sLe^(x) expression in invasive micropapillary breast carcinoma is associated with poor prognosis and can be combined with MUC1/EMA as a supplementary diagnostic indicator

Objective: Mucin 1(MUC1/EMA) and sialyl Lewis X(sLe^(x)) indicate polarity reversal in invasive micropapillary carcinoma(IMPC). The purpose of this study was to evaluate the expression of MUC1/EMA and sLe^(x) and to assess their diagnostic and prognostic value in patients with IMPC.Methods: The expression of sLe^(x) and MUC1/EMA in 100 patients with IMPC and a control group of 89 patients with invasive ductal carcinoma not otherwise specified(IDC-NOS) were analyzed with IHC. Fresh tumor tissues were collected from patients with IMPC or IDC-NOS for primary culture and immunofluorescence analysis.Results: The rate of nodal metastasis was higher in patients with IMPC than those with IDC-NOS, and IMPC cells tended to express more sLe^(x) and MUC1/EMA in the cytomembranes(the stroma-facing surfaces of the micropapillary clusters) than IDC-NOS cells. In IMPC, high cytomembrane expression of sLe^(x), but not MUC1/EMA, indicated poor prognosis. In addition, among the 100 patients with IMPC, 10 patients had sLe^(x)+/EMA-expression patterns, and 8 patients had sLe^(x)-/EMA+ expression patterns. The primary IMPC cells were suspended, non-adherent tumor cell clusters, whereas the primary IDC cells were adherent tumor cells. Immunofluorescence analysis showed that MUC1/EMA and sLe^(x) were co-expressed on the cytomembranes in IMPC cell clusters and in the cytoplasm in IDC-NOS cells.Conclusions: sLe^(x) can be used as a prognostic indicator and can be combined with MUC1/EMA as a complementary diagnostic indicator to avoid missed IMPC diagnosis.

Invasive micropapillary carcinoma:A distinct type of adenocarcinomas in the gastrointestinal tract

Invasive micropapillary carcinoma (IMPC) is a rare histological type of tumor, first described in invasive ductal breast cancer, than in malignancies in other organs such as lungs, urinary bladder, ovaries or salivary glands. Recent literature data shows that this histological lesion has also been found in cancers of the gastrointestinal system. The micropapillary components are clusters of neoplastic cells that closely adhere to each other and are located in distinct empty spaces. Moreover, clusters of neoplastic cells do not have a fibrous-vascular core. The IMPC cells show reverse polarity resulting in typical ‘’inside-out’’ structures that determines secretary properties, disturbs adhesion and conditions grade of malignancy in gastrointestinal (GI) tract. Invasive micropapillary carcinoma in this location is associated with metastases to local lymph nodes and lymphovascular invasion. IMPC can be a prognostic factor for patients with cancers of the stomach, pancreas and with colorectal cancer since it is related with disease-free and overall survival. The purpose of this review is to present the characterization of invasive micropapillary carcinoma in colon, rectum, stomach and others site of GI tract, and to determine the immunohistological indentification of IMPC in those localization.

Phagocytosis(cannibalism) of apoptotic neutrophils by tumor cells in gastric micropapillary carcinomas

AIM:To identify those with a micropapillary pattern,ascertain relative frequency and document clinicopathological characteristics by reviewing gastric carcinomas.METHODS:One hundred and fifty-one patients diagnosed with gastric cancer who underwent gastrectomy were retrospectively studied and the presence of a regional invasive micropapillary component was evaluated by light microscopy.All available hematoxylin-eosin(HE)-stained slides were histologically reviewed and 5 tumors were selected as putative micropapillary carcinoma when cancer cell clusters without a vascular core within empty lymphatic-like space comprised at least5%of the tumor.Tumor tissues from these 5 invasive gastric carcinomas were immunostained using an antimucin 1(MUC1)antibody(clone MA695)to detect the characteristic inside-out pattern and with D2-40antibody to determine the presence of intratumoral lymph vessels.Detection of intraepithelial neutrophil apoptosis was evaluated in consecutive histological tissue sections by three independent methods,namely light microscopy with HE staining,the conventional terminal deoxynucleotidyl transferase-mediated d UTP-biotin nick end-labeling(TUNEL)method and immunohistochemistry for activated caspase-3(clone C92-605).RESULTS:Among 151 gastric cancers resected for cure,5(3.3%)were adenocarcinomas with a micropapillary component.Four of the patients died of disease from 6 to 23 mo and one patient was alive with metastases at 9 mo.All patients had advanced-stage cancer(≥p T2)and lymph node metastasis.Positive MUC1 immunostaining on the stroma-facing surface(inside-out pattern)of the carcinomatous cluster cells,together with negative immunostaining for D2-40 in the cells limiting lymphatic-like spaces,confirmed the true micropapillary pattern in these gastric neoplasms.In all five cases,several micropapillae were infiltrated by neutrophils.HE staining,TUNEL assay and immunostaining for caspase-3 demonstrated apoptoticneutrophils within cytoplasmic vacuoles of tumor cells.These data suggest phagocytosis(cannibalism)of apoptotic neutrophils by micropapillary tumor cells.Tumor cell cannibalism is usually found in aggressive tumors with anaplastic morphology.Our data extend these observations to gastric micropapillary carcinoma:a tumor histotype analogously characterized by aggressive behavior and poor prognosis.The results are of interest because they raise the intriguing possibility that neutrophil cannibalism by tumor cells may be one of the mechanisms favoring tumor growth in gastric micropapillary carcinomas.CONCLUSION:This is the first study showing phagocytosis(cannibalism)of apoptotic neutrophils by tumor cells in gastric micropapillary carcinomas.

Rare histological subtype of invasive micropapillary carcinoma in the ampulla of Vater: A case report

BACKGROUND Carcinoma of the ampulla of Vater is an uncommon ampullo-pancreatobiliary neoplasm,and the most common histological type is adenocarcinoma with a tubular growth pattern.Invasive micropapillary carcinoma(IMPC)is an aggressive variant of adenocarcinoma in several organs that is associated with lymph node metastasis and poor prognosis.IMPC was first described as a histological subtype of breast cancer;however,IMPC of the ampulla of Vater is extremely rare,with only three articles reported in the English literature.CASE SUMMARY We have reported a case of IMPC of the ampulla of Vater in an 80-year-old man.Microscopically,the surface area of the carcinoma was composed of tubulopapillary structures mimicking intra-ampullary papillary-tubular neoplasm,and the deep invasive front area exhibited a pattern of IMPC.The carcinoma showed lymphatic invasion and extensive lymph node metastasis.The immunohistochemical study revealed mixed intestinal and gastric/pancreatobiliary phenotypes.CONCLUSION This rare subtype tumor in the ampulla of Vater showed a histologically mixed phenotype and exhibited aggressive behavior.

MTDH Expression in Invasive Micropapillary Carcinoma of the Breast

OBJECTIVE To clarify the expression of MTDH in invasive micropapillary carcinoma of the breast （IMPC） and analyze the relationship between MTDH expression and clinicalpathologic parameters of the IMPC patietns.

Relationship between Lymphatic Vessel Density and Lymph Node Metastasis of Invasive Micropapillary Carcinoma of the Breast

OBJECTIVE To investigate the relationship between lymphatic vessel density and lymph node metastasis of invasive micropapillary carcinoma (IMPC) of the breast. METHODS The immunohistochemical study for vascular endothelial growth factor-c (VEGF-C), VEGF Receptor-3 (VEGFR-3) and lymphatic vessel density of 51 cases of IMPC were performed, and lymph node metastases were examined by microscopic analysis of these cases. RESULTS In IMPC, VEGF-C was expressed in the cytoplasm and/or on the membrane of the tumor cells, and the expression of VEGF-C showed a positive correlation with lymph node metastasis (P<0.01). Lymphatic vessel density was determined by the number of micro-lymphatic vessels with VEGFR-3 positive staining. Lymphatic vessel density was positively correlated with VEGF-C expression (P<0.01) and lymph node metastasis (P<0.01). The percentage of IMPC in the tumor was not associated with the incidence of lymph node metastasis. The metastatic foci in lymph nodes were either pure or predominant micropapillary carcinoma. CONCLUSION The results suggested that VEGF-C overexpression stimulated tumor lymphangiogenesis, and the increased lymphatic vessel density may be the key factor that influenced lymph node metastasis of IMPC.

Inverted Apical CD24 and Weak EZH2 Expressions Are Phenotypic Characteristics of Pure Invasive Micropapillary Carcinoma of the Breast

Invasive micropapillary carcinomas (IMPC) of the breast account for less than 2% of all breast cancers and have been recently described as luminal B carcinomas. CD24, CD44, ALDH1 and EZH2 are commonly used as stem-cell markers that display differential expression as a function of stage and molecular type, but their pattern of expression according to this rare histological type remains poorly defined and unknown for EZH2. We assessed expression of these markers in a series of 28 micropapillary breast carcinomas and compared the results with those obtained in a series of luminal A (27 cases) and B (34 cases) invasive carcinomas not otherwise specified (IC-NST). CD24 and CD44 were expressed in most cases. However, CD24 was expressed at the inverted apical membrane in 85% of invasive micropapillary carcinoma and at the apical pole of gland-forming cells in 45% of luminal A (p-val = 6.8 × 10-4) and 13% of luminal B cases (p-val = 1.1 × 10-7). ALDH1 was expressed in the stroma in most tumors, but in only 25%, 11% and 15% in epithelial cells of IMPC, luminal A and B IC-NST, respectively. Nuclear expression of EZH2 was not observed in luminal A tumors, and was detected in 35% (12/34) of luminal B carcinomas (p-val = 6.1 × 10-3) and only 4% (1/28) of invasive micropapillary carcinomas. This series shows that invasive micropapillary carcinomas harbor a CD24-positive inverted apical pole associated with weak EZH2 expression, phenotypical characteristics that distinguish this entity from other luminal carcinomas.

Effect of Micropapillary Pattern and Spread through Air Space in Patients with Lung Adenocarcinoma ≤ 2 cm

Objective: To analyze the relationship between micropapillary pattern (MIP) and tumor spread through air space (STAS) and postoperative survival rate in patients with lung adenocarcinoma ≤ 2 cm. Methods: Retrospective analyses were performed on clinical data of 575 patients with lung adenocarcinoma ≤ 2 cm, which were resected from 2009 to 2011. We analyzed the pathological findings on the resected specimens, with special reference to the presence/absence MIP and STAS, which have been reported to be a marker of poor prognosis of lung adenocarcinoma. Patients were divided into three according to the presence/absence of MIP and STAS: low-risk (MIP- STAS-), medium-risk (either MIP or STAS + (one plus)) and high-risk group (+/+: double plus). Endpoint was postoperative survival rate, which was compared among three groups. Results: There was no statistical difference in age, sex, and serum CEA level among three groups. In lobectomized patients, there was no statistical difference in prognosis among three groups;however, in sub-lobectomy group, patients with double + (+/+ for MIP and STAS) showed a lower survival rate than others (P < 0.001). Conclusion: The presence of MIP and STAS reduced the survival rate in sub-lobectomized patients.

Clinical Value Analysis of Ultrasonography and MRI in Diagnosis of Invasive Micropapillary Carcinoma of Breast

Objective:To investigate the diagnostic value of invasive micropapillary carcinoma(IMPC)by ultrasonography and MRI.Method:63 female patients with IMPC were selected,all of which were confirmed by pathological examination,and were assigned to the IMPC group.In the same period,40 patients with invasive ductal carcinoma(IDC group)were selected for diagnostic efficacy control.The efficacy indexes of accuracy,sensitivity,specificity,positive prediction rate and negative prediction rate were 73.0%,65.9%,89.5%,93.5%,46.9%,respectively.The efficiency indexes of accuracy,sensitivity,specificity,positive prediction rate and negative prediction rate of ultrasound combined with breast MRI were 93.6%,93.2%,94.7%,97.6%,85.7%.Ultrasonography combined with MRI has more application value in the diagnosis of IMPC.

Prognosis of lymphotropic invasive micropapillary breast carcinoma analyzed by using data from the National Cancer Database

Background:Invasive micropapillary carcinoma(IMPC)is an uncommon subtype of breast cancer.Previous studies of this subtype demonstrated a higher propensity for lymph node metastases as compared with invasive ductal carci-noma(IDC).The purpose of the present study was to determine the clinical characteristics,outcomes,and propensity for lymph node metastasis of patients with IMPC of the breast recorded in the National Cancer Database(NCDB).Methods:Records of patients with IMPC diagnosed between 2004 and 2014 were retrieved from the NCDB.Log-rank test was performed to evaluate associations of clinical characteristics with overall survival(OS).Cox proportional hazards model was used to determine variables associated with OS.Results:Overall,2660 patients with IMPC met the selection criteria;the 5-year OS rate was 87.5%and 24.9%of patients had nodal involvement at presentation.Patients with≥4 positive lymph nodes had shorter OS than node-negative patients,whereas patients with 1-3 positive nodes had similar OS to node-negative patients.Age<65 years,receipt of radiotherapy,and estrogen receptor positivity were also associated with prolonged OS.The benefit of radiotherapy was limited to IMPC patients undergoing lumpectomy;there was no benefit for the patients undergoing mastectomy(regardless of nodal positivity/negativity).Conclusions:Favorable prognostic factors of IMPC patients included age<65 years,<4 positive lymph nodes,receipt of radiotherapy,and estrogen receptor positivity.The results presented herein suggest a survival benefit asso-ciated with radiotherapy in IMPC treatment,though this may be limited to the patients treated with lumpectomy.

Study on the Influencing Factors of Cervical Lymph Node Metastasis in Papillary Thyroid Microcarcinoma

Objective:To investigate the influencing factors of the cervical lymph node metastasis in papillary thyroid microcarcinoma(PTMC)and to provide a theoretical basis for cervical lymph node dissection.Methods:A total of 80 PTMC patients treated in the Department of Breast and Thyroid Surgery of our Hospital from January 2017 to January 2018 were selected in the study.All the patients accepted the first surgical treatment and were confirmed by pathology.The clinical data of all PTMC patients were retrospectively analyzed,and the related factors such as gender,age,number of primary lesions,tumor diameter and extrathyroidal invasions were analyzed.The factors that actually affected the lymph node metastasis of PTMC patients were explored.Results:All patients underwent prophylactic central lymph node dissection.Lymph node metastasis occurred in 26 patients in the central region and in 13 patients in the lateral neck region.The rate of lymph node metastasis in the central region of men was 41.18%,and the rate of lymph node metastasis in the lateral neck region was 23.53%,which were significantly higher than that of women's 30.16%and 14.29%.The differences were statistically significant(P<0.05).The regional metastasis rate of the patients of≤45 years was 45.83%,and the lateral neck region metastasis rate was 20.83%,which were significantly higher than those of patients>45 years old(12.50%,9.38%)and the differences were statistically significant(P<0.05).The lymph node metastasis rate in the central region and in the lateral neck region of tumor diameter<0.5 cm were 27.27%and 9.09%respectively,which were significantly lower than those of the tumor diameter 0.5-1.0 cm(38.89%,25.00%)(P<0.05).The rate of lymph node metastasis in the central region of single focus was 20.37%,which was significantly lower than that of 57.69%in the multifocal lesions;the rate of lymph node metastasis in the cervical region of the single lesion was 11.11%,which was significantly lower than 26.92%in the multifocal area;the differences were statistically significant(P<0.05).The metastasis rate of the patients with extrathyroidal invasions in the central area was 60.00%,which is significantly higher than that without extrathyroidal invasions(30.67%).About the tumor neck invasion of the lateral neck region,the lymph node metastasis rate of the patients with extrathyroidal invasions was 40.00%,which was significantly higher than that without extrathyroidal invasions(14.67%).The differences were statistically significant(P<0.05).Logistic regression analysis showed that gender and tumor size were independent influencing factors of lymph node metastasis in the central and lateral neck regions(P<0.05).Conclusion:Young,male,multifocal,tumor diameter 0.5-1.0 cm and extrathyroidal invasions are risk factors for cervical lymph node metastasis in patients with PTMC.Gender and tumor size are independent factors affecting central/lateral cervical lymph node metastasis in PTMC patients.