Micropapillary pattern: a distinct pathological marker to subclassify tumours with a significantly poor prognosis within small peripheral lung adenocarcinoma (≤20 mm) with mixed bronchioloalveolar and invasive subtypes (Noguchi's type C tumours)

Makimoto, Yoshifumi; Nabeshima, Kazuki; Iwasaki, Hiroshi; Miyoshi, Tatsu; Enatsu, Sotarou; Shiraishi, Takeshi; Iwasaki, Atsushi; Shirakusa, Takayuki; Kikuchi, Megumi

doi:10.1111/j.1365-2559.2005.02126.x

Cited by 113 publications

(104 citation statements)

References 20 publications

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“…Interestingly, 63% of the patients in group IV that had micropapillary pattern in their tumors died of the disease, in comparison to 27% of patients with solid pattern, 14% with acinar, and 10% with papillary patterns. Although the number of death in this study population was small for statistical analysis of a specific histological pattern and prognosis, our data seem to support previous observations 13,14 that a micropapillary pattern seems to carry a worse prognosis than the other patterns of invasive adenocarcinoma.…”

Section: Survival Analysissupporting

confidence: 87%

Histologic features are important prognostic indicators in early stages lung adenocarcinomas

et al. 2007

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This study attempts to evaluate the clinicopathologic features of mixed subtype adenocarcinomas and the prognostic implications of histopathology classifications. Surgical specimens from 141 patients with clinical stage I or II lung adenocarcinoma during the period 1992-2004 were included. These cases were classified into four groups defined by the extent of the bronchioloalveolar carcinoma component: group I: pure bronchioloalveolar carcinoma; group II: mixed subtype with predominant bronchioloalveolar carcinoma component and r5 mm invasive component; group III: mixed subtype with bronchioloalveolar carcinoma component and 45 mm invasive component; group IV: invasive carcinoma with no bronchioloalveolar carcinoma component. Descriptive statistics were used to examine the groups with respect to age, tumor size, lymph node metastasis, and Ki-67 and p53 expression levels. Death rate for the groups was obtained by patient's charts and from the National Death Index database. The population was similar in age, tumor size and lymph node metastasis. Immunohistochemical results showed that the mean Ki-67 labeling and the amount of p53 overexpression had the same trend of increasing mean values or positive results from groups I to IV. The reported proportion of deaths ranged from 0% for groups I and II, 20% in patients with predominant invasive component with bronchioloalveolar carcinoma (group III), and 18% in patients with invasive carcinomas and no bronchioloalveolar carcinoma component (group IV). The difference between the proportion of patients with reported deaths in the time period of this study in the combined greater than 5 mm þ pure invasive groups (groups III, IV), and the o5 mm þ noninvasive groups (groups I, II) is statistically significant. These results suggest that histological features may be useful in defining categories of lung adenocarcinomas with differing survival and prognostic features. These results are helpful in defining a subcategory of 'minimally invasive adenocarcinoma', which has features similar to bronchioloalveolar carcinoma. Noguchi et al 2 looked at small lung adenocarcinomas measuring o2 cm, and defined six different categories including pure bronchioloalveolar carcinoma, bronchioloalveolar carcinoma with areas of fibroblastic foci due to structural collapse, bronchioloalveolar carcinoma with active fibroblastic proliferation, and different categories of invasive carcinoma. They showed that patients with tumors with a pure bronchioloalveolar carcinoma pattern had a 100% 5-year survival, patients with adenocarcinomas of mixed subtype with bronchioloalveolar carcinoma and invasive components had a 75% 5-year survival, while those patients with a purely invasive carcinoma had a 52% 5-year survival.

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Section: Survival Analysissupporting

confidence: 87%

Histologic features are important prognostic indicators in early stages lung adenocarcinomas

et al. 2007

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“…Micropapillary pattern is characterized by papillary structures with tufts lacking a central fibrovascular core. 12 Patients with micropapillary patternpositive lung adenocarcinomas have poor prognosis and tend to present with extensive lymph node involvement and metastatic disease, [12][13][14][15] similar to patients with micropapillary carcinomas of the breast, 23 urinary bladder, 24,25 ureter 26,27 and parotid gland. 28,29 However, little is known about the mechanisms involved in micropapillary patternassociated lymph node metastasis.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, cases of none and 1 þ were classified as micropapillary pattern-negative, whereas those of 2 þ and 3 þ as micropapillary pattern-positive as described previously. 15 This micropapillary pattern scoring was performed independently by two pathologists (TK and KN), and a high level of concordance (490%) was achieved. In case of disagreement, the slides were reviewed again to obtain a consensus view.…”

Section: Pathologic Evaluationmentioning

confidence: 99%

“…In contrast, lung adenocarcinomas with a micropapillary pattern have been reported to have a worse biological behavior, and that the patients with micropapillary pattern tend to present with advanced stage including lymph node metastasis. [12][13][14][15] In the present study, we investigated whether the stromal invasion grading system correlates with prognosis including pT1 (r3.0 cm) adenocarcinomas. Furthermore, we also tested whether the stromal invasion grade 3 could be subclassified into two groups that show significantly different prognoses based on the presence and absence of micropapillary pattern.…”

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confidence: 99%

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Micropapillary pattern and grade of stromal invasion in pT1 adenocarcinoma of the lung: usefulness as prognostic factors

et al. 2007

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Recently, the stromal invasion grading system was proposed for small adenocarcinomas of r2.0 cm. The system is based on the presence or absence of a fibrotic focus, and the extent of invasion into the fibrotic focus. Although stromal invasion grading system closely correlated with the prognosis, stromal invasion grade 3, representing stromal invasion into the center of a fibrotic focus, was the largest group of tumors and showed variable prognosis. In this study, we investigated whether stromal invasion grading system could be applied to and validated in pT1 adenocarcinomas as the TNM classification is the most universally used system. Furthermore, we investigated whether stromal invasion grade 3 cases could be subclassified according to the presence and absence of micropapillary pattern. The study included 120 cases of pT1 lung adenocarcinomas, of which 81 (68%) cases were stromal invasion grade 3. Micropapillary pattern was positive in 80% of grade 3 cases. For stromal invasion grade 3 cases, the 5-year survival rate of patients with micropapillary patternpositive carcinomas was 63%, which was significantly worse than 94% of those with micropapillary patternnegative carcinomas (P ¼ 0.0196). The latter was very close to that for patients with stromal invasion grade 0-2 (95%). Moreover, small cluster invasion was observed at sites of stromal invasion significantly more often in micropapillary pattern-positive cases than negative cases. Thus, the stromal invasion grading system is reproducible and correlates with prognosis even in pT1 lung adenocarcinomas. Moreover, among patients with stromal invasion grade 3 carcinomas, favorable prognosis is noted in micropapillary pattern-negative cases. The micropapillary pattern subclassification provides an advantage to the stromal invasion grading system and reconfirms the importance of micropapillary pattern as a prognostic marker. Our study is the first to point to the possible association of micropapillary pattern-positive carcinomas and small cluster invasion.

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“…The micropapillary pattern in lung adenocarcinoma is characterized by small papillary tufts lying in alveolar spaces or in spaces encased by connective tissues, with the tufts having no fibrovascular core, 18,19 and it has been reported as an important factor for poor prognosis. [18][19][20][21] However, the detailed histopathobiological features of the micropapillary pattern have not yet been clarified. We investigated the histological, immunohistochemical, electron microscopic, and clinicopathological properties of the micropapillary pattern to elucidate why it could be a factor in poor prognoses.…”

Section: Introductionmentioning

confidence: 99%

Histopathological features and prognostic significance of the micropapillary pattern in lung adenocarcinoma

et al. 2008

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The micropapillary pattern is characterized by small papillary tufts with no fibrovascular core lying in spaces and has been reported as an aggressive variant of carcinoma in several organs. We investigated the histopathobiological properties of the micropapillary pattern with immunohistochemistry, serial sections, and electron microscopy in lung adenocarcinoma. We further analyzed its clinicopathological character and prognosis. The subjects included 383 adenocarcinoma cases, of which 184 (48%) were micropapillary patternpositive and 199 (52%) were micropapillary pattern-negative. On histology, micropapillary tufts seemed to float in the alveolar space or spaces encased by connective tissues, whereas serial sections revealed that most tufts had continuity with other tufts and even with the main tumor. Positive staining for the adhesion molecules E-cadherin and b-catenin suggested the preservation of tight adhesion, and electron microscopy showed the existence of intercellular junctions. Negative staining for laminin and loss of basement membrane as determined by electron microscopy suggest a loss of cell-matrix contact. Positive staining for Ki-67 indicates that cells constituting micropapillary tufts retained their proliferation potency. There were no CD34-positive cells in micropapillary tufts, and the loss of the vascular core was confirmed. In micropapillary pattern-positive cases, lymphatic invasion was identified significantly more frequently than in micropapillary pattern-negative cases (Po0.001), even at stageIA (without lymph node metastasis, N ¼ 197) (Po0.001). The 5-year and 10-year overall survival rates of the micropapillary pattern-positive stageIA group were 77.6 and 67.6%, respectively, which were significantly less than those of the micropapillary pattern-negative stageIA group (98.1 and 98.1%) (P ¼ 0.001). In conclusion, cells constituting the micropapillary pattern are likely to have acquired anchorage-independent growth and a potential for high malignancy.

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Micropapillary pattern: a distinct pathological marker to subclassify tumours with a significantly poor prognosis within small peripheral lung adenocarcinoma (≤20 mm) with mixed bronchioloalveolar and invasive subtypes (Noguchi's type C tumours)

Abstract: MPP is a simple and distinct pathological marker to subclassify tumours with a significantly poor prognosis within small (

Cited by 113 publications

References 20 publications

Histologic features are important prognostic indicators in early stages lung adenocarcinomas

Histologic features are important prognostic indicators in early stages lung adenocarcinomas

Micropapillary pattern and grade of stromal invasion in pT1 adenocarcinoma of the lung: usefulness as prognostic factors

Histopathological features and prognostic significance of the micropapillary pattern in lung adenocarcinoma

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