Micropapillary Component Research Articles

Frequent aerogenous spread with decreased E-cadherin expression of ROS1-rearranged lung cancer predicts poor disease-free survival.

ROS1 rearrangement has been found in a subset of lung cancer and ROS1-rearranged tumors are sensitive to ALK kinase inhibitors. This study sought to evaluate the clinicopathological implications and histomorphological characteristics of ROS1-rearranged tumors, especially micropapillary and aerogenous spread growth and to investigate the usefulness of ROS1 immunohistochemistry as a diagnostic test for ROS1 rearrangement. ROS1 rearrangement characterizations by fluorescence in situ hybridization and ROS1 protein and E-cadherin expression by immunohistochemistry were performed using 754 non-small cell lung cancer surgical specimens. ROS1 rearrangement was identified in 10 samples. Histologically, all 10 ROS1-rearranged tumors harbored an adenocarcinoma component. Significantly, we noted a high association between ROS1 rearrangement with a micropapillary component (p<0.001), aerogenous spread (p=0.002), and E-cadherin loss (p=0.049). Survival analysis showed that ROS1 rearrangement was significantly associated with a higher risk of tumor recurrence (p=0.024). The best criterion to detect ROS1-rearrangement by immunohistochemistry was an H-score of ≥100, with a sensitivity and specificity of 90% and 93.5%, respectively. ROS1-rearranged adenocarcinoma exhibited distinct morphological and clinicopathological features. Decreased membranous E-cadherin expression and aerogenous spread may be associated with worse disease-free survival. ROS1 immunohistochemistry correlated well with ROS1 gene rearrangement.

Overexpression of Vascular Endothelial Growth Factor A in Invasive Micropapillary Colorectal Carcinoma.

Invasive micropapillary carcinoma (IMPC) is a rare variant of colorectal cancer with an adverse prognosis. "Retraction artifact" around tumor cells is a feature of IMPC. The aim of this study was to assess the nature of the retractions around the tumor cells and to describe the histopathological features of a group of 18 cases of IMPC. A pathology review of 128 consecutive colorectal cancers identified 18 cases of histologically proven IMPC using 5% of the total tumor volume comprised of a micropapillary component as the diagnostic criterion. Immunostains for D2-40, CD31, CD34, vascular endothelial growth factor A (VEGF-A), and mucin 1 (MUC-1) were performed using the avidin-biotin complex method. Cases of IMPC were characterized by pseudomicropapillae surrounded by lacunar-like clear spaces. These structures exhibited the inside-out growth pattern as highlighted by MUC-1 staining. The lining of the lacunar spaces was immunoreactive to CD31 but not CD34 or D2-40, indicating that they are neovascular structures. Furthermore, the tumor cells strongly and diffusely expressed VEGF-A. The strong coexpression of VEGF-A and CD31 suggests a prominent role of neoangiogenesis in these tumors.

Morphological and molecular characteristics of HER2 amplified urothelial bladder cancer.

Several (pre-) clinical trials are currently investigating the benefit of HER2-targeted therapy in urothelial bladder cancer (UBC). Patients with HER2 amplified UBC could potentially profit from these therapies. However, little is known about histomorphology, HER2 protein expression patterns and occurrence of alterations in the HER2 gene in their tumors. Among 150 metastasizing primary UBC, 13 HER2 amplified tumors were identified. Their histopathological features were compared with 13 matched, non-amplified UBC. HER2 protein expression was determined by immunohistochemistry. The 26 tumors were screened for mutations in exons 19 and 20 of the HER2 gene. UBC with HER2 amplification presented with a broad variety of histological variants (median 2 vs. 1), frequently featured micropapillary tumor components (77 % vs. 8 %) and demonstrated a high amount of tumor associated inflammation. Immunohistochemically, 10 of 13 (77 %) HER2 amplified tumors were strongly HER2 protein positive. Three tumors (23 %) were scored as HER2 negative. One of the HER2 amplified tumors harbored a D769N mutation in exon 19 of the HER2 gene; all other tested tumors were wild type. In conclusion, HER2 amplified UBC feature specific morphological characteristics. They frequently express the HER2 protein diffusely and are, therefore, promising candidates for HER2 targeted therapies. The detection of mutations at the HER2 locus might add new aspects to molecular testing of UBC.

Prevalent and up-regulated vimentin expression in micropapillary components of lung adenocarcinomas and its adverse prognostic significance.

The factors conferring the increased malignancy on lung adenocarcinoma with micropapillary component (AC-MPC) remain to be elucidated. On proteomics based on 2-dimensional gel electrophoresis, 19 proteins differentially expressed by more than 1.5-fold between AC-MPC and conventional adenocarcinoma (CAC); in particular, vimentin, one of the proteins, was 3.5-fold up-regulated in AC-MPC. Subsequent semi-quantitative investigation by immunohistochemistry with large cohorts comprised 101 AC-MPC and 119 CAC, respectively, of different stages revealed that vimentin was expressed in MPC of 95 (94.1%) AC-MPC and the expression scores were higher than those of well- and moderately differentiated CAC, as well as the background non-MPC of the AC-MPC (P < 0.0001), but not significantly different from those of poorly differentiated CAC (P = 0.561). Even within the AC-MPC entity, higher vimentin expression was correlated with more frequent vascular invasion and more advanced node metastasis (P < 0.02), and multivariate analysis showed that high vimentin expression and worse node statuses were independent indicators of adverse prognosis (P < 0.048). In conclusion, vimentin expression is prevalent and markedly up-regulated in MPC, which might reflect the biological essence of poorer differentiation or dedifferentiation of MPC, and this might have a role in the acquisition and increase of invasiveness and consequent more malignant nature of MPC.

Differences in Prognostic Factors and Failure Patterns Between Invasive Micropapillary Carcinoma and Carcinoma With Micropapillary Component Versus Invasive Ductal Carcinoma of the Breast: Retrospective Multicenter Case–Control Study (KROG 13-06)

PurposeWe designed the present study to investigate differences in prognostic factors and failure patterns between patients with invasive micropapillary carcinoma or carcinoma with micropapillary component (IMPC) and randomly matched patients with invasive ductal carcinoma (IDC) of the breast at multiple institutions of the Korean Radiation Oncology Group (KROG). Materials and MethodsThis retrospective multicenter study was performed using subjects treated from January 1999 to November 2011. Female patients who had undergone curative resection for breast cancer without neoadjuvant chemotherapy were considered for this study. Exact matches were made for age (± 3 years), pathologic tumor and node stage, treatment method (surgery with or without radiotherapy), and period when surgery was performed (within 1 year) at the same institution. ResultsA total of 534 patients were analyzed. The median follow-up period was 59 months in both groups. In the comparison of clinicopathologic characteristics, rates of lymphovascular invasion (LVI) and nuclear grade III were both significantly higher in IMPC than in IDC (P < .001, P = .01, respectively). During the follow-up period, recurrences developed in 40 patients with IMPC (15.0%) and 21 with IDC (7.9%). Locoregional recurrence (LRR) developed in 22 patients with IMPC (8.2%) and 10 with IDC (3.7%). The rate of distant metastasis did not differ between the 2 groups (P = .52). LRR-free survival (P = .03) and recurrence-free survival (P = .007) were significantly different between the 2 groups, but overall survival was not (P = .67). ConclusionIMPC is associated with a higher rate of LVI, high nuclear grade, and a propensity for LRR compared to IDC. Modification of the locoregional treatment modality might be needed in this pathologic subtype of breast cancer.

Solid Component and Tumor Size Correlate With Prognosis of Stage IB Lung Adenocarcinoma

Prognostic factors for stage IB lung cancer remain controversial. The International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society proposed a new classification for pulmonary adenocarcinoma. We investigated the prognostic value of this new classification in resected stage IB pulmonary adenocarcinoma. The study included 187 patients with stage IB pulmonary adenocarcinoma. All pathologic slides were reevaluated according to the new classification for pulmonary adenocarcinoma, with each histologic component recorded in 5% increments. Survival analyses were performed to determine the prognostic factors for stage IB pulmonary adenocarcinoma. Univariable analysis showed tumor size was prognostic for overall survival (hazard ratio [HR], 2.083; p<0.001) and progression-free survival (HR, 1.991; p < 0.001); gender (HR, 0.558; p= 0.033), presence of the solid component (HR, 1.976; p= 0.016), and presence of a micropapillary component (HR, 2.371; p= 0.018) were prognostic for progression-free survival. Multivariable analysis revealed that tumor size was an independent prognostic factor for overall survival (HR, 2.083; 95% confidence interval, 1.433 to3.029; p < 0.001) and progression-free survival (HR, 2.036; 95% confidence interval, 1.546 to 2.681; p < 0.001) and that thepresence of the solid component (HR, 2.045; 95% confidence interval, 1.172 to 3.568; p= 0.012) was an independentprognostic factor for progression-free survival. Solid component and tumor size significantly correlate with prognosis in stage IB pulmonary adenocarcinoma.

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

To identify those with a micropapillary pattern, ascertain relative frequency and document clinicopathological characteristics by reviewing gastric carcinomas. 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 least 5% of the tumor. Tumor tissues from these 5 invasive gastric carcinomas were immunostained using an anti-mucin 1 (MUC1) antibody (clone MA695) to detect the characteristic inside-out pattern and with D2-40 antibody 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 dUTP-biotin nick end-labeling (TUNEL) method and immunohistochemistry for activated caspase-3 (clone C92-605). 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 (≥ pT2) 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 apoptotic neutrophils 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. This is the first study showing phagocytosis (cannibalism) of apoptotic neutrophils by tumor cells in gastric micropapillary carcinomas.

Cytoplasmic maspin expression is a predictor of poor prognosis in patients with lung adenocarcinoma measuring

Maspin is known to be a tumour suppressor protein, and few studies focused upon its prognostic significance in patients with small-size lung adenocarcinoma have been reported; however, its clinical significance remains controversial. We explored the prognostic value of maspin with particular reference to its subcellular localization in patients with resected lung adenocarcinoma measuring <3cm. Immunohistochemical analyses were performed on resected 110 specimens of lung adenocarcinoma measuring <3cm. Maspin positivity was defined as strong expression in only the cytoplasm and was observed in 27 patients (24.5%). It correlated significantly with the presence of lymph node metastasis (P=0.009) and micropapillary component (P<0.001). The patients were followed-up for 6-88months (median: 71months), and the maspin-positive group had shorter disease-free survival (DFS) and overall survival (OS) by log-rank test (P<0.001, P<0.001, respectively). Using Cox's multivariate analysis, the status of maspin was an independent prognostic factor for DFS and OS (P=0.004, P=0.022, respectively), as well as lymph node metastasis. Cytoplasmic maspin expression could be an independent poor prognostic indicator of patients with lung adenocarcinoma measuring <3cm.

Correlation of histological components with tumor invasion in pulmonary adenocarcinoma.

BackgroundPulmonary adenocarcinoma (PA) is the most common histologic type of primary lung cancer. Generally, adenocarcinoma was composed by five major components. The present study aimed to evaluate changes in the composition of adenocarcinoma components as the tumor grows; in addition, to analyze the correlation between the occupancy rates of histologic components of the tumor in regard to prognosis.MethodsPathologic data were retrospectively evaluated for 206 patients who underwent curative resection of PA. We investigated how histologic component occupancy rates changed as tumor size and N stage increased. To evaluate local invasiveness, the major components of the present group and absent group of pleural invasion, lymphatic invasion, and vascular invasion were compared.ResultsThe mean percentages of acinar and solid components significantly increased with an increase in size (P = 0.006, P < 0.001) ; however, the percentage of lepidic components decreased (P < 0.001). In cases with a solid component and a micropapillary component, a gradual increase was found with an increase N stage (P = 0.001, P < 0.001); however the percentage of lepidic components decreased (P < 0.001). Average differences of histologic components dependent upon whether pleural, lympathic and vascular invasion were present, the difference of micropapillary and lepidic components were statistically significant. With logistic regression analysis, as the occupancy rate of the lepidic component increased, the probability of pleural invasion, lymphatic invasion, and vascular invasion decreased; in cases with a micropapillary component, as the occupancy rate of increased, the probability of lymphatic invasion and vascular invasion increased. In multivariate analysis using the Cox propotional hazards model, the occupancy rates of acinar(p = 0.043; odds ratio = 1.023), micropapillary(p = 0.002; odds ratio = 1.051) and lepidic (p = 0.005; odds ratio = 0.966) components were significantly associated with recurrence.ConclusionsThe lower the occupancy rate of a lepidic component and the higher the occupancy rates of acinar, solid, and micropapillary components, the likelihood of tumor progression increased. In addition, as the occupancy rate of a lepidic component decreased and a micropapillary component increased, local invasiveness and recurrence rate increased; thus, increasing the probability of a poor prognosis.

A Rare Case of Mesothelioma Showing Micropapillary and Small Cell Differentiation with Aggressive Behavior

Pleural mesothelioma is a rare neoplasm and roughly 70% are the epithelioid type, which is characterized by proliferation of epithelioid tumor cells with a tubulopapillary growth pattern [1]. There have been few reports of mesothelioma having a micropapillary pattern [2] and a small cell component [3]. To the best of our knowledge, there has been no previously reported case containing both micropapillary and small cell components. Herein, we report a rare case of mesothelioma with micropapillary component and small cell differentiation exhibiting aggressive behavior in a 59-year-old woman.

A Comprehensive Investigation of Molecular Features and Prognosis of Lung Adenocarcinoma with Micropapillary Component

Both micropapillary predominant lung adenocarcinoma according to the IASLC/ATS/ERS classification and lung adenocarcinoma with a micropapillary component have been reported to be associated with poor prognosis. However, whether they have different prognosis remains undetermined. Out of 1302 lung adenocarcinoma patients, 21 patients with micropapillary predominant lung adenocarcinoma (MPP) and 100 patients with nonmicropapillary predominant tumors harboring a micropapillary component of at least 5% (MPC) were investigated for clinicopathologic characteristics, recurrence-free survival (RFS), overall survival (OS), and spectrum of well-identified driver mutations including EGFR, KRAS, HER2, BRAF, ALK, ROS1, and RET. Twenty out of 21 (95.2%) micropapillary predominant lung adenocarcinoma harbored driver mutations in EGFR (85.7%), HER2 (4.8%), or RET (4.8%). MPP had significantly worse RFS than MPC in stage I patients (p = 0.003), but not in stages II-III patients. The overall survival was comparable between MPP and MPC regardless of disease stages. Objective response was achieved in 13 out of the 18 MPP or MPC patients with EGFR mutations who received EGFR tyrosine kinase inhibitors (TKIs) after disease recurrence. The postrecurrence survival was significantly better in EGFR-mutated patients who were treated with EGFR TKIs compared to those who did not receive TKIs (p = 0.003). Micropapillary predominant lung adenocarcinoma is a disease that could be largely defined by targetable driver mutations. For stage I lung adenocarcinoma, MPP was even more likely to recur than MPC. EGFR TKIs might help to control the recurrent disease for MPP or MPC patients harboring EGFR mutations.

Micropapillary pattern and poorly differentiated clusters represent the same biological phenomenon in colorectal cancer: a proposal for a change in terminology.

Colorectal carcinomas (CRCs) with a micropapillary pattern and those showing high counts of poorly differentiated clusters (PDCs) are characterized by a higher probability to develop nodal metastases and have a worse prognosis. In light of the morphologic similarity to the micropapillary component, we aimed to verify whether PDCs also display an inverted secretory pattern. The immunohistochemical expression of MUC1 and E-cadherin was assessed in a cohort of CRCs with PDCs and compared with that observed in CRCs without PDCs. PDCs in our cases always displayed an inverted MUC1 pattern. In addition, we found abnormal (lost or cytoplasmic) expression of E-cadherin in PDCs. The altered expression of MUC1 and E-cadherin may account for the aggressive behavior and higher metastatic potential of CRCs with high PDC counts and indicate an epithelial-mesenchymal transition. Our findings suggest that regardless of the morphologic aspect, PDCs and the micropapillary component may reflect the same biological phenomenon in CRCs. Thus, we wonder whether the micropapillary areas should be considered a variant of CRCs or more objectively counted as PDCs to predict prognosis. We also believe that the term PDC better describes the biological phenomena underlying this peculiar morphologic aspect in comparison with the misnomer micropapillary.

High-grade lung adenocarcinomas with micropapillary and/or solid patterns: a review.

The purpose of review is to discuss the most recent research findings on lung adenocarcinomas with solid and micropapillary patterns. Multiple recent studies have confirmed that both patterns are associated with adverse clinicopathologic features such as lymphovascular and pleural invasion, as well as lymph node metastasis, and consequently with poor disease-free survival, overall survival, or both. Radiologic characteristics such as high F-fluorodeoxyglucose (FDG) uptake, a solid nodule, and size ≥2 cm have been found to be useful to detect solid and micropapillary patterns. A seminal study has shown that the presence of a micropapillary component (≥5%) is a risk factor for early locoregional recurrence in patients undergoing limited resection for small (<2 cm) adenocarcinomas, but not for patients undergoing lobectomy. Several studies have demonstrated that micropapillary-predominant tumors are associated with EGFR mutations, whereas solid-predominant tumors are negatively associated with mutations of this gene and positively associated with KRAS mutations, indicative of the lack of response to EGFR tyrosine kinase inhibitors. The possible role of molecular events such as loss of BRG1/BRM and activation of c-Met has been identified in solid pattern and micropapillary pattern, respectively. Micropapillary and solid patterns are markers for early recurrence and poor survival in lung adenocarcinomas. In order to overcome the unfavorable outcomes, the preoperative detection of these patterns, development of targeted therapy for KRAS mutants, and discovery of biomarkers that play a significant role in development or progression or both of these patterns are warranted to help in treating lung adenocarcinoma patients with micropapillary or solid patterns or both effectively.

Recent advances and clinical implications of the micropapillary histological subtype in lung adenocarcinomas.

Micropapillary (MIP) histologic subtype included in the classification of lung adenocarcinomas (ADCs) is associated with both size- and stage-independent poor prognoses. MIP pattern in lung ADCs, even at small, early stages, correlates with high lymphovascular invasion, visceral pleural invasion and lymph node metastases. Recently, we reported that patients with a MIP component are at a higher risk of locoregional recurrence after limited resection. Identification of a MIP pattern is only possible with permanent pathologic sections; preoperative imaging, cytology or intraoperative frozen section specimens remain unreliable. The intermixed, heterogenous morphology of lung ADC presents a technical challenge in investigating the molecular biology of cells with MIP morphology. A comprehensive understanding of the biology of MIP morphology is vital for therapeutic interventions.

Non-sarcomatous spindle cell morphology in conventional lung adenocarcinoma: a clinicopathological study.

Non-sarcomatous spindle cell foci (N-SSCF) without aggressive invasiveness, also called morule-like lesions, occur occasionally in conventional lung adenocarcinoma, but their characteristics remain poorly understood. We identified N-SSCF in 7 (4.0 %) of 173 lung adenocarcinomas and examined their clinicopathological features. The patients were six men and one woman with a mean age of 57.0 years (range, 43-76 years). All tumors were papillary-predominant adenocarcinomas, ranging in size from 1 to 4.5 cm (mean, 2.7 cm). N-SSCF occupied 10-30 % of the tumors, and in all cases, there were focal or multifocal transitions between the two morphotypes. Most N-SSCF were plug-like nodules filling the spaces of cancerous alveoli/tubules or patchy insular nests. N-SSCF frequently contained mucin + lumina and were positive for cytokeratin 7, thyroid transcription factor 1, and Napsin A, but negative for cytokeratin 5/6 and vimentin, similar to the adenocarcinoma cells of the same tumor. Five cases (71 %) were at stage I or II, suggesting that N-SSCF can occur in an early phase of lung cancer. In an age-, sex-, and stage-matched control study, N-SSCF were not associated with prognosis (P = 0.471). We consider tumors with N-SSCF a distinct structural variant of adenocarcinoma without prognostic significance. They should be distinguished from true sarcomatous spindle cells and micropapillary components, which are associated with aggressive behavior.

Prognostic Significance of Adenocarcinoma In Situ, Minimally Invasive Adenocarcinoma, and Nonmucinous Lepidic Predominant Invasive Adenocarcinoma of the Lung in Patients With Stage I Disease

According to the IASLC/ATS/ERS classification, the lepidic predominant pattern consists of 3 subtypes: adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and nonmucinous lepidic predominant invasive adenocarcinoma. We reviewed tumor slides from 1038 patients with stage I lung adenocarcinoma, recording the percentage of each histologic pattern and measuring the invasive tumor size. Tumors were classified according to the IASLC/ATS/ERS classification: 2 were AIS, 34 MIA, and 103 lepidic predominant invasive. Cumulative incidence of recurrence (CIR) was used to estimate the probability of recurrence. Patients with AIS and MIA experienced no recurrences. Patients with lepidic predominant invasive tumors had a lower risk for recurrence (5-y CIR, 8%) than nonlepidic predominant tumors (n=899; 19%; P=0.003). Patients with >50% lepidic pattern tumors experienced no recurrences (n=84), those with >10% to 50% lepidic pattern tumors had an intermediate risk for recurrence (n=344; 5-y CIR, 12%), and those with ≤10% lepidic pattern tumors had the highest risk (n=610; 22%; P<0.001). CIR was lower for patients with ≤2 cm tumors than for those with >2 to 3 cm tumors (for both total and invasive tumor size), with the difference more pronounced for invasive tumor size (5-y CIR, 13% vs. 21% [total size; P=0.022] and 12% vs. 27% [invasive size; P<0.001]). Most patients with lepidic predominant adenocarcinoma who experienced a recurrence had potential risk factors, including sublobar resection with close margins (≤0.5 cm; n=2), 20% to 30% micropapillary component (n=2), and lymphatic or vascular invasion (n=2). It therefore may be possible to identify lepidic predominant adenocarcinomas that carry a low or high risk for recurrence.

Primary lung adenocarcinoma with morule-like components: A unique histologic hallmark of aggressive behavior and EGFR mutation

BackgroundLung adenocarcinoma with morule-like components is an unusual variant of lung adenocarcinoma, comprising uniform, tightly packed spindle-shaped cells, which fill the lumen of the glandular structures of the carcinoma. The aim of the study was to outline the clinicopathologic features of this variant. Patients and methodsWe examined a series of 904 surgically resected adenocarcinomas. We defined morule-like components as small buds of spindle-cell proliferation in the tumor lumen of the glandular structures of the carcinoma and calculated their proportion of total tumor mass. Targeted genotyping was performed for KRAS, EGFR, HER2, and BRAF. ALK rearrangements were analyzed immunohistochemically. Immunopositive cases were confirmed using RT-PCR and/or FISH. ResultsWe detected 17 cases of adenocarcinoma with morule-like components. This variant, representing only 1.9% was associated with unfavorable outcomes and a mutation in the EGFR. Histologic examination revealed adenocarcinoma with morule-like components accounting for 5−50% of tumors. Among the morule-like components, 10 (58.8%) of the 17 samples showed intracytoplasmic lumina formation containing eosinophilic mucinous material. The presence of micropapillary components in adenocarcinoma with morule-like components suggests that morule-like components could be merely excessive growth of the micropapillary pattern. However, our results indicated no statistical differences in the MIB-1 indices of the morule-like components and the adjacent tumor components or the micropapillary components. The univariate and multivariate analyses revealed a correlation between the presence of a morule-like components and an unfavorable outcome. ConclusionsOur study clearly indicated that adenocarcinoma with morule-like components is distinct unfavorable prognostic and predictor for EGFR mutation.

Clinical Outcome of Patients with T1 Micropapillary Urothelial Carcinoma of the Bladder

We report cancer specific outcomes of micropapillary nonmuscle invasive bladder cancer. We retrospectively reviewed the records of 36 cases restaged within 3 months of the initial diagnosis of micropapillary nonmuscle invasive bladder cancer. Early radical cystectomy within a 3-month landmark after restaging transurethral bladder tumor resection or conservative treatment with intravesical bacillus Calmette-Guérin, surveillance or deferred radical cystectomy was offered according to surgeon and patient preference. The cumulative incidence of cancer specific mortality and metastasis was estimated using the Kaplan-Meier method. Differences in the cumulative incidence of cancer specific mortality and metastasis between the groups were tested using the log rank test. Median patient age was 68 years (IQR 63-77). The male-to-female ratio was 3:1. At restaging all patients had cT1 disease or less. Early radical cystectomy was performed in 15 patients (42%) while 21 (58%) underwent conservative treatment. Median followup after landmark in cancer specific survivors was 3.1 years (IQR 1.1-5.9). The 5-year cumulative incidence of cancer specific mortality was 17% in the early radical cystectomy group and 25% in the conservative management group for an absolute difference of 7% (95% CI -26-41, p= 0.8). The 5-year cumulative incidence of metastasis was 21% and 34%, respectively, with an absolute difference of 13% (95% CI -23-49, p = 0.9). The extent of the micropapillary component was not significantly associated with cancer specific mortality (p = 0.4) or metastasis (p = 0.9). Using proper selection criteria, including patient and pathological factors, certain patients in whom cT1 micropapillary urothelial carcinoma was managed conservatively did not have significantly worse outcomes than patients treated with early radical cystectomy.

Micropapillary component in gastric adenocarcinoma: an aggressive variant associated with poor prognosis

Adenocarcinomas with a micropapillary component (MPC) have been described as an unusual morphological variant in various organs. However, few reports have described MPCs in gastric carcinomas, and the clinicopathological features of MPC are unclear. Immunohistochemistry was used to detect the expression of epithelial membrane antigen, CK7, CK20, p53, epidermal growth factor receptor, β-catenin, c-erbB-2, and Ki-67. Correlation of the MPC to tumor stage, lymph node metastasis, and lymphovascular invasion was performed using Fisher's exact test. Kaplan-Meier estimates were used to analyze overall survival. Immunohistochemical staining demonstrated that micropapillary and conventional gastric carcinomas showed similar positivity rates for all markers. However, aberrant expression of E-cadherin was detected in the tumors with MPCs without immunoreactivity in the stroma face. Epithelial membrane antigen showed the characteristic inside-out staining pattern of MPCs. Lymphatic invasion (P = 0.003), venous invasion (P = 0.017), lymph node metastasis (P = 0.014), and tumor stage (P = 0.022) were significantly increased in patients with MPCs when compared with conventional adenocarcinomas. MPC subtype II had a significantly higher frequency of lymph node metastasis than subtype I (P = 0.014). However, the proportion of MPC was not associated with lymph node metastases (P = 0.136). Overall survival of patients with an MPC was significantly shorter than that of patients with conventional adenocarcinomas (P = 0.031). In addition, overall survival was significantly lower in patients with a subtype II MPC growth pattern than in those with subtype I MPC in gastric carcinomas (P = 0.040). Gastric adenocarcinomas with MPC appear to be an aggressive variant associated with a poor prognosis. MPCs occurring in gastric adenocarcinomas should be included in surgical pathology reports, even if the proportion of MPC in the lesions is very low in the lesion.

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.