor profiles, but these data suggest that changes in the immune response, as measure be expression of CD20+, may be relevant targets for EC prevention research.

Low ER+ breast cancer: Is this a distinct group?

OBJECTIVES: Estrogen receptor (ER) level can be semiquantified by immunohistochemistry (IHC) using the H-score. The score, given as the sum of the percent staining multiplied by the intensity level, ranges from 0 to 300. METHODS: Forty-nine ER+/HER2- invasive tumors with low ER expression (H-scores of 1-100, representing approximately 5% of all tumors) were studied for various morphologic parameters, progesterone receptor (PR), and Ki-67 IHC. RESULTS: Eighteen of 49 patients received neoadjuvant chemotherapy. The morphologic analysis showed that these tumors are often grade 3 and frequently demonstrate a sheet-like growth pattern, an intratumoral lymphocytic inflammatory infiltrate, and necrosis. Eighty percent of tumors showed a Ki-67 proliferation index of more than 50%, and 94% were PR-. Of the 18 patients who received neoadjuvant chemotherapy, six (33%) achieved pathologic complete response. CONCLUSIONS: The low ER+/HER2- cases have morphologic features and a response to the chemotherapy rate that are more similar to triple-negative tumors than the usual type of ER+ tumors.

Hormone receptor expression patterns in the endometrium of asymptomatic morbidly obese women before and after bariatric surgery.

OBJECTIVE: Obesity increases risk for endometrial neoplasia, but neither the pathophysiology nor the effects of weight loss on the risk are well established. We attempted to characterize the molecular profile of the endometrium of asymptomatic women with morbid obesity before and following bariatric surgery-induced weight loss. METHODS: 59 asymptomatic, morbidly obese women underwent endometrial sampling before bariatric surgery; 46 (78%) of these returned one year later for re-biopsy (median weight loss of 41kg). Duplicate samples from these specimens were scored for expression of estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), and Ki-67 by two independent, blinded pathologists using an H-score [staining intensity (0-3)×(percent of tissue involved)]. RESULTS: The prevalence of hyperplasia pre-operatively was 7% overall and 10% among patients not on an anti-estrogen. ER H-scores were similar before and after surgery overall (median 190 and 196 respectively, p=0.82), but patients with hyperplasia had higher pre-operative H-scores (median 256, p<0.001) and experienced greater H-score drops, than those without hyperplasia (-112 vs +50, p=0.028). In two patients with persistent hyperplasia at one year, ER H-scores fell to levels that were similar to those without pathology. One patient who developed hyperplasia during the study period had a rising ER H-score. Patients with hyperplasia had higher median PR H-scores pre-operatively (284 vs 188, p=0.01), which normalized through greater drops (75 vs 0, p=0.053). AR H-scores dropped significantly after surgery (13 vs 2, p=0.015), but were similar between patients with and without hyperplasia (p=0.33). Weight loss did not affect Ki-67 proliferation index. CONCLUSION: Asymptomatic morbidly obese patients have a high prevalence of occult hyperplasia, characterized by relatively high hormone receptor expression. These profiles appear to normalize with weight loss and in advance of pathologically identifiable changes. These data suggest a potential role for screening this population as well as the possibility that weight loss may be a valid treatment strategy for risk reduction.

Microinvasive breast carcinoma carries an excellent prognosis regardless of the tumor characteristics.

The clinical implication of microinvasive breast carcinoma (MIBC), especially when multiple foci are identified, is still not clearly defined. This study is designed to collect clinicopathologic and follow up data on patients with MIBC. Histologic data including invasive breast cancer type, nuclear grade, number of microinvasive foci and lymph node status, as well as associated in situ component histologic and biomarkers parameters were recorded. Clinical follow-up data, such as local recurrence, distant metastasis and survival was also noted. Forty MIBC cases were identified among 1180 invasive breast cancer cases between 1998 and 2012, representing 3.4% of the overall invasive cases. The majority of the cases (28/40) had three or less foci of microinvasion and had high nuclear grade (26/40). The associated carcinoma in situ was also mostly high grade. The biomarker expression for estrogen receptor/human epidermal growth factor receptor 2 (ER/HER2) of the in situ component was heterogeneous. Of the 35 cases with known nodal status, 1 had macrometastasis, 1 had micrometastasis, 3 had isolated tumor cells, and the remaining had negative nodes. In the follow-up period (mean 30 months, median 15 months) none of the patients had recurrence, distant metastasis or died of disease. In conclusion, MIBC represents a small portion of invasive carcinomas. The majority of cases have high nuclear grade and are associated with high grade ductal carcinoma in situ. The latter doesn't show consistent ER/HER2 expression. Overall, the number of microinvasive foci, the extent and biomarker expression of the in situ component do not appear to impact the overall excellent outcome.

Outcomes of breast cancer patients with micrometastases and isolated tumor cells in sentinel lymph nodes.

BACKGROUND: The prognostic value and clinical implication of micrometastases and isolated tumor cells (ITCs) in sentinel lymph nodes are still not clearly defined. This study was designed to collect clinical pathological data in our Institution. PATIENTS AND METHODS: Twenty-five cases of micrometastases and nine cases of ITCs were identified among 1,000 sentinel lymph node biopsies performed at our institution in the last 10 years. RESULTS: In the 25 patients with sentinel node micrometastases, 12 had completion axillary node dissection, and only one of these twelve had non-sentinel node micrometastasis. In this group, two patients developed local recurrence, and two patients developed distant metastases (one with and one without prior local recurrence) and later died. Both patients had negative non-sentinel lymph nodes. In the 9 patients with sentinel node ITCs, no patient had completion axillary node dissection and no patient developed local or distant metastases. CONCLUSION: Completion axillary node dissection may not be necessary in patients with sentinel node micrometastases and ITCs as it does not impact local recurrence. ITCs do not seem to have prognostic significance. Micrometastases, however, may be associated with local and/or distant metastasis.