[Efficacy of neoadjuvant therapy on HER2-positive breast cancer: a clinicopathological analysis].

Objective: To investigate the efficacy of neoadjuvant therapy (NAT) on HER2-positive breast cancer and to analyze their clinicopathological features. Methods: A total of 480 cases of HER2-positive breast cancer who received neoadjuvant therapy (NAT), diagnosed at the Department of Pathology of Fudan University Shanghai Cancer Center from 2015 to 2020, were retrospectively identified. Clinicopathological parameters such as age, tumor size, molecular subtype, type of targeted therapy, Ki-67 proliferation index, ER and HER2 immunohistochemical expression, and HER2 amplification status were analyzed to correlate with the efficacy of NAT. Results: Among 480 patients with HER2-positive breast cancer, 209 achieved pathology complete response (pCR) after NAT, with a pCR rate of 43.5%. Of all the cases,457 patients received chemotherapy plus trastuzumab and 23 patients received chemotherapy with trastuzumab and pertuzumab. A total of 198 cases (43.3%) achieved pCR in patients with chemotherapy plus trastuzumab, and 11 cases (47.8%) achieved pCR in patients with chemotherapy plus trastuzumab and pertuzumab. The pCR rate in the latter group was higher, but there was no statistical significance. The results showed that the pCR rate of IHC-HER2 3+patients (49%) was significantly higher than that of IHC-HER2 2+patients (26.1%, P<0.001). The higher the mean HER2 copy number in the FISH assay, the higher the pCR rate was achieved. The expression level of ER was inversely correlated with the efficacy of NAT, and the pCR rate in the ER-positive group (28.2%) was significantly lower than that in the ER-negative group (55.8%, P<0.001). The pCR rate (29.1%) of patients with luminal B type was lower than that of HER2 overexpression type (55.8%, P<0.001). In addition, higher Ki-67 proliferation index was associated with higher pCR rate (P<0.001). The pCR rate was the highest in the tumor ≤2 cm group (57.7%), while the pCR rate in the tumor >5 cm group was the lowest (31.1%). The difference between the groups was significant (P=0.005). Conclusions: HER2 copy numbers, HER2 immunohistochemical expression level, molecular subtype, ER expression level and Ki-67 proliferation index are significantly associated with pCR after NAT. In addition, fluorescence in situ hybridization results, HER2/CEP17 ratio and tumor size could also significantly affect the efficacy of NAT.

[Invasive breast lobular carcinoma with extracellular mucin: a clinicopathological analysis].

Objective: To study the clinicopathological features of invasive lobular carcinoma (ILC) of the breast with extracellular mucin and outcomes of patients. Method: Clinicopathological features and clinical follow-up (39-123 months and a median follow-up of 55 months) of seven ILC with extracellular mucin were obtained. Hematoxylin-and-eosin (H&E) and immunohistochemistry (IHC) stained sections were reviewed, and fluorescence in situ hybridization (FISH) assay was performed for tumors with HER2 IHC 2+. Patient prognosis was analyzed and literatures related to ILC with extracellular mucin were reviewed. Results: All seven patients were female, aged from 43 to 73 years (median age, 55 years). The tumors ranged in size from 1 to 5 cm (median size 2 cm). All seven cases were of histological grade 2. Most areas of the tumors presented with the morphology of classic ILC, and variable amount of extracellular mucin were observed focally. In six cases, part of the tumor cells contained intracellular mucin, and the nucleus were pushed to one side of the cells, creating the impression of signet-ring cells. Two patients had lymph node metastases at diagnosis, and developed liver and bone metastases at 38th and 48th month, respectively, after surgery, and died at 48th and 123th month, respectively. While the other five patients, except one lost to follow-up, had been disease-free during the follow-up period. IHC results showed estrogen receptor (ER) and progesterone receptor (PR) positivity in 7/7 and 6/7 cases, respectively. Tumors of six patients were HER2 IHC 0/1+. The remaining one was HER2 IHC 2+, while FISH assay revealed HER2 gene amplification in that tumor. The proportion of cases with HER2-positivity was 1/7. The proliferation index Ki-67 ranged from less than 5% to 30%, and Ki-67 less than or equal to 10% were in 5/7 cases. According to the 2013 St. Gallen International Expert Consensus on breast cancer, all tumors were of luminal types; of those, two were luminal A and five were luminal B. Conclusions: ILC with extracellular mucin tends to occur in women over 50 years old. All tumors in the study are grade 2 classic ILC, with signet-ring cells as a common feature. All seven tumors are classified as luminal types, with luminal B as the main molecular subtype.

[Clinicopathologic features of breast lymphoma in core needle biopsy].

Objective: To investigate the clinicopathologic features and differential diagnosis of breast lymphoma in core needle biopsy. Methods: Seventy-two cases of breast lymphoma in core needle biopsy between 2011 and 2016 were extracted from the pathology database of Fudan University Shanghai Cancer Center. The clinicopathologic features were analyzed. The histological diagnosis of the tumors was based on the WHO classifications of tumors of hematopoietic and lymphoid tissues. Immunohistochemistry and molecular methods were performed to detect related antigens and genes. Results: Seventy-one patients were female and one was male. The median age was 54 years. The tumors were located in the right breast in 32 (44.4%) patients and in the left breast in 40 (55.6%) patients. Seven patients had a previous history of lymphoma. Most of the cases presented as a single and painless breast mass. Sixty-three patients received systemic treatment, and nine patients received systemic therapy after excision. The common morphological feature was that single tumor cells infiltrated the stroma, without cohesiveness between tumor cells, and lacking glandular or nested epithelioid structures. The normal ductal and lobular structures of the mammary gland were typically preserved. The tumor cells in some cases were distributed in single rows, and should be differentiated from invasive carcinoma. All cases were positive for LCA, negative for CK. Sixty-eight cases were classified as B-cell lymphoma, including 63 cases (87.5%) of diffuse large B-cell lymphoma (DLBCL; including 3 cases of EBV-positive DLBCL and 60 cases of DLBCL, NOS), two cases of Burkitt lymphoma, one case of mantle cell lymphoma, one case of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue and one case of precursor B lymphoblastic leukemia/lymphoma. The remaining cases included two peripheral T-cell lymphoma (NOS), one extranodal NK/T cell lymphoma, nasal type and one myeloid sarcoma. In 63 cases of DLBCL, 22 cases (34.9%) expressed germinal center B-cell-like (GCB) phenotype and 41 cases (65.1%) showed non-germinal center B-cell-like (non-GCB) phenotype. Conclusions: Core needle biopsy could be the preferred method for diagnosis of breast lymphoma. Diffuse large B-cell lymphoma is the most common histologic type of breast lymphoma, and non-GCB subtype is more frequent than GCB subtype.

[Clinicopathologic study of infiltrating epitheliosis of the breast].

Objective: To evaluate the morphological and immunohistochemical features of infiltrating epitheliosis and its differential diagnosis. Methods: Nine consultation and routine cases of infiltrating epitheliosis diagnosed from January 2015 to December 2016 in Fudan University Shanghai Cancer Center were collected. All tissues were formalin-fixed paraffin-embedded and routinely HE stained. The HE slides were reviewed. Immunohistochemical staining of CKpan, CK7, CK19, CK5/6, CK14, p63, SMMHC, Calponin, ER, PR, HER2, Ki-67 and S-100 protein was performed using Ventana BenchMark automated immunostainer. Results: The morphological features of infiltrating epitheliosis included: (1) Florid proliferation of epithelial cells forming solid nests or papillary, glandular and cord-like pattern. The proliferative cells possessed nuclei of varying size and shape without atypia. (2) The stroma was altered, showing varying degrees of fibrosis or sclerosis. (3) The proliferative epithelial nests might flow into the spaces within small ducts and lobules at the periphery of the lesion, resulting in pseudo-infiltration. Immunohistochemically, infiltrating epitheliosis was non-uniformly positive for ER/PR, and was positive for high molecular weight CK5/6 and CK14. Myoepithelial markers p63, SMMHC and Calponin demonstrated intact, partial or entire loss of myoepithelial cells around the epithelial nests. The loss of myoepithelial markers staining was more frequent at the periphery of the lesion. The most important differential diagnoses included invasive ductal carcinoma, ductal carcinoma in situ (DCIS), and low grade adenosquamous carcinoma, etc. Conclusions: Infiltrating epitheliosis is an important pseudo-infiltrating lesion. The lack of atypia, non-uniform ER/PR expression, positivity for high molecular weight cytokeratins, and the intact to partial to entire loss of myoepithelial markers around the proliferating cell nests are the key points to differentiate it from invasive carcinomas and DCIS.

[Correlation between androgen receptor expression and surrogate molecular subtypes in invasive breast carcinoma].

Objective: To investigate androgen receptor(AR)expression in invasive breast carcinoma and the correlation with surrogate molecular breast carcinoma subtypes. Methods: Immunohistochemical staining of AR and other biomarkers was performed in a cohort of 870 cases of primary invasive breast carcinomas collected from August to December, 2016. The association of AR expression with different histological and surrogate molecular subtypes was analyzed. Results: The positive expression rate of AR in the immunohistochemistry-based surrogate subtypes was 96.3%(207/215) for Luminal A, 89.8%(378/421) for Luminal B, 82.4%(75/91) for HER2 overexpression and 37.1%(53/143) for triple negative breast carcinoma, with significant differences among the four groups (P<0.01). AR correlated positively with the expression of ER(P<0.01), PR(P<0.01), HER2(P=0.007), GATA3(P<0.01), GCDFP15(P<0.01)and mammaglobin(P<0.01), while negatively with the expression of Ki-67(P<0.01), CK5/6(P<0.01)and CK14(P<0.01). Conclusions: AR exhibits a high expression in invasive breast carcinoma, which is mainly correlated with ER-positive breast carcinoma. Regardless of the relatively low expression rate, AR is a potential therapeutic target in triple negative breast carcinoma.

Prognostic factors and treatment comparison in early-stage small cell carcinoma of the uterine cervix.

Small cell carcinoma of the uterine cervix (SCCUC) is rare and its biologic behavior is aggressive. To analyze prognostic factors and determine optimal therapy in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB1-IIA SCCUC, we retrospectively reviewed 96 patients (14 patients treated in our center and 82 patients identified by a search on PubMed) treated with radical surgery (SU), surgery plus adjuvant chemotherapy (SU+Chemo), or surgery plus adjuvant chemotherapy and radiotherapy (SU+Chemo+RT) between 1990 and 2010. Of the 96 patients, 11 patients were treated with SU, 33 with SU+Chemo, and 52 with SU+Chemo+RT. The 5-year survival rate for the 96 patients was 45%. A total of 6% (2/32) of patients had local recurrence, 75% (24/32) had distant metastases, and 19% (6/32) had both. The 5-year survival rate in stage IB1 and IB2-IIA disease was 58 and 34%, respectively (P=0.049). For patients with and without lymph node metastases (LNM), survival was 33 and 60%, respectively (P=0.045). Patients with inner 1/3 stromal invasion had a better survival than those with deep stromal invasion (DSI) (100 vs. 34%, P=0.003). Survival was not significantly different in patients treated with the above three modalities, albeit treatment selection was related to LNM (P=0.000) and DSI (P=0.027). Thus, FIGO stage, LNM and DSI are significant predictors of survival. Adjuvant therapy after SU has not improved survival compared with surgery alone. Thus, newer multimodality therapy should be evaluated.