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      Stromal micropapillary predominant lung adenocarcinoma: A rare histological phenotype with poor prognosis

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          Abstract

          An extremely rare case of stromal micropapillary predominant lung adenocarcinoma is presented in this study. A 70‐year‐old woman visited our hospital because of an abnormal shadow on chest X‐ray. Chest computed tomography revealed a nodule in the left lower lobe and a mass in the left upper lobe. She underwent an exploratory thoracotomy owing to the suspicion of advanced lung cancer. Pathological examination of the left lower lobe nodule revealed tumour cells with more than half the tumour cells showing stromal micropapillary pattern ( SMP), consisting of tumour cells invading the fibrotic stroma. In general, micropapillary adenocarcinomas in the lung form an aerogenous micropapillary pattern ( AMP), in which tumour cells float in alveolar spaces. Because the prognosis of SMP lung adenocarcinomas is known to be worse than that of AMP lung adenocarcinomas and have a high frequency of epidermal growth factor receptor mutations, the discrimination of SMP from AMP is important for both pathologists and clinicians.

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

          Taketo Yamada, M Kawamura, M Watanabe … (2008)
          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 pattern-positive 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 beta-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 (P<0.001), even at stageIA (without lymph node metastasis, N=197) (P<0.001). 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=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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            Stromal micropapillary component as a novel unfavorable prognostic factor of lung adenocarcinoma

            Miki Ohe, TOMOYUKI YOKOSE, Yuji Sakuma … (2012)
            Background Pulmonary adenocarcinomas with a micropapillary component having small papillary tufts and lacking a central fibrovascular core are thought to result in poor prognosis. However, the component consists of tumor cells often floating within alveolar spaces (aerogenous micropapillary component [AMPC]) rather than invading fibrotic stroma observed in other organs like breast (stromal invasive micropapillary component [SMPC]). We previously observed cases of lung adenocarcinoma with predominant SMPC that was associated with micropapillary growth of tumors in fibrotic stroma observed in other organs. We evaluated the incidence and clinicopathological characteristics of SMPC in lung adenocarcinoma cases. Patients and Methods We investigated the clinicopathological characteristics and prognostic significance of SMPC in lung adenocarcinoma cases by reviewing 559 patients who had undergone surgical resection. We examined the SMPC by performing immunohistochemical analysis with 17 antibodies and by genetic analysis with epidermal growth factor receptor (EGFR) and KRAS mutations. Results SMPC-positive (SMPC(+)) tumors were observed in 19 cases (3.4%). The presence of SMPC was significantly associated with tumor size, advanced-stage disease, lymph node metastasis, pleural invasion, lymphatic invasion, and vascular invasion. Patients with SMPC(+) tumors had significantly poorer outcomes than those with SMPC-negative tumors. Multivariate analysis revealed that SMPC was a significant independent prognostic factor of lung adenocarcinoma, especially for disease-free survival of pathological stage I patients (p = 0.035). SMPC showed significantly higher expression of E-cadherin and lower expression of CD44 than the corresponding expression levels shown by AMPC and showed lower surfactant apoprotein A and phospho-c-Met expression level than corresponding expression levels shown by tumor cell components without a micropapillary component. Fourteen cases with SMPC(+) tumors (74%) showed EGFR mutations, and none of them showed KRAS mutations. Conclusions SMPC(+) tumors are rare, but they may be associated with a poor prognosis and have different phenotypic and genotypic characteristics from those of AMPC(+) tumors. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9433341526290040.
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              Lung adenocarcinoma with a micropapillary pattern: a clinicopathological study of 25 cases.

              K Mizuno, N Kuroda, T Hirouchi … (2006)
              Lung adenocarcinoma with a micropapillary pattern has recently been described, but its biological behavior is as yet uncertain. In this article we present a clinicopathological study of lung adenocarcinoma with micropapillary morphology. We selected 25 patients with lung adenocarcinoma with micropapillary morphology from the 2001-2004 pathology files (age range 54 to 81 years; mean 64.5 years). Micropapillary carcinoma is predominantly located at the periphery of the tumor nodule or mass and occurs irrespective of the subtype of the adenocarcinoma. A micropapillary component was seen against a mucinous background in three cases and microcalcifications resembling psammoma bodies were seen in one case. Four cases showed intensive invasive growth such as micropapillary adenocarcinoma of the breast and 21 showed alveolar type morphology with piling-up of the neoplastic cells with or without stromal invasion. Seven of twenty-three (30.4%) showed lymph node metastases at time of operation. Twelve of twenty-five (48%) showed pleural invasion. Regarding clinical outcome, 14 patients were alive without disease, 5 were alive with disease, and 5 died of the lung adenocarcinoma. No significant relationship was found between the extent of the micropapillary component and prognosis. However, the carcinoma seen in the five patients who died showed breast type histology with intensive invasive growth in three cases and alveolar type histology with intensive stromal invasion in two. Lung micropapillary carcinoma of breast type may behave more aggressively than the alveolar type.
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                Author and article information

                Contributors
                Shogo Tajima: ssttssjp2@yahoo.co.jp
                Journal
                Journal ID (nlm-ta): Respirol Case Rep
                Journal ID (iso-abbrev): Respirol Case Rep
                Journal ID (doi): 10.1002/(ISSN)2051-3380
                Journal ID (publisher-id): RCR2
                Title: Respirology Case Reports
                Publisher: John Wiley & Sons, Ltd (Chichester, UK )
                ISSN (Electronic): 2051-3380
                Publication date (Electronic): 08 November 2016
                Publication date Collection: November 2016
                Volume: 4
                Issue: 6 ( doiID: 10.1002/rcr2.v4.6 )
                Electronic Location Identifier: e00203
                Affiliations
                [ 1 ] Department of Thoracic SurgeryFujieda Municipal General Hospital FujiedaJapan
                [ 2 ] Department of PathologyFujieda Municipal General Hospital FujiedaJapan
                [ 3 ] Department of RespiratoryFujieda Municipal General Hospital FujiedaJapan
                [ 4 ] Department of Surgery 1Hamamatsu University School of Medicine HamamatsuJapan
                Author notes
                [*] [* ] Correspondence

                Shogo Tajima, Department of Pathology, Fujieda Municipal General Hospital, 4‐1‐11 Surugadai, Fujieda, Shizuoka 426‐0077, Japan. E‐mail: ssttssjp2@ 123456yahoo.co.jp

                Article
                Publisher ID: RCR2203 Other ID: RCR-16-062.R1
                DOI: 10.1002/rcr2.203
                PMC ID: 5167289
                SO-VID: 1aa862c2-2343-48d1-9428-1e8a91a223ea
                Copyright © © 2016 The Authors. Respirology Case Reports published by John Wiley & Sons Australia, Ltd on behalf of The Asian Pacific Society of Respirology
                License:

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                Date received : 17 August 2016
                Date revision received : 28 September 2016
                Date accepted : 11 October 2016
                Page count
                Figures: 3, Tables: 0, Pages: 4, Words: 1594
                Categories
                Subject: Case Report
                Subject: Case Reports
                Custom metadata
                source-schema-version-number 2.0
                component-id rcr2202
                header-id rcr2203-hdr-0001
                cover-date November 2016
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_NLMPMC version:5.0.0 mode:remove_FC converted:19.12.2016

                Keywords: egfr mutation,lung adenocarcinoma,poor prognosis,stromal micropapillary pattern
                Data availability:
                Keywords: egfr mutation, lung adenocarcinoma, poor prognosis, stromal micropapillary pattern

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