Micropapillary Carcinoma Component Research Articles

Investigation of the genome-wide signatures underlying the micropapillary carcinoma components in colorectal cancers

Investigation of the genome-wide signatures underlying the micropapillary carcinoma components in colorectal cancers

A Case of Early Colorectal Cancer with Invasive Micropapillary Carcinoma Component with Peritoneal Dissemination Recurrence

A Case of Early Colorectal Cancer with Invasive Micropapillary Carcinoma Component with Peritoneal Dissemination Recurrence

Clinicopathological characteristics of pancreatic ductal adenocarcinoma with invasive micropapillary carcinoma component with emphasis on the usefulness of PKCζ immunostaining for detection of reverse polarity.

Invasive micropapillary carcinoma (IMPC) is a rare distinct histopathological subtype, characterized by the presence of carcinoma cells displaying reverse polarity. Only limited clinicopathological information is available regarding pancreatic IMPC. The aim of the present study was to clarify the clinicopathological features of pancreatic IMPC and the usefulness of protein kinase C (PKC)ζ immunostaining for the detection of reverse polarity. We reviewed 242 consecutive surgically resected specimens of pancreatic ductal adenocarcinoma and selected samples with an IMPC component. Clinicopathological characteristics were compared between the IMPC and non-IMPC groups. Immunohistochemical staining for PKCζ was performed using an autostainer. In total, 14 cases had an IMPC component (5.8%). The extent of IMPC component ranged from 5 to 20%. There were no significant differences in tumor location, T category, lymph node metastatic status, preoperative carbohydrate antigen 19-9 level, resection status and overall survival between the IMPC and non-IMPC groups. Immunostaining for PKCζ clearly showed reverse polarity of the neoplastic cells of IMPC. Although previous reports have shown that the presence of an IMPC component (>20% of the tumor) indicated poor prognosis, the present study demonstrated that presence of IMPC <20% did not suggest a worse prognosis.

A male with primary accessory breast carcinoma in an axilla is strongly suspected of having hereditary breast cancer

We herein report on a male with primary accessory breast cancer in an axilla. A 75-year-old man first noticed a subcutaneous nodule about 2 cm in diameter in the area of his right axilla. The patient underwent extirpation of the mass in a public hospital. Histological examination revealed invasive breast carcinoma of no special type associated with mucinous carcinoma, invasive micropapillary carcinoma and intraductal components. Immunohistochemical analysis showed that the tumor cells were positive for Gross cystic disease fluid protein (GCDFP)-15, mammaglobin and GATA3. Staining for estrogen receptor (ER) and progesterone receptor (PR) was positive, and human epidermal growth factor receptor 2 (HER2) was negative. The Ki67 labeling index (LI) was 33.6%. Imaging revealed no evidence of a primary tumor in any other organ or in the bilateral mammary gland. We performed radical resection of the right axilla, including the scar, and axillary lymph node dissection. The final pathological examination of the surgical specimen showed normal mammary gland tissue that was not connected to the proper mammary gland, and no residual cancer or metastatic lymph nodes. Based on our clinical and pathological findings, this tumor was diagnosed as breast cancer originating from the accessory mammary gland in the right axilla. After surgery, tamoxifen was administered as adjuvant therapy. Since the surgery, 2 years ago, there has been no evidence of recurrence. Hereditary Breast and Ovarian Cancer syndrome was suspected in this case because the patient was a male with breast cancer, and he had two first-degree relatives with breast cancer. This patient had no BRCA mutations on genetic testing. Nonetheless, in cases of male breast cancer, it is necessary to obtain genetic information due to the possibility of hereditary breast cancer, including cancers associated with BRCA gene mutation.

Intense basolateral membrane staining indicates HER2 positivity in invasive micropapillary breast carcinoma.

Invasive micropapillary carcinoma is characterized by the inside-out growth of tumor clusters and displays incomplete membrane immunostaining of HER2. According to the 2018 American Society of Clinical Oncology and the College of American Pathologists (ASCO/CAP) HER2-testing recommendation, moderate to intense but incomplete staining could be scored as immunohistochemical 2+. Furthermore, the criteria of immunohistochemical 3+ for this staining pattern are not mentioned. One hundred and forty-seven cases of invasive micropapillary carcinoma with moderate-to-intense HER2 immunostaining were enrolled. Invasive micropapillary carcinoma components of all cases were scored as immunohistochemical 2+ based on the 2018 ASCO/CAP recommendation. The invasive micropapillary carcinoma component varied from 10% to 100% (mean, 80%). Invasive micropapillary carcinoma components of all 147 tumors exhibited reversed polarity and incomplete basolateral HER2 membrane staining. One hundred and seventeen of the tumors (80%, 117/147) had moderate staining, and 38 (32%, 38/117) showed HER2 gene amplification by fluorescence in-situ hybridization. HER2 gene was amplified in all the remaining 30 tumors (20%, 30/147) that exhibited intense basolateral membrane staining. Besides, average HER2 signals per cell and ratio of HER2/CEP17 were significantly higher in the intense-staining tumors compared with the moderate-staining tumors (p < 0.0001). Follow-up data were available for 140 patients. None of the patients were died. The follow-up time ranged from 1 month to 99 months (median, 57 months). Thirteen (9%, 13/140) patients exhibited disease progression (recurrence or metastasis). HER2 gene amplification was correlated inversely with estrogen receptor (p = 0.000) and progesterone receptor (p = 0.000) expression, and positively with histological grade (p = 0.003) and disease progression (p = 0.000). Invasive micropapillary carcinoma with intense clear linear basolateral membrane immunostaining indicates HER2 positivity, even if the staining is incomplete. They should be classified as immunohistochemical 3+ rather than immunohistochemical 2+, which would avoid further fluorescence in-situ hybridization-testing procedure and greatly save the related time, labor, and financial costs. Ultimately, ensure all patients with HER2 gene amplification obtain effective targeted therapy in time.

A Case of Early Sigmoid Colon Cancer with Micropapillary Carcinoma Component with Lymph Node Metastasis

A Case of Early Sigmoid Colon Cancer with Micropapillary Carcinoma Component with Lymph Node Metastasis

Three Cases of Gastric Intramucosal Adenocarcinoma with Invasive Micropapillary Carcinoma Component

Three Cases of Gastric Intramucosal Adenocarcinoma with Invasive Micropapillary Carcinoma Component

Gastric mucinous carcinoma with micropapillary carcinoma component: Case report of tumor morphology not previously described in stomach

Micropapillary (MP) carcinoma is an uncommon tumor with a distinct histologic pattern. Although micropapillary carcinoma has been reported in the stomach, the concurrence of mucinous carcinoma and micropapillary carcinoma has not been reported to-date. A 69-year-old gentleman who presented with anemia was found at endoscopy to have a 1.7 cm gastric ulcer which was biopsied and subsequently underwent a partial gastrectomy. There was an ulcerated moderately differentiated adenocarcinoma displaying a micropapillary component within a mucinous adenocarcinoma component and a metastatic MP carcinoma in 1 of 18 lymph nodes. The tumor was immunoreactive for EMA, MUC2, MUC5AC, MUC6, CDX2, and p53 in both mucinous and mucinous-MP carcinoma areas; and negative for CK7, CK20, CA-125, synaptophysin, chromogranin, PD-L1, MMR proteins, and EBV. To the best of our knowledge, this is the first reported case of MP gastric carcinoma in association with mucinous carcinoma.

Invasive micropapillary carcinoma component is an independent prognosticator of poorer survival in Stage III colorectal cancer patients.

Invasive micropapillary carcinoma (IMPC) is an aggressive variant of adenocarcinoma found in several organs. Recent studies showed that IMPC in colorectal cancer leads to poorer prognosis than conventional colorectal cancer; however, the influence of IMPC on outcomes remains unclear. The present study aimed to identify the clinicopathological characteristics of colorectal cancers with IMPCs, and to evaluate the prognostic significance of IMPCs per se. We retrospectively analyzed data from 837 patients with colorectal cancer who underwent surgical treatment. We compared the clinicopathological characteristics and survival outcomes of colorectal cancer patients with IMPCs to those without. Among 837 patients, 130 (16%) had an IMPC component, including 0 (0%) of 18, 9 (4.2%) of 215, 34 (13%) of 254, 59 (24%) of 249 and 28 (27%) of 101 patients with TNM Stages 0, I, II, III and IV, respectively. The 3-year disease-free survival (DFS) rates were significantly worse for Stage III patients with IMPC than for those without (55.3% vs. 78.7% respectively, P < 0.001), but not in patients with other stages. Multivariate analyses of patients with Stage III colorectal cancer found IMPC to be associated with significantly worse DFS (P = 0.026), as were high CEA levels, tumor budding and TNM staging. IMPC was only significantly associated with tumor invasion (P = 0.045) and venous invasion (P = 0.045) in Stage III tumors. Identifying IMPC components in Stage III colorectal cancer is crucial, as their presence is significantly associated with poorer survival.

Colon cancer with micropapillary carcinoma component: a clinopathologic study of 9 cases.

Recently, colon cancer with micropapillary pattern (MPP) has been identified. MPP is defined as tight tufts surrounded by cleft-like space and lacking true fibrovascular cores and showing reverse polarity. In this article, we studied nine cases of colon cancer with MPP. MPP usually accounted for a minor component in total tumour volume, which ranged from 3 to 40% with a mean percentage of 19.2%. Associated histological subtype showed moderately differentiated tubular adenocarcinoma in all cases. The reverse polarity of villin (9/9, diffuse) in MPP component was superior to that of CA125 (5/9, focal) or CD10 (5/9, diffuse 2/9, focal 3/9). In clinicopathological indicators such as sex, tumour location, tumour depth, lymphovascular invasion, lymph node metastasis, or pathological stage and clinical behaviour, there was statistically no difference between the MPP group and the non-MPP group of the colon. In conclusion, colon cancer with MPP is characterised by frequent association with moderately differentiated tubular adenocarcinoma as a minor component. Villin immunohistochemistry is useful in the detection of reverse polarity of MPP of colon cancer.

Practical Points in Gastric Pathology.

-The diagnosis of gastric epithelial lesions is difficult in clinical practice, even with the recent developments and advances in endoscopic modalities, owing to the diverse morphologic features of the lesions, lack of standardized diagnostic criteria, and the high intraobserver and interobserver variabilities in the nonneoplastic (regenerative)-neoplastic spectrum. -To provide an overview of the current concepts and unresolved issues surrounding the diagnosis of diseases in the nonneoplastic-neoplastic spectrum, and to discuss some noteworthy properties and histologic features of gastric epithelial lesions. -A comprehensive assessment of the medical literature on gastric epithelial lesions was performed; we also interjected our own experiences into the discussion. Sources included original studies, review articles, and textbooks related to the field. -Our literature review revealed that clear cell changes and micropapillary carcinoma components in gastric carcinomas are associated with poor clinical outcomes and should hence be included in pathologic reports. Moreover, we suggest a stepwise biopsy-endoscopic resection modality for the diagnosis of borderline neoplasia-nonneoplasia cases.

Tu1822 Clinicopathological Characterization of Colorectal Cancer With Invasive Micropapillary Carcinoma Component

Tu1822 Clinicopathological Characterization of Colorectal Cancer With Invasive Micropapillary Carcinoma Component

Micropapillary carcinoma成分を伴ったS状結腸癌の1例

症例は78歳，女性．下腹部痛および排便時下血を主訴に当院を受診．大腸内視鏡検査にてS状結腸癌と診断され，S状結腸切除術を施行した．病理組織診断では明瞭な微小乳頭状形態を呈するmicropapillary carcinoma成分が腫瘍全体の約8割を占め，残りの約2割が中分化型腺癌であり，軽度のリンパ管侵襲を認めた．他臓器由来の癌と同様に大腸のmicropapillary carcinomaは予後不良であると報告されている．その頻度は少なく，文献的考察を含めて報告する．

A case of advanced gastric cancer with an invasive micropapillary carcinoma component

A case of advanced gastric cancer with an invasive micropapillary carcinoma component

Colorectal micropapillary carcinomas are associated with poor prognosis and enriched in markers of stem cells

Colorectal micropapillary carcinoma has recently been reported as an aggressive variant of adenocarcinoma with a high incidence of lymph node metastasis, but has not been well investigated in terms of survival analysis. This study analyzed the clinicopathological characteristics, including survival data, of the patients with micropapillary carcinoma. We hypothesized that the aggressive features of micropapillary carcinoma might be related to the presence of more tumor cells with stem cell phenotype in colorectal cancer. Fifty-five (10%) micropapillary carcinoma cases were identified among 561 cases of colorectal cancer. We compared the clinicopathological characteristics, including survival data and immunohistochemical profiles of stem cell markers (SOX2, NOTCH3, CD44v6, CD166, ALDH1) of micropapillary carcinomas with those of randomly selected 112 conventional adenocarcinomas lacking micropapillary carcinoma components (non-micropapillary carcinoma) in the colorectum. To exclude the possibility of dilution of control group by patients with microsatellite instability-high carcinomas, we divided non-micropapillary carcinomas into microsatellite instability-high carcinoma and microsatellite stable tumors. Micropapillary carcinomas were characterized by more frequent lymphovascular invasion (P<0.0001) and lymph node metastasis (P<0.0001), higher pathological T and tumor node metastasis stages (P=0.047 and P=0.001), and more frequent SOX2 (P=0.038) and NOTCH3 expressions (P=0.005). Overall 5-year survival rate for patients with micropapillary carcinoma (37%) was significantly lower than for microsatellite instability-high carcinoma and microsatellite stable carcinoma patients (92 and 72%, P<0.0001). The presence of the micropapillary carcinoma component was shown to be associated with a significantly worse survival rate in univariate (P<0.0001) and multivariate (P=0.003, Cox hazard ratio 2.402) analyses. In conclusion, recognition of the micropapillary carcinoma component in colonic adenocarcinoma is very important, because the micropapillary carcinoma has been associated with a significantly worse prognosis. We also found a higher expression rate of cancer stem cell markers in micropapillary carcinomas, suggesting their potential contribution to the survival disadvantage of micropapillary carcinoma.

Relationship between colorectal adenocarcinoma with invasive micropapillary carcinoma component and lymph node metastasis

To investigate the relationship between colorectal adenocarcinoma with invasive micropapillary carcinoma (IMPC) component, lymphovascular invasion, and lymph node metastasis. One hundred and thirty one cases of colorectal adenocarcinoma with invasive micropapillary carcinoma component were evaluated by H&E and immunohistochemical staining. The main pathological features, percentage of IMPC component, lymphovascular invasion, and lymph node metastasis were assessed and compared to 296 cases of conventional colorectal adenocarcinoma. The maximum diameter of the tumors of the IMPC group was significantly lower than the conventional group. The degree of differentiation, the lymph node metastatic rate, the average number of metastatic lymph nodes, the number of cases with lymphovascular tumor emboli were significantly higher in the IMPC group (P = 0.000). The rate of distant metastasis at operation was higher in the IMPC group (14.5%) compared to the conventional group (10.8%) even though statistical significance was not achieved (P = 0.278) . In IMPC group, as the IMPC component increased, the rate of lymph node metastasis also showed an increasing trend. The rate of lymph node metastasis were 53.0% (157/296) , 67.7% (42/62) and 85.5% (59/69) " respectively" for conventional adenocarcinoma, adenocarcinoma with ≤ 10% IMPC component and adenocarcinoma with > 10% IMPC component; the difference was statistically significant (P = 0.000). Compared to conventional colorectal adenocarcinomas, the colorectal carcinomas with IMPC component show a significantly higher rate of lymphovascular invasion, lymph node metastasis and distant metastasis. The percentage of IMPC component in colorectal adenocarcinoma is significantly correlated to the rate of lymph node metastasis. Therefore, presence of IMPC component and degree of tumor differentiation are predicting factors of lymph node metastasis.

Micropapillary carcinoma of the urinary bladder: a case report and review of the literature

Micropapillary carcinoma is an uncommon variant of urothelial carcinoma with high metastatic potential. The presence of micropapillary carcinoma component in bladder biopsies should alert urologists to its aggressive behaviour. We report the case of a 70-year-old man who presented with macroscopic hematuria lasting 2 weeks. Magnetic resonance imaging revealed a bladder tumour in the dome area extended to perivascular adipose. The transurethral biopsy showed a high-grade micropapillary carcinoma with muscle invasion. Radical cystectomy with lymph node dissection was then performed. The pathological examination revealed a high-grade purely micropapillary carcinoma invading the perivesical adipose. No tumour recurrence or metastasis were reported at the 6-month follow-up.

Colonic micropapillary carcinoma, a recently recognized subtype associated with histological adverse factors: clinicopathological analysis of 15 cases

Micropapillary carcinoma (MPC) is regarded as an aggressive variant of adenocarcinoma in any location. The reported proportion of a micropapillary carcinoma component in an entire tumour ranges from 5 to 95% and only one case of pure MPC has been reported. To date, approximately 130 cases of MPC in the colorectum have been reported, but it is likely that this small number is to some extent due to under-reporting because this pattern is not well recognized by the general pathologist. All previous studies have combined colonic and rectal primary tumours and most have only analysed patients with clinical Stages I or II. We analysed 15 cases of MPC of the colon alone, diagnosed in our institution, and compared them with 105 conventional carcinomas of the colon. An MPC component was present in 10% of all colonic carcinomas. These tumours presented at a median age of 56 years, and all were of American Joint Committee on Cancer Stages III and IV. Subserosal tissue invasion was present in every case, 60% had more than four positive lymph nodes, 60% were accompanied by poorly differentiated conventional carcinoma, 40% had had an incomplete resection and a third demonstrated lymphovascular invasion. Despite these adverse prognostic factors, tumours containing MPC showed the same survival, stage by stage, as conventional adenocarcinoma in multivariate analysis, although 3-year survival (81.7%vs 87.3%, P=0.035) was worse on univariate analysis. The histopathologist should be aware of the possibility of MPC. Three-year survival is worse than in patients with conventional colonic carcinomas in Stage III.

Clinicopathological significance of invasive micropapillary carcinoma component in invasive breast carcinoma

Invasive micropapillary carcinoma (IMP) of the breast is a rare variant of invasive breast carcinoma and most cases of IMP are associated with nodal metastasis and lymphatic invasion. Lesions composed of an IMP component alone are rare and almost always coexist with other pathological components. However, few reports have documented IMP along with its proportion and the coexistent pathological type. We analyzed the total 486 breast cancer lesions operated in our hospital in 1998. We classified the lesions into five groups by the proportion of the IMP component in each lesion. Then we evaluated the incidence of nodal metastasis and lymphatic invasion in each group. The incidence of the invasive carcinoma containing any IMP components was 8.4%. The incidence of nodal metastasis and lymphatic invasion in lesions with an IMP component were significantly higher than that in those with no IMP. No correlation was seen between the incidence of nodal metastasis and the coexistent pathological type, shape of tumor clusters, nuclear grade and the expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 and gross cystic disease fluid protein-15 in IMP components. The presence of IMP components was a significant predictive factor for nodal metastasis, even if it is detected in only a small proportion of the tumor.

Clinicopathological and molecular characterization of colorectal micropapillary carcinoma

Invasive micropapillary carcinoma is associated with frequent lymph node metastasis and adverse clinical outcome. Initially described as a variant of breast and ovarian carcinoma, it has subsequently been found in other organs, most recently the colon. Reports of colorectal micropapillary carcinoma to date are limited in number, and their molecular profile has not been established. The aims of the present study were to analyze their clinicopathological features and molecular profile, and compare them with those of conventional adenocarcinoma. Clinicopathological features of a cohort of 379 patients with primary colorectal cancer were retrospectively reviewed for the presence of the pattern characteristic of micropapillary carcinoma. We also assessed the expression of KRT7, KRT20, CEACAM5, MUC1 (EMA, clone E29), MUC1 (clone MA695), MLH1, MSH2, MSH6 and TP53 by immunohistochemistry. Genetic assessments of microsatellite instability, chromosomes 17p and 18q, and mutations in TP53, BRAF and KRAS were performed using DNA extracted from formalin-fixed, paraffin-embedded sections. In all, 60 of the reviewed cases (16%) had a micropapillary component that ranged from 5 to 95% of the tumor, characterized by a higher frequency of an infiltrative pattern, lymphovascular and perineural invasion, a higher depth of invasion and more positive lymph nodes than conventional adenocarcinoma. Immunohistochemistry for MUC1 (clone MA695) and MUC1 (EMA, clone E29) enhanced the characteristic inside–out staining pattern of the micropapillary carcinoma component, whereas the rest of the tumor showed luminal staining patterns. KRT7 expression was slightly increased in micropapillary carcinoma, but did not reach significance (17–3%, P=0.1967). The molecular parameters showed a higher frequency of TP53 alterations and a low incidence of microsatellite instability and RER phenotype (loss of mismatch repair protein) in micropapillary carcinoma. With regard to the histological parameters, micropapillary carcinoma appears to be more aggressive than conventional colorectal adenocarcinoma. The molecular profile supports the hypothesis that micropapillary carcinoma carcinogenesis develops through the classical chromosomal instability pathway.