Could breast multiparametric MRI discriminate between pure ductal carcinoma in situ and microinvasive carcinoma?

BACKGROUND: Ductal carcinoma in situ (DCIS) is often reclassified as invasive cancer in the final pathology report of the surgical specimen. It is of significant clinical relevance to acknowledge the possibility of underestimating invasive disease when utilizing preoperative biopsies for a DCIS diagnosis. In cases where such histologic upgrades occur, it is imperative to consider them in the preoperative planning process, including the potential inclusion of sentinel lymph node biopsy due to the risk of axillary lymph node metastasis. PURPOSE: To assess the capability of breast multiparametric magnetic resonance imaging (MP-MRI) in differentiating between pure DCIS and microinvasive carcinoma (MIC). MATERIAL AND METHODS: Between January 2018 and November 2022, this retrospective study enrolled patients with biopsy-proven DCIS who had undergone preoperative breast MP-MRI. We assessed various MP-MRI features, including size, morphology, margins, internal enhancement pattern, extent of disease, presence of peritumoral edema, time-intensity curve value, diffusion restriction, and ADC value. Subsequently, a logistic regression analysis was conducted to explore the association of these features with the pathological outcome. RESULTS: Of 129 patients with biopsy-proven DCIS, 36 had foci of micro-infiltration on surgical specimens and eight were diagnosed with invasive ductal carcinoma (IDC). The presence of micro-infiltration foci was significantly associated with several MP-MRI features, including tumor size (P <0.001), clustered ring enhancement (P <0.001), segmental distribution (P <0.001), diffusion restriction (P = 0.005), and ADC values <1.3 × 10-3 mm2/s (P = 0.004). CONCLUSION: Breast MP-MRI has the potential to predict the presence of micro-infiltration foci in biopsy-proven DCIS and may serve as a valuable tool for guiding therapeutic planning.

The value of microendoscopy in the diagnosis of cervical precancerous lesions and cervical microinvasive carcinoma.

PURPOSE: Cervical cancer is still one of the main causes of death in females. Conventional diagnostic tools such as colposcopy are still unsatisfactory, so accurate diagnostic tools for cervical diseases are needed. Therefore, the purpose of this study was to perform a clinical study to evaluate the value of microendoscopic imaging systems in the diagnosis of cervical precancerous lesions and cervical microinvasive carcinoma (MIC). METHODS: Totally 106 patients ranging in age from 23 to 67 years were recruited. All patients had abnormal thin-layer cytology (TCT) results (≥ low-grade squamous intraepithelial lesions) and high-risk human papillomavirus (HPV) positivity. Each patient was first subjected to ordinary colposcopy, followed by microendoscopy and biopsy. All results of the colposcopy and microendoscopy images were compared to the histopathological diagnosis. RESULTS: Characteristics of pathological blood vessels were easily distinguished by microendoscopy compared with ordinary colposcopy. The diagnostic agreement rate of microendoscopy with the pathological diagnosis was higher (95.3%) than that of ordinary colposcopy (37.7%) (weighted kappa = 0.863, P < .01). When diagnosing HSIL and more advanced disease, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the microendoscopic diagnosis were significantly higher than those of ordinary colposcopy (97.6 and 38.1%), (95.5 and 63.6%), (98.8 and 80.0%), (91.3 and 21.2%) and (97.7 and 43.4%), respectively. CONCLUSION: This study shows that microendoscopy has important value in the diagnosis of cervical lesions which can provide real-time diagnosis in vivo without staining, particularly for lesions that are not sensitive to acetic acid staining.

Peritoneal Recurrence of Squamous Cell Carcinoma in a Young Woman After Conization for Microinvasive Cervical Cancer.

Microinvasive squamous cell carcinoma of the cervix develops mainly in young women. As metastases rarely occur, cervical conization to preserve fertility is often performed. We report a case of peritoneal recurrence developed after conization. A 31-year-old nulligravid woman with microinvasive squamous cell carcinoma of the cervix was treated with laser conization. Pathology showed a stromal invasion of <1 mm and a longitudinal spread of 3 mm without lymphovascular space involvement. Forty-seven months after conization, a pelvic examination revealed a firm, immobile mass on the right side of the pelvis. Transvaginal ultrasonography and magnetic resonance imaging showed a 3.8-cm solid mass located right of the rectum and anterior to the sacrum. A fine-needle biopsy showed squamous cell carcinoma. The tumor was diagnosed as a metastasis of cervical carcinoma. After salvage concurrent chemoradiation, the patient was well and had no evidence of disease at 90 months after the treatment. In this case, tumor cells appear to spread through the endometrial cavity and the lumen of the fallopian tube.

Identification of cervical cancer stem cells using single-cell transcriptomes of normal cervix, cervical premalignant lesions, and cervical cancer.

BACKGROUND: Cervical cancer is the fourth leading cause of mortality among gynecological malignancies. However, the identification of cervical cancer stem cells remains unclear. METHODS: We performed single-cell mRNA sequencing on ∼122,400 cells from 20 cervical biopsies, including 5 healthy controls, 4 high-grade intraepithelial neoplasias, 5 microinvasive carcinomas of the cervix, and 6 invasive cervical squamous carcinomas. Bioinformatic results were validated by multiplex immunohistochemistry (mIHC) in cervical cancer tissue microarrays (TMA) (n = 85). FINDINGS: We identified cervical cancer stem cells and highlighted the functional changes in cervical stem cells during malignant transformation. The original non-malignant stem cell properties (characterized by high proliferation) gradually diminished, whereas the tumor stem cell properties (characterized by epithelial-mesenchymal transformation and invasion) were enhanced. The mIHC results of our TMA cohort confirmed the existence of stem-like cells and indicated that cluster correlated with neoplastic recurrence. Subsequently, we investigated malignant and immune cell heterogeneity in the cervical multicellular ecosystem across different disease stages. We observed global upregulation of interferon responses in the cervical microenvironment during lesion progression. INTERPRETATION: Our results provide more insights into cervical premalignant and malignant lesion microenvironments. FUNDING: This research was supported by the Guangdong Provincial Natural Science Foundation of China (2023A1515010382), Grant 2021YFC2700603 from the National Key Research & Development Program of China and the Hubei Provincial Natural Science Foundation of China (2022CFB174 and 2022CFB893).

Clinicopathological characteristics and prognosis of microinvasive breast cancer: A population-based analysis.

OBJECTIVES: Microinvasive breast cancer (MIBC) is a special type of breast cancer with a relatively low prevalence, of which the understanding remains controversial. In this article, we aimed to clarify the clinicopathological characteristics and prognosis of MIBC in the setting of different molecular subtypes and give feasible suggestions on clinical practice in MIBC. METHODS: This study utilized the data from Surveillance, Epidemiology, and End Results (SEER) database. Patients were divided into subgroups based on the molecular subtypes, of which the clinicopathological characteristics were further undergone comparative analyses. Kaplan-Meier method and Cox proportional hazard regression analysis were employed to determine the prognosis of the subtypes, and to explore the prognostic factors. Patients were randomly assigned in a 7:3 ratio to the training and validation cohorts. The independent risk variables were then adopted to generate a nomogram to predict the 3- and 5-year survival probability. RESULTS: A total of 4301 MIBC patients between 2010 and 2016 were obtained from the SEER database, which were subsequently separated into HR+/HER2- (n = 2598), HR+/HER2+ (n = 723), HR-/HER2+ (n = 633), and HR-/HER2- (n = 347) groups. The HR+/HER2+ group showed the best overall survival (OS) (81.28 months, 95% CI 80.45-82.11) compared with other groups (p = 0.0089). The application of radiotherapy in HR+/HER2- and HR+/HER2+ MIBC patients brought out additional survival benefit compared with those without radiotherapy (p < 0.0001 and p = 0.024, respectively). The prognosis among four subgroups with or without chemotherapy showed no statistical difference. Based on the curated nomogram, the high-score group exhibited a better OS compared with patients from the low-score group. CONCLUSIONS: Profound heterogeneity was detected among different molecular subtypes in MIBC patients, of which HR+/HER2+ subtype presented the best prognosis. For HR-positive MIBC patients, increasing survival benefits could be retrieved from radiotherapy. Chemotherapy was not recommended for patients with MIBC. Individual-based protocols were introduced based on the nomogram which warranted further validation.

Predictive factors of invasion in ductal carcinoma in situ diagnosed by core-needle biopsy.

OBJECTIVE: To identify clinical, radiological, and histopathological characteristics that could be predictive factors of microinvasive/invasive breast carcinoma in patients with diagnosis of ductal carcinoma in situ (DCIS) by core-needle biopsy. MATERIAL AND METHODS: This is a retrospective study conducted from 2006-2017, which included women ≥18 years of age with initial DCIS, and who were treated with surgery. Final diagnosis was divided in DCIS and microinvasive/invasive carcinoma. RESULTS: 334 patients were included: 193 (57.8%) with DCIS and 141 (42.2%) with microinvasive/invasive carcinoma (microinvasive 5.1%, invasive 37.1%). Lymph node metastasis occurred in 16.3%. Differences between DCIS and microinvasive/invasive groups included the presence of palpable nodule (36.7% vs. 63.2%), radiological nodule (29% vs. 51%), bigger radiological-tumor size (1.2 cm vs. 1.7 cm), and larger microcalcification extension (2.5 cm vs. 3.1 cm), all of these variables p ≤0.05. Hormonal receptors and HER2 expression were similar. After logistic regression analysis, predictive factor of invasion was the presence of palpable nodule (OR = 4.072, 95%CI = 2.520-6.582, p <0.001) and radiological multicentric disease (OR = 1.677, 95%CI = 1.036-2.716, p = 0.035). CONCLUSIONS: In patients with DCIS, palpable nodule, and radiological multicentric disease, upgrade to microinvasive/invasive is high, and sentinel lymph node is recommended.

OBJETIVO: Identificar características clínicas, radiológicas e histopatológicas como factores predictivos de carcinoma mamario microinvasor/invasor en pacientes con Carcinoma Ductal In Situ (CDIS) diagnosticado mediante aguja de corte. MATERIAL Y MÉTODOS: Estudio retrospectivo de 2006­2017, en mujeres ≥18 años con CDIS diagnosticado con aguja de corte y tratadas con cirugía. Los diagnósticos finales fueron CDIS y carcinoma microinvasor/invasor. RESULTADOS: Se incluyeron 334 pacientes, 193 (57.8%) con CDIS y 141 (42.2%) con carcinoma microinvasor/invasor (microinvasor 5.1%, invasor 37.1%). Hubo 16.3% casos con afección ganglionar. Las diferencias entre el grupo de CDIS y carcinoma microinvasor/invasor fue la presencia de tumor palpable (36.7% vs. 63.2%), nódulo visto por imagen (29% vs. 51%), tumores más grandes (1.2 cm vs. 1.7 cm), y mayor extensión de microcalcificaciones (2.5 cm vs. 3.1 cm), estas variables con p ≤0.05. Los receptores hormonales y HER2 fueron similares. En el análisis de regresión logística, los factores predictivos de invasión fueron tumor palpable (OR = 4.072, IC95% = 2.520­6.582, p <0.001) y multicentricidad radiológica (OR = 1.677, IC95% = 1.036­2.716, p = 0.035). CONCLUSIONES: En CDIS, tumor palpable y enfermedad multicéntrica radiológica, el escalamiento a carcinoma microinvasor/invasor es alto y es recomendable realizar ganglio centinela.

Significance of HER2 in Microinvasive Breast Carcinoma.

OBJECTIVES: We compared the clinicopathologic features, clinical management, and outcomes of human epidermal growth factor receptor 2 (HER2)-expressing and nonexpressing microinvasive breast carcinomas (MiBC) to explore the significance of HER2 in MiBC. METHODS: Clinicopathologic and follow-up information of cases with final diagnosis of MiBC with known HER2 status between 2007 and 2019 were analyzed. RESULTS: Nineteen (41.3%) HER2-positive (HER2+) and 27 (58.7%) HER2-negative (HER2-) MiBCs were identified. HER2 positivity was likely to be associated with high nuclear grade, presence of tumor-infiltrating lymphocytes, hormonal receptor negativity, and increased Ki-67 in both microinvasive and associated in situ carcinomas. Nodal metastases were found in 2 ER+/HER2- cases (5.3%). One HER2+ case was found to have isolated tumor cells in the axillary node. The majority of patients with HER2+ MiBCs (76.5%) did not receive HER2-targeted therapy. All patients with available follow-up were alive without recurrence or distant metastasis, with a median follow-up of 38 months. CONCLUSIONS: Similar to the larger size of invasive breast carcinomas, HER2 positivity is associated with high-grade morphologic features in MiBCs. However, HER2 overexpression in MiBCs does not appear to be associated with nodal metastasis or worse outcome in our study cohort. The role of HER2-targeted therapy in this clinical setting merits additional study.

Molecular alterations differentiate microinvasive carcinoma from ductal carcinoma in situ and invasive breast carcinoma: retrospective analysis of a large single-center series.

Microinvasive carcinoma (MIC) of the breast is a rare lesion. The clinicopathologic features and biologic behavior of MIC are unclear. Whether MIC is a distinct entity or an interim stage in the progression from ductal carcinoma in situ (DCIS) to invasive breast carcinoma (IBC) remains to be determined. A retrospective review of clinicopathologic features and analysis of the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), and Ki-67 in patients with MIC (90 cases), DCIS (268 cases) and IBC (1504 cases) was performed. Most MICs (93.3%) exhibited an intermediate to high nuclear grade, and this proportion was larger than that of DCIS (62.7%, P < 0.001) or IBC (85.4%, P = 0.036). The incidence of sentinel lymph node metastasis in MIC (12.5%) was higher than that of DCIS (1.6%, P < 0.001), but much lower than that of IBC (39.7%, P < 0.001). MICs had higher expression of HER-2 and lower expression of ER and PR compared to DCIS and IBC; and MIC was more likely to present with a HER-2+ subtype. Furthermore, DCIS exhibited greater HER-2 overexpression or gene amplification (P < 0.001) levels and lower proliferation index of Ki-67 (P < 0.001) compared to IBC. Our results suggest that the clinicopathologic and molecular phenotype of MIC are different from DCIS and IBC. Thus, MIC may be a distinct entity rather than an interim stage in the progression from DCIS to IBC. The prognosis of MIC and the biologic behavior of this uncommon subset need to be further explored.

Treatment Outcomes of Patients With Cervical Intraepithelial Neoplasia or Invasive Carcinoma Who Underwent Loop Electrosurgical Excision Procedure.

BACKGROUND: This study aimed to evaluate the treatment outcomes of cervical intraepithelial neoplasia (CIN) or cancer patients who underwent loop electrosurgical excision procedure (LEEP) in terms of primary outcome and factors associated with persistence/recurrence. METHODS: Patients with CIN or cancer who underwent LEEP from January 2007 to December 2015 were reviewed. Data collected were age, parity, menopausal status, human immunodeficiency virus (HIV) infection, smoking, cervical cytology, histopathology from cervical biopsy and LEEP including margin status, final histopathology, and follow-up data. RESULTS: The mean age of 385 patients was 41.9 ± 10.8 years (range 18 - 79 years). Majority were multiparous (81.6%) and premenopausal (78.2%). There were 15.3% of patients with HIV infection. The most common cervical cytology was high-grade squamous cell intraepithelial lesion (HSIL, 44.1%), followed by atypical squamous cells of undetermined significance (ACS-US, 21%). Minor complications of bleeding or infection from LEEP were encountered in 7.3%. Among 153 patients (39.7%) who had positive margin(s), 43 underwent second LEEP, whereas 76 had hysterectomy. From all patients, 47 had failure after treatment (12.2%), being either persistence (30 patients; 7.8%) or recurrence (17 patients; 4.4%). Factors associated with persistence or recurrence by multivariate analysis were age ≥ 55 years old, HIV infection, final diagnosis of invasive cancer, and positive endocervical margin or both ecto- and endo- cervical margins. CONCLUSIONS: LEEP had low rate of persistence/recurrence. Age ≥ 55 years old, HIV infection, final diagnosis of cancer, and positive endocervical or both endo- and ecto- surgical margin(s) were significantly associated with persistent or recurrent diseases.

Loop electrosurgical excision procedure combined with cold coagulation for cervical intraepithelial neoplasia and adenocarcinoma in-situ: a feasible treatment with a low risk of residual/recurrent disease.

OBJECTIVE: This study was performed to evaluate the significance of positive resection margins (RMs) with the loop electrosurgical excision procedure combined with cold coagulation (LEEP with CC) as a definitive treatment for patients with cervical intraepithelial neoplasia (CIN) and adenocarcinoma in-situ. METHODS: We retrospectively reviewed 467 patients who underwent LEEP with CC. A right-angled triangular loop in a single pass followed by a CC (120 °C) to the cone bed for 10 to 20 s was used. Pathology reports and clinical data were obtained and evaluated. RESULTS: Histopathology evaluation of LEEP tissue samples revealed the presence of CIN 1 in 69, CIN 2/3 in 366, AIS in 5 and invasive carcinoma in 16 (microinvasive squamous cell carcinoma (SCC) and invasive SCC, 13 and 3) patients. Margins were positive in 66 (14.5%) cases: 0 in CIN 1, 54 in CIN 2/3 (12.4%), 1 in AIS (20.0%) and 11 in microinvasive/invasive SCC (68.8%). Although 54 CIN2/3 patients with positive RMs did not undergo additional treatment, 1 of these (1.9%) was confirmed to have residual CIN3 at the first follow-up. Two of 8 (25.0%) microinvasive SCC patients with positive RMs were confirmed to have residual diseases (1 microinvasive SCC and 1 invasive SCC) after hysterectomy. Four out of 360 (1 positive RM, 3 negative RM) CIN cases recurred during the study period. CONCLUSIONS: These results suggest that CIN patients with positive RMs after LEEP with CC may be followed up without additional treatment.

Histopathological alterations in the prostates of Mongolian gerbils exposed to a high-fat diet and di-n-butyl phthalate individually or in combination.

Both high-fat diet and exposure to endocrine-disrupting chemicals have been implicated in susceptibility to pathological prostate lesions, but the consequences of combining the two have not yet been examined. We evaluated the effects of gestational and postnatal exposure to a high-fat diet (20% fat) and low doses of di-n-butyl phthalate (DBP; 5mg/kg/day), individually or in combination, on the tissue response and incidence of pathological lesions in the ventral prostate of adult gerbils. Continuous intake of a high-fat diet caused dyslipidemia, hypertrophy, and promoted the development of inflammatory, premalignant and malignant prostate lesions, even in the absence of obesity. Life-time DBP exposure was obesogenic and dyslipidemic and increased the incidence of premalignant prostate lesions. Combined exposure to DBP and a high-fat diet also caused prostate hypertrophy, but the effects were less severe than those of individual treatments; combined exposure neither induced an inflammatory response nor altered serum lipid content.

Microinvasive lobular carcinoma arising in a fibroadenoma.

A 51-year-old woman had a 35 mm circumscribed calcified lesion identified on screening mammography, designated R4. Excision showed a fibroadenoma with multiple foci of lobular neoplasia (atypical lobular hyperplasia and classical lobular carcinoma in situ [LCIS]). A focus of microinvasive lobular carcinoma (MILC) was also present, confirmed on immunohistochemistry. The MILC cells were ER positive, Her-2-negative, and e-cadherin negative. Microinvasive carcinoma, defined as "invasive carcinoma with no focus measuring >1 mm" (TNM UICC 7th edition) is usually encountered in ductal carcinoma in situ but may occur with classical, florid, or pleomorphic LCIS. In one series MILC constituted 0.4% of all invasive lobular carcinomas and was present in 0.4% of all LCIS. MILC is a histologically subtle lesion, the identification of which lends further weight to the concept of lobular neoplasia as a precursor lesion. MILC has been observed in hamartoma but, to our knowledge, has not previously been reported in fibroadenoma.