Papillary Adenoma of the Lung in Asymptomatic Former Smoker Patient

diagnostics

Interesting Images Massive Relief: Papillary Adenoma of the Lung in Asymptomatic Former Smoker Patient

Jelena Stojšić 1,* , Marko Popović 2, Federica Pezzuto 3 and Jelena Marković 1

1 Department of Thoracic Pathology, Service of Pathology, University Clinical centre of Serbia, Pasterova 2, 11000 Belgrade, Serbia; [email protected] 2 Clinic of Thoracic Surgery, University Clinical Centre of Serbia, Koste Todorovi´ca26, 11000 Belgrade, Serbia; [email protected] 3 Department of Cardiac, Thoracic, Vascular Sciences and Public Health, Pathology Section, Medical School, University of Padova, 35121 Padova, Italy; [email protected] * Correspondence: [email protected]; Tel.: +381-69-17-47-680

Received: 9 October 2020; Accepted: 4 November 2020; Published: 6 November 2020

Abstract: Benign epithelial tumors of the lung are uncommon and can represent a diagnostic challenge. Herein, we describe one such emblematic case. A 59-year-old former smoker male was admitted to the hospital complaining of cough for a long time. A radiological examination showed a centrally excavated mass strictly connected to the visceral pleura. The patient underwent tumorectomy. At gross examination, the tumor was composed of solid and cystic areas containing clear liquid. Histological examination highlighted a sub-pleural encapsulated tumor, with foci of capsular invasion, characterized by a single layer of columnar and cuboidal epithelial cells lining moderately cellular fibro-vascular cores. A wide spectrum of immunohistochemical markers was performed. The final diagnosis was suggestive of a peripheral pulmonary papillary tumor of undetermined malignant potential. At the last follow-up, six years after surgery, no recurrence or metastases were described. Reporting this case, we would like to point out the existence of these rare entities that should be taken into account in the diagnostic process, thus avoiding potential misdiagnosis. Moreover, the presence of capsular invasion should be better investigated in order to reconsider the exact terminology of the tumor and the classification of its malignant potential.

Keywords: papillary tumor; papillary adenoma; peripheral tumor; lung; well-diﬀerentiated papillary mesothelioma; sclerosing hemangioma (pneumocytoma); alveolar adenoma

Diagnostics 2020, 10, 906; doi:10.3390/diagnostics10110906 www.mdpi.com/journal/diagnostics Diagnostics 2020, 10, 906 2 of 4 Diagnostics 2020, 10, x FOR PEER REVIEW 2 of 4

FigureFigure 1. 1.A A 59-year-old 59-year-old former smoker smoker male male patient patient was was admitted admitted to the to hospital the hospital for a persistent for a persistent dry drycough cough in in the the last last few few weeks. weeks. In In the the medical medical history, history, a atreated treated hypertensive hypertensive cardiomyopathy cardiomyopathy was was reported.reported. At At chest chest X-Ray x-ray aa nodulenodule ofof 9 cm in ma maximumximum diameter diameter was was revealed. revealed. A Achest chest CT CT scan scan was was alsoalso performed, performed, highlighting highlighting an an excavated excavated massmass that arose from from the the posterior posterior part part of of the the lower lower right right lobelobe visceral visceral pleura. pleura. Radiological Radiological examinationexamination ruledruled out out close close and and distant distant metastases. metastases. The The patient patient underwentunderwent thoracotomy thoracotomy with with tumorectomy tumorectomy withoutwithout pr previousevious biopsy. biopsy. At At surgery, surgery, the the tumor tumor appeared appeared encapsulatedencapsulated and and was was strictly strictly connected connected toto thethe visceralvisceral pleural, pleural, thus thus suggesting suggesting a mesothelial a mesothelial origin. origin. AtAt macroscopic macroscopic examination, examination, the the tumor tumor measuredmeasured 9.59.5 × 7 × 4.54.5 cm cm and and it itwas was composed composed of ofpapillary papillary × × solidsolid structures structures in in the the context context of of multicysticmulticystic spaces with with clear clear liquid liquid content content (A (,AB,).B ).Histologically, Histologically, lunglung samples samples showed showed a a subpleural subpleural lesion lesion surroundedsurrounded by a a fibrous fibrous pseudocapsule. pseudocapsule. The The neoplasia neoplasia was was characterizedcharacterized by by a a single single layer layer of of columnar columnar andand cuboidalcuboidal epithelial epithelial cells cells lining lining moderately moderately cellular cellular fibrovascularfibrovascular cores, cores, composed composedof ofplump, plump, homogeneoushomogeneous spindle spindle cells cells in in a astreaming streaming fashion, fashion, and and a a moderatemoderate lymphocytic lymphocytic infiltration. infiltration. TheThe lininglining epithelial cells cells demonstrated demonstrated minimal minimal cytological cytological and and nuclear atypia, with no mitotic figures. Neither tertiary structures, as branching of papillary fronds nuclear atypia, with no mitotic figures. Neither tertiary structures, as branching of papillary fronds without concomitant fibrovascular stromal, nor lepidic aspects were seen (C, haematoxylin and eosin, without concomitant fibrovascular stromal, nor lepidic aspects were seen (C, haematoxylin and eosin, original magnification, × 100). Microfoci of tumor invasion in the pseudocapsular tissue and visceral original magnification, 100). Microfoci of tumor invasion in the pseudocapsular tissue and visceral pleura were described.× The differential diagnosis included: sclerosing hemangioma, pulmonary pleura were described. The differential diagnosis included: sclerosing hemangioma, pulmonary papillary adenoma, papillary adenocarcinoma, and pseudoglandular carcinoid tumor. The diagnosis papillary adenoma, papillary adenocarcinoma, and pseudoglandular carcinoid tumor. The diagnosis of of pulmonary adenofibroma was also considered. pulmonary adenofibroma was also considered.

Pulmonary papillary adenoma is a rare neoplasm, predominantly occurring in peripheral lung areas, usually asymptomatic, that consists of cuboidal to columnar cells without nuclear pleomorphism and absent or low proliferative index. It mainly affects the male population, with an age range from 2 months to 70 years [1]. Pulmonary papillary adenomas of indeterminate malignant potential are described only in a few reports [2–4]. In these cases, although the clinical behavior has been demonstrated as benign, microfoci of invasion in the pseudocapsular tissue and visceral pleura suggested a local aggressiveness or a potential malignant behavior. More recently, a malignant transformation has also been reported, with the features of acinar and micropapillary adenocarcinoma within the mass [5]. Some differential diagnoses should be taken into consideration, such as differentiated papillary mesothelioma, sclerosing hemangioma (pneumocytoma), alveolar adenoma, and lung adenocarcinoma. Immunohistochemistry could be helpful in distinguishing these entities [6–10]. Depending on the localization and size of this tumor, surgical resection (wedge resection or lobectomy) is always the gold standard treatment [2,11]. The description of infiltrative borders, as also highlighted in our case, supports the need of reconsidering the definition of the tumor, replacing the term “pulmonary papillary adenoma” with “peripheral papillary tumor of undetermined malignant potential”. Further molecular investigations are mandatory to explore if this entity could be a step involved in the development of malignant forms.

Diagnostics 2020, 10, 906 3 of 4 Diagnostics 2020, 10, x FOR PEER REVIEW 3 of 4

FigureFigure 2. A Alarge large panel panel of antibodies of antibodies was performed. was performed. The epithelial The cells epithelial were positive cells were for TTF-1 positive (clone for TTF-18G7G3/1, (clone DAKO 8G7G3 Cytomation,/1, DAKO Glostr Cytomation,up, Denmark; Glostrup, dilution Denmark; 1:100) dilution (A), Napsin 1:100) A ( A(clone), Napsin IP64, A TM (cloneNovocastra IP64,TM Novocastra HD, Leica TMBiosystems,HD, Leica Newcas Biosystems,tle, UK; Newcastle,dilution 1:400) UK; (B dilution), Surfactant 1:400) B (Novacastra (B), Surfactant BHD (Novacastra Leica Biosystems,TM HD Leica Newcastle, Biosystems, UK; dilution Newcastle, 1:50) UK; (C dilution), Cytokeratin 1:50) ( C7 ),(clone Cytokeratin OV-TL 712/30, (clone DAKO OV-TL 12Cytomation,/30, DAKO Cytomation,Glostrup, Denmark; Glostrup, dilution Denmark; 1:100) dilution (D), 1:100)pancytokeratin (D), pancytokeratin (clone AE1/AE3, (clone AE1 DAKO/AE3, DAKOCytomation, Cytomation, Glostrup, Glostrup, Denmark; Denmark; dilution dilution 1;100) 1:100) (MNF-116) (MNF-116) (E) (andE) and negative negative for for Synaptophysin Synaptophysin (clone(clone 27G1, 27G1, Novocastra NovocastraTM TM HD, Leica Biosystems, Biosystems, Newcastle, Newcastle, UK UK;; dilution dilution 1:100) 1:100) and and Chromogranin Chromogranin AA (clone (clone 5H7,5H7,dilution dilution Cytomation,Cytomation, Glostrup,Glostrup, Denmark; dilution 1;100). 1:100). The The ne neuroendocrineuroendocrine tumor tumor didifferentiationfferentiation was was excluded. excluded. The The Ki-67 Ki-67 (clone (clone Ki-67P, Ki-67P, Novocastra NovocastraTM HD, LeicaTM HD, Biosystems, Leica Biosystems, Newcastle, UK;Newcastle, dilution UK; 1:100) dilution proliferative 1:100) proliferative index was <1% index (F), was suggesting <1% (F), a lowsuggesting rate of growtha low rate and of dismissing growth and the hypothesisdismissing ofthe a papillaryhypothesis adenocarcinoma. of a papillary Pneumocytomaadenocarcinoma. (so-called Pneumocytoma “sclerosing (so-called hemangioma”) “sclerosing was alsohemangioma”) ruled out based was on also the ruled lack of out sclerotic based stroma, on the foamy lack of histiocytes, sclerotic andstroma, hemosiderin foamy histiocytes, deposits and and the overallhemosiderin absence deposits of epithelial and the markers overall (TTF-1, absence Cytokeratin7, of epithelial MNF-116 markers and(TTF-1, Napsina Cytokeratin7, A) in the underlyingMNF-116 stroma.and Napsina Likewise, A) in the the abundance underlying of stroma. papillary Likewise structures, the and abundance the features of papillary of the stroma structures dismissed and the the diagnosisfeatures of of the a pulmonary stroma dismissed adenofibroma. the diagnosis The final of a pulmonary diagnosis was adenofibroma. in favor ofa The “peripheral final diagnosis pulmonary was papillaryin favor of tumor”. a “peripheral The invasive pulmonary behavior papillary of thetumor” tumor. The cells invasive with focibehavior of invasiveness of the tumor towards cells with the pericapsularfoci of invasiveness tissue suggested towards the the definition pericapsular of “undetermined tissue suggested malignant the definition potential”. of At“undetermined the last follow up,malignant six years potential”. after surgery, At the no last recurrence follow up, or metastasessix years after were surgery, reported no inrecurrence this patient. or metastases were reported in this patient.

Author Contributions: Conceptualization, J.S., J.M., and M.P.; formal analysis, J.S. and F.P., data curation, M.P., Pulmonary papillary adenoma is a rare neoplasm, predominantly occurring in peripheral lung M.P. writing—review and editing, J.S. and F.P.; supervision: J.S. All authors have read and agreed to the published versionareas, ofusually the manuscript. asymptomatic, that consists of cuboidal to columnar cells without nuclear Funding:pleomorphismThis research and absent received or nolow external proliferative funding. index. It mainly affects the male population, with an age range from 2 months to 70 years [1]. Pulmonary papillary adenomas of indeterminate malignant Acknowledgments: The authors want to thank to Fiorella Calabrese for her invaluable support given in preparation ofpotential this article. are described only in a few reports [2–4]. In these cases, although the clinical behavior has been demonstrated as benign, microfoci of invasion in the pseudocapsular tissue and visceral pleura Conflicts of Interest: The authors declare no conflict of interest. suggested a local aggressiveness or a potential malignant behavior. More recently, a malignant Consenttransformation for Publication: has alsoThe authorsbeen confirmreported, that with patient the agreed features for publication of acinar of this and case report.micropapillary adenocarcinoma within the mass [5]. Some differential diagnoses should be taken into consideration, Referencessuch as differentiated papillary mesothelioma, sclerosing hemangioma (pneumocytoma), alveolar 1.adenoma,Travis, and W.D.; lung Brambila, adenocarcinoma. E.; Burke, A.P.; Immunohistochemi Marx, A.; Nicholson,stry A.G.couldWHO be helpful Classification in distinguishing of Tumoursof these Lung, entitiesPleura, [6–10]. Thymus Depending and Heart, 4thon ed.;the Internationallocalization Agency and size for Researchof this tumor, on Cancer surgical (IARC): resection Lyon, France, (wedge 2015. 2.resectionCornejo, or lobectomy) K.M.; Shi, M.; isAkalin, always A.; the Uy, gold K.; Cagle,standa P.T.;rd treatment Fraire, A.E. [2,11]. Pulmonary The de papillaryscription adenoma: of infiltrative A case borders,report as and also review highlighted of the literature. in our J.case, Bronchol support Intervs Pulmonol.the need 2013of reconsidering, 20, 52–57. [CrossRef the definition][PubMed of] the tumor, replacing the term “pulmonary papillary adenoma” with “peripheral papillary tumor of

Diagnostics 2020, 10, 906 4 of 4

3. Mori, M.; Chiba, R.; Tezuka, F.; Kaji, M.; Kobubo, T.; Nukiwa, T.; Takahashi, T. Papillary adenoma of type II pneumocytes might have malignant potential. Virchows Arch. 1996, 428, 195–200. [CrossRef][PubMed] 4. Dessy, E.; Braidotti, P.; Del Curto, B.; Falleni, M.; Coggi, G.; Santa Cruz, G.; Carai, A.; Versace, R.; Pietra, G.G. Peripheral papillary tumor of type-II pneumocytes: A rare neoplasm of undetermined malignant potential. Virchows Arch. 2000, 436, 289–295. [CrossRef][PubMed] 5. Ma, H.; Wang, Y.; Chen, P.; Zhang, Z.; Xu, J. Pulmonary papillary adenoma with malignant transformation: Report of one case and review of the literature. Int. J. Clin. Exp. Pathol. 2020, 13, 792–798. [PubMed] 6. Stojsić,J.; Milenković,V.; Radojicić,J.; Percinkovski, M. Pulmonary sclerosing haemangioma—Case report. Srp. Arh. Celok. Lek. 2007, 135, 569–571. 7. Suzuki, H.; Saitoh, Y.; Koh, E.; Hoshino, H.; Kase, D.; Kasei, Y.; Azuhata, Y.; Kishi, H.; Hiroshima, K.; Sekine, Y. Pulmonary sclerosing hemangioma with pleural dissemination: Report of a case. Surg. Today 2011, 41, 258–261. [CrossRef][PubMed] 8. Ichinose, J.; Nakahara, K.; Kina, S.; Miyanaga, S. A case of sclerosing hemangioma forming a pedunculated mass. Ann. Thorac. Cardiovasc. Surg. 2011, 17, 408–410. [CrossRef][PubMed] 9. Stojsić,J.; Milenković,B.; Radojicić,J.; Percinkovski, M. Alveolar adenoma—A rare lung tumour. Srp. Arh. Celok. Lek. 2007, 135, 461–464. 10. Mori, M.; Tezuka, F.; Chiba, R.; Funae, Y.; Watanabe, M.; Nukiwa, T.; Takahashi, T. Atypical adenomatous hyperplasia and adenocarcinoma of the human lung: Their heterology in form and analogy in immunohistochemical characteristics. Cancer 1996, 77, 665–674. [CrossRef] 11. Lin, X.Y.; Han, Q.; Wang, E.H.; Zhang, Y. Pulmonary papillary adenoma presenting in central portion: A case report. Diagn. Pathol. 2015, 10, 190. [CrossRef][PubMed]

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional aﬃliations.

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).