Presence Of Micropapillary Pattern Research Articles

Micropapillary Pattern in Invasive Mucinous Adenocarcinoma of the Lung: Comparison With Invasive Non-Mucinous Adenocarcinoma.

Background. The presence of a micropapillary pattern is associated with poor outcomes in lung adenocarcinoma. This study aimed to assess the clinicopathological features of micropapillary pattern in mucinous adenocarcinoma of the lung. Methods. The patients were stratified into three groups: the invasive mucinous adenocarcinoma group (60 patients), the mixed invasive mucinous adenocarcinoma group (33 patients), and the invasive non-mucinous adenocarcinoma group (237 patients). The presence of micropapillary pattern and its clinicopathological features were analyzed and compared between the three groups. Results. Compared to mixed invasive mucinous adenocarcinoma, invasive mucinous adenocarcinoma had lower frequencies of micropapillary pattern (28.3% vs 87.9%, respectively; P < .001) and lymph node metastasis (00.0% vs 15.1%, respectively; P = .005). The frequency of tumor spread through air space (STAS) in invasive mucinous adenocarcinoma (23.3%) was higher than that in invasive non-mucinous adenocarcinoma (6.3%; P < .001), while lower than that in mixed invasive mucinous adenocarcinoma (60.6%; P < .001). When the three groups were all accompanied by micropapillary pattern, there was no obvious difference in STAS between invasive mucinous adenocarcinoma with micropapillary pattern and mixed mucinous adenocarcinoma with micropapillary pattern (P > .05). No filigree pattern occurred in invasive mucinous adenocarcinoma with micropapillary pattern. Conclusions. The micropapillary pattern is frequently observed in invasive mucinous adenocarcinoma and has a better prognosis compared to mixed invasive mucinous adenocarcinoma and invasive non-mucinous adenocarcinoma. However, the malignancy of the micropapillary pattern in mixed mucinous adenocarcinoma was similar to that in invasive non-mucinous adenocarcinoma, even with the presence of mucus. These findings suggest that the development mechanisms of the micropapillary pattern in invasive mucinous adenocarcinoma and mixed mucinous adenocarcinoma may differ.

Ovarian serous borderline tumors with recurrent or extraovarian lesions: a Japanese, retrospective, multi-institutional, population-based study.

Ovarian serous borderline tumors (SBT) are typically unilateral and are primarily treated using hysterectomy and bilateral salpingooophorectomy (SO). However, most young patients prefer fertility-sparing surgeries (FSS) with tumorectomy or unilateral SO. Micropapillary morphology and invasive implants have been designated as histopathological risk indicators for recurrence or metastasis, but their clinical impact remains controversial because of limitations like diagnostic inconsistency and incomplete surgical staging. A nationwide multi-institutional population-based retrospective surveillance was conducted with a thorough central pathology review to reveal the clinical features of SBT. Of 313 SBT patients enrolled in the Japanese Society of Clinical Oncology's Surveillance of Gynecologic Rare Tumors, 289 patient records were reviewed for clinical outcomes. The glass slides of patients at stage II-IV or with recurrence or death were re-evaluated by three gynecological pathologists. The 10-year overall and progression-free survival (PFS) rates were 98.6% and 92.3%. The median recurrence period was 40months and 77.0% was observed in the contralateral ovary within 60months. Patients aged ≤ 35years underwent FSS more frequently and relapsed more (p < .001). A clinic-pathological analysis revealed diagnosis during pregnancy, FSS, and treatment at non-university institutes as well as advanced stage and large diameter were independent risk factors of recurrence. Among patients having pathologically confirmed SBTs, PFS was not influenced by the presence of micropapillary pattern or invasive implants. The recurrence rate was lower in this cohort than previous reports, but the clinical impacts of incomplete resection and misclassification of the tumor were still significant on the treatment of SBT.

Evolutionary characterization of lung adenocarcinoma morphology in TRACERx.

Lung adenocarcinomas (LUADs) display a broad histological spectrum from low-grade lepidic tumors through to mid-grade acinar and papillary and high-grade solid, cribriform and micropapillary tumors. How morphology reflects tumor evolution and disease progression is poorly understood. Whole-exome sequencing data generated from 805 primary tumor regions and 121 paired metastatic samples across 248 LUADs from the TRACERx 421 cohort, together with RNA-sequencing data from 463 primary tumor regions, were integrated with detailed whole-tumor and regional histopathological analysis. Tumors with predominantly high-grade patterns showed increased chromosomal complexity, with higher burden of loss of heterozygosity and subclonal somatic copy number alterations. Individual regions in predominantly high-grade pattern tumors exhibited higher proliferation and lower clonal diversity, potentially reflecting large recent subclonal expansions. Co-occurrence of truncal loss of chromosomes 3p and 3q was enriched in predominantly low-/mid-grade tumors, while purely undifferentiated solid-pattern tumors had a higher frequency of truncal arm or focal 3q gains and SMARCA4 gene alterations compared with mixed-pattern tumors with a solid component, suggesting distinct evolutionary trajectories. Clonal evolution analysis revealed that tumors tend to evolve toward higher-grade patterns. The presence of micropapillary pattern and 'tumor spread through air spaces' were associated with intrathoracic recurrence, in contrast to the presence of solid/cribriform patterns, necrosis and preoperative circulating tumor DNA detection, which were associated with extra-thoracic recurrence. These data provide insights into the relationship between LUAD morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk.

Vessel invasion as a predictive factor for recurrence after surgery in stage I lung adenocarcinoma.

Patients with early-stage lung cancer who underwent R0 resection often encounter disease recurrence, especially during the early phase; thus, it is deemed vital to determine the predictive factors for recurrence after surgery. In this study, we aimed to identify the independent variables associated with recurrence after complete surgical resection of pathological stage I lung adenocarcinoma. We retrospectively reviewed the medical records of 169 patients who underwent pulmonary resection for primary lung adenocarcinoma pathological stage I with curative intent lung cancer surgery from 2015 to December 2018at our institution for information on the recurrence of the disease. Per the multivariate analysis, the presence of micropapillary pattern and vessel invasion were found to be independent predictors of disease recurrence after surgery (odds ratio [OR]: 9.36, 95% confidence interval [CI]: 2.42-36.2, P=0.0012; and OR: 4.50, 95% CI: 1.52-13.4, P=0.0068, respectively). Vessel invasion was also found to be an independent predictor of disease recurrence after surgery within a year (OR 11.4, 95% CI 3.08-42.5, P=0.0003). The presence of vessel invasion may help in distinguishing patients with the highest risk of early-phase disease recurrence after surgery. Patients with stage I adenocarcinoma with vessel invasion should undergo intensive surveillance after surgery.

Prognostic significance of tumor spread through air spaces in patients with stage IA part-solid lung adenocarcinoma after sublobar resection

ObjectivesThe purpose of this study was to assess the clinicopathologic implications of tumor spread through air spaces (STAS) in patients with stage IA part-solid lung adenocarcinoma after sublobar resection. Materials and methodsMedical records of patients with stage IA part-solid adenocarcinoma who underwent curative pulmonary resection between February 2009 and December 2016 were retrospectively reviewed. The clinicopathological features of STAS and its influence on postoperative recurrence and survival were investigated. ResultsAmong the 115 patients with stage IA part-solid adenocarcinoma who underwent wedge resection, 20 (17.4 %) had STAS. The multivariable analysis showed presence of STAS [HR (hazard ratio), 9.447; p = 0.002) and a larger invasive component size (HR, 1.097; p = 0.034) were independent risk factors for recurrence. The 5-year freedom from recurrence rates were 62.4 % and 97.9 % in cases with and without STAS, respectively (p < 0.001), and the 5-year disease-free survival rates were 58.5 % and 97.9 % in cases with and without STAS, respectively (p < 0.001). The presence of STAS was associated with old age (p = 0.030), male gender (p = 0.023), acinar predominant histologic pattern (p = 0.004), presence of micropapillary pattern (p < 0.001), lymphovascular invasion (p < 0.001) and larger invasive component (p < 0.001). ConclusionSTAS could be an important prognostic factor in patients with stage IA part-solid lung adenocarcinoma after sublobar resection. Effective preoperative evaluation and postoperative surveillance may help improve the outcome of patients with small part-solid nodules, particularly when accompanied by STAS.

Villin is a biomarker for reverse polarity in colorectal micropapillary carcinoma.

Colorectal cancer (CRC) is a common malignant tumor of digestive system. CRC with micropapillary pattern (MPP) is an aggressive variant of colorectal adenocarcinoma. The aim of the present study was to clarify the clinicopathological significance and the prognostic role of an immunohistochemical marker, MPP, in CRC. The association between MPP and clinicopathological characteristics and prognosis in 286 cases of CRC (286/453 cases had follow-up information) were analysed. Then, 81 tissues without MPP and 90 tissues with MPP were analysed by immunohistochemistry using antibodies against villin, E-cadherin and epithelial membrane antigen (EMA). Bioinformatics was used to evaluate the expression of these three indicators in CRC. The proportion of micropapillary carcinoma in the overall tumour was ≥5%, and was observed in 90/453 cases (19.8%). The present data showed that CRC with MPP displayed higher rates of vascular and lymphatic invasion, a higher metastatic lymph node ratio and a higher pathological tumour and metastasis stage compared with CRC without MPP. The positive expression rates of EMA, E-cadherin and villin were 50.3, 93.4 and 96.5%, respectively. In 90 CRC cases with MPP, EMA inside-out pattern (I/OP) staining was observed in 26 cases (28.9%), and it was often focal and partial, while 37 cases (41.1%) had E-cadherin focal and partial staining compatible with reverse polarity. Villin I/OP staining was observed in 77 cases (85.6%), and circumferential staining predominated over partial staining. Overall, the data suggested that the presence of MPP is significantly associated with aggressive tumour behaviour and worse overall survival rate in CRC. Visualization and distinction of reverse polarity of colorectal micropapillary carcinomas is improved villin compared with EMA or E-cadherin.

Frequent appearance of club cell (Clara cell)-like cells as a histological marker for ALK-positive lung adenocarcinoma.

Anaplastic lymphoma kinase-rearranged (ALK+ ) lung cancers show characteristic histological features, such as solid signet ring cell patterns and mucinous cribriform patterns; however, these features are not always observed in ALK+ lung cancers. We noticed that club cell (Clara cell)-like cells (CLCs) were frequently present in the papillary portion of ALK+ lung adenocarcinomas. In this study, we investigated the importance of CLCs in papillary patterns of ALK+ lung cancers. We compared the histological features of 18 ALK+ cases with 62 control cases (22 epidermal growth factor receptor-positive (EGFR+ ) and 40 ALK- and EGFR-negative (ALK- /EGFR- ) cases). The present study analyzed presence of papillary pattern, proportion of papillary pattern area, presence of micropapillary pattern, frequency of CLCs and lengths of snout. The frequency of CLCs in ALK+ cases was significantly higher than that in EGFR+ cases and ALK- /EGFR- cases. Micropapillary pattern was more frequently observed in ALK+ cases than that in ALK- /EGFR- cases (P < 0.001). The present study indicated that the high frequency of CLCs in papillary patterns was significantly associated with ALK+ cases. When solid signet ring cell patterns and mucinous cribriform patterns are absent, the high frequency of CLCs in papillary adenocarcinoma could be a useful histological marker for ALK+ lung cancers.

Diagnostic upgrade of atypical ductal hyperplasia of the breast based on evaluation of histopathological features and calcification on core needle biopsy.

Atypical ductal hyperplasia (ADH) of breast is increasingly diagnosed in core needle biopsy (CNB). As higher-grade lesions were found in the excision in a substantial proportion of ADH on CNB, factors predicting risk of subsequent upgrade are clinically significant. This study aims to investigate relevant histopathological factors in CNB that could predict diagnostic upgrade at excision. One hundred and forty-three cases of CNB with paired subsequent excision were evaluated for multiple clinicopathological parameters related to CNB sampling, ADH morphology, calcification and other co-existing histological features, and which of these parameters were associated with diagnostic upgrade at subsequent excisions were determined. Forty-eight cases (34.3%) were upgraded to malignancy, including 15 invasive cancers and 33 ductal carcinomas in situ (DCIS). An increased tissue area occupied by ADH (P=0.026), a higher number of ADH foci (P=0.004), the presence of solid pattern (P=0.037) and older age (P=0.012) were positively associated with upgrade, while negative associations were found with the presence of micropapillary pattern (P=0.025), co-existing columnar cell lesions (CCL) (P=0.001) and the presence of calcifications (P=0.009). Multivariate logistic regression analysis showed that the number of ADH foci (HR=2.810, P=0.013) was an independent positive predictor, while co-existing CCL (HR=0.391, P=0.013) was an independent negative predictor for upgrade. Patients with ADH in CNB showing the presence of co-existing CCL and a lower number of ADH foci have a lower risk of disease upgrade at excision, and are potential candidates for observation-only management.

Factors predicting occult lymph node metastasis in completely resected lung adenocarcinoma of 3 cm or smaller.

The aim of the study is to demonstrate the relationship between clinicopathological variables and occult lymph node metastasis in resected lung adenocarcinoma. The clinicopathological characteristics of 471 patients with clinical N2-negative status undergoing resection for lung adenocarcinoma of 3 cm or smaller at Taipei Veterans General Hospital between 2004 and 2012 were retrospectively reviewed. The association between clinicopathological variables and lymph node metastasis was analysed by univariate and multivariate logistic regression. Among the 471 patients, there were 386 (82.0%) patients with pathological N0 status, 35 (7.4%) with pathological N1 status and 50 (10.6%) with pathological N2 status. Greater tumour size (P = 0.002), presence of a micropapillary pattern (P < 0.001), presence of a solid pattern (P < 0.001) and predominant pattern group (micropapillary/solid predominant) (P = 0.001) were significantly associated with higher percentage of occult N2 lymph node metastasis. In multivariate analysis, greater tumour size (P = 0.008), presence of micropapillary pattern (P < 0.001) and presence of solid pattern (P = 0.001) were significant predictors of occult N2 lymph node metastasis in tumours of 3 cm or smaller. When histological pattern was entered as the predominant pattern in multivariate analysis, micropapillary/solid predominant pattern (P = 0.005) was also a significant predictor of occult N2 lymph node metastasis. The presence of micropapillary or solid pattern, as well as micropapillary/solid predominant pattern, is significantly associated with occult N2 lymph node metastasis in lung adenocarcinoma. Radical mediastinal lymph node dissection may help to identify occult lymph node metastasis in these patients.

International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification predicts occult lymph node metastasis in clinically mediastinal node-negative lung adenocarcinoma.

We investigated the role of the 2011 International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) classification in predicting occult lymph node metastasis in clinically mediastinal node-negative lung adenocarcinoma. We reviewed lung adenocarcinoma patients who had clinically N2-negative status, were evaluated by preoperative positron emission tomography combined with computed tomography (PET/CT) and had undergone lobectomy or pneumonectomy at Memorial Sloan Kettering Cancer Center (n = 297). Tumours were classified according to the 2011 IASLC/ATS/ERS classification. The associations between occult lymph node metastasis and clinicopathological variables were analysed using Fisher's exact test and logistic regression analysis. Thirty-two (11%) cN0-1 patients had occult mediastinal lymph node metastasis (pN2) whereas 25% of cN1 patients had pN2 disease. Increased micropapillary pattern was associated with increased risk of pN2 disease (P = 0.001). On univariate analysis, high maximum standard uptake value of the primary tumour on PET/CT (P = 0.019) and the presence of micropapillary (P = 0.014) and solid pattern (P = 0.014) were associated with occult pN2 disease. On multivariable analysis, micropapillary pattern was positively associated with risk of pN2 disease (odds ratio = 3.41; 95% confidence intervals = 1.42-8.19; P = 0.006). The presence of micropapillary pattern is an independent predictor of occult mediastinal lymph node metastasis. Our observations have potential therapeutic implications for management of early-stage lung adenocarcinoma.

Micropapillary Pattern at the Invasive Front and Its Association with Unresectable Colorectal Carcinomas

Unresectable colorectal carcinomas (CRCs) as considered incurable even if the primary tumors and the metastatic ones can undergo resection are correlated with poor prognosis. We evaluated the association between micropapillary pattern at the invasive front and unresectable CRCs. Thirty-four out of 264 (12.9%) CRC patients with stages III and IV were unresectable cases. The patients with unresectable CRCs had significantly worse survival than those with resectable CRCs (P < 0.001). Micropapillary pattern was evident in 12 (4.5%) out of 264 cases. This pattern was observed in 6 of 34 (17.6%) unresectable CRCs and in 6 of 230 (2.6%) resectable cases (P = 0.002). Unresectable CRCs revealed more frequently deeper invasion (odds ratio (OR), 1.175; 95% confidence interval (CI), 1.113–1.241), lymph node metastasis (OR, 2.356; 95% CI, 1.132–4.905), and presence of micropapillary pattern at the invasive front (OR, 8.000; 95% CI, 2.415–26.504) as compared to resectable cases. By multivariable logistic regression analysis, only micropapillary pattern was shown to be an independent predictor of unresectable CRCs (OR, 9.451; 95% CI, 2.468–36.196; P < 0.001). In conclusion, micropapillary pattern at the invasive front is associated with unresectable CRCs, and detection of it could help identify unresectable CRC cases.

Stromal invasion and micropapillary pattern in 212 consecutive surgically resected stage I lung adenocarcinomas: histopathological categories for prognosis prediction

Background and AimIt is of importance to search for prognostic indicators supplementing the tumour–node–metastasis stage for surgically resected early-stage lung adenocarcinomas. The roles of stromal invasion and micropapillary pattern in...

A petefészek serosus „borderline” tumorainak diagnosztikai nehézségei

About 15-20% of all ovarian neoplasms are of borderline type (or atypical proliferative or carcinoma of low malignant potential). They represent a common diagnostic and treatment problem both for the pathologist and for clinicians. The borderline tumors occur most commonly in childbearing age, show an indolent course and have good prognosis but are resistant to the traditional chemotherapies. The serous borderline tumors are the most common types of borderline ovarian tumors and they can cause differential diagnostic problems even for the experienced pathologist. We studied 30 cases which were diagnosed in our institute from 2000 to 2008. Thirteen were typical serous borderline tumors, in 7 cases the pattern was micropapillary, in 2 cases with microinvasion and in the remaining 8 cases the borderline tumors were associated with low-grade serous carcinomas. Seventeen of the 22 borderline cases were stage I tumors. There were noninvasive implants in the remaining 5 cases and in the cases of the low-grade carcinomas we could find, besides the noninvasive implants (in 3 cases), invasive implants or metastasis too. The main diagnostic problems in serous ovarian borderline tumors are the presence of micropapillary pattern, to detect microinvasion, or to differentiate the pseudo-borderline pattern of the low-grade serous tumors from a real borderline tumor and especially to diagnose the extraovarian diseases (types of implants). We discuss these diagnostic problems and criteria according to recent literature and our experience.

Prognostic significance of the micropapillary pattern in patients with serous borderline ovarian tumors

The impact of micropapillary histology on survival in patients with serous borderline ovarian tumors is not established. The purpose of this study was to evaluate the significance and influence of micropapillary pattern on clinical outcome of patients with serous borderline ovarian tumors. Eighty-five patients who underwent surgery and were diagnosed with serous borderline ovarian tumors were retrospectively studied. Among these patients, 18 patients showed micropapillary pattern on histologic examination, while the remaining 67 patients did not. The significance of the presence of micropapillary pattern and relationship with various clinicopathologic findings and progression-free survival were evaluated by statistical analysis. No differences with regard to age, parity, body mass index, pretreatment CA-125 level, tumor size, bilaterality, and the duration of follow-up were observed between the two groups, but there was a significant difference in terms of FIGO stage (p<0.001), invasive implants (p=0.004), performing lymphadenectomy (p=0.009), operation time (p=0.003), estimated blood loss (p<0.001), residual disease>1 cm (p=0.001), adjuvant chemotherapy (p<0.001), and the length of hospital stay (p=0.013). Progression-free survival was found to be significantly decreased in patients with invasive implants (HR, 5.06; p=0.025) and micropapillary pattern (HR, 4.20; p=0.056) on multivariate analysis. Micropapillary serous borderline ovarian tumors were associated with a more aggressive clinical course compared with typical serous borderline ovarian tumor. The presence of invasive implants and micropapillary pattern were significant prognostic factors in patients with serous borderline ovarian tumors.