Hypercalcemia with invasive pulmonary papillomatosis and microinvasive squamous carcinoma

Abstract

Juvenile respiratory papillomatosis is a rare pediatric disease in which benign papillomata develop in the respiratory tract, most commonly involving the larynx and tracheobronchial tree. Invasive pulmonary papillomatosis is an aggressive form in which the papillomata extend into the lung parenchyma. We report a case of a 22-year-old man with a long-standing juvenile respiratory tract papillomatosis, initially diagnosed at age 2, who subsequently developed invasive pulmonary papillomatosis and underwent partial surgical resection for his pulmonary disease. Hypercalcemia complicated the patient’s final hospitalizations. HPV typing performed on a laryngeal papilloma was positive for HPV 6/11. The lobectomy specimen revealed malignant transformation of invasive pulmonary papillomatosis characterized by the presence of microinvasive nests of squamous carcinoma. Immunohistochemical stain for parathyroid hormone on the invasive component was negative. Eventually, the patient succumbed to his disease and while the family refused post-mortem examination, Positron Emission Tomography (PET) performed during the patient’s terminal course suggested the possibility of metastasis to liver and periaortic lymph nodes. There was no evidence of bony metastasis.

Keywords

Invasive pulmonary papillomatosis / Recurrent respiratory papillomatosis / Juvenile respiratory papillomatosis / Pulmonary papillomatosis hypercalcemia / Paraneoplastic syndrome / Invasive pulmonary papillomatosis and squamous cell carcinoma

CONFLICTS OF INTEREST DISCLOSURE

We declare that we have no conflict interests.

References

[1] Kerly SW, Buchon-Zalles C, Moran J, et al. Chronic Cavitary Respiratory Papillomatosis. Arch Pathol Lab Med. 1989; 113: 1166-1169.

[2] Siddiqi T, Assar S, Lougee K, et al. Malignant transformation of recurrent respiratory papillomatosis: atypical presentation as right mainstem bronchus occlusion. Chest Journal. 2014; 145 (3): Supplement, 478A. https://doi.org/10.1378/chest.1836553

[3] Xiao Y, Wang J, Han D, et al. A case of intrapulmonary spread of recurrent respiratory papillomatosis with malignant transformation. Am J Med Sci. 2015; 350 (1): 55-57. PMid:25423295. https://doi.org/10.1097/MAJ.0000000000000370

[4] Gerein V, Rastorgnev E, Gerein J. Incidence, age at onset, and potential reasons of malignant transformation in recurrent respiratory papillomatosis patients: 20 years experience. Otolaryngology Head and Neck Surgery. 2005; 132: 392-394. PMid:15746849. https://doi.org/10.1016/j.otohns.2004.09.035

[5] Rady PL, Schnadig VJ, Weiss RL, et al. Malignant transformation of recurrent respiratory papillomatosis associated with integrated human papilloma virus type 11 DNA and mutation of p53. The Laryngoscope. 1998; 108 (5): 735-740. PMid:9591556. https://doi.org/10.1097/00005537-199805000-00021

[6] Orphanidou D, Dimakou K, Latsi P, et al. Recurrent respiratory papillomatosis with malignant transformation in a young adult. Respiratory Medicine. 1996; 90: 53-55. https://doi.org/10.1016/S0954-6111(96)90245-0

[7] Hammoud D, El Haddad B, Squamous cell carcinoma of the lungs arising in recurrent respiratory papillomatosis. Respiratory Medicine CME. 2010: 270-272. https://doi.org/10.1016/j.rmedc.2009.09.021

[8] Mitsumoto GL, Del Carlo Bernardi F, Paes JF, et al. Juvenile-onset recurrent respiratory papillomatosis with pulmonary involvement and carcinomatous transformation. Autopsy Case Reports. 2018; 8(3): e2018035. PMid:30101139. https://doi.org/10.4322.acr.2018.035

[9] Boudjemaa S, Leboulanger N, Dainese L, et al. Metastatic squamous cell carcinoma of the lung arising in a 12-year-old boy with juvenile recurrent respiratory papillomatosis of neonatal onset. Tuk Patholoji Derg. 2014; 30: 133-136. https://doi.org/10.5146/tjpath.2014.01238

[10] Solomon D, Smith RRL, Kashima HK, et al. Malignant transformation in Non-irradiated recurrent respiratory papillomatosis. Laryngoscope. 1985; 95 (8): 900-904. PMid:4021682. https://doi.org/10.1288/00005537-198508000-00003

[11] Cook JR, Hill A, Humphrey PA, et al. Squamous cell carcinoma arising in recurrent respiratory papillomatosis with pulmonary involvement: emerging common pattern of clinical features and human papilloma virus serotype associated. Mod Pathol. 2000; 13(8): 914-918 PMid:10955460. https://doi.org/10.1038/modpathol.3880164

[12] Davidson LA, Black M, Carey FA, et al. Lung tumors immunoreactive for parathyroid hormone related peptide: analysis of serum calcium levels and tumor type. J of Pathology. 1996; 178: 398-401. https://doi.org/10.1002/(SICI)1096-9896(199604)178:4＜398::AID-PATH496＞3.0.CO;2-G

[13] Schnadig V, Clark W, Clegg T, et al. Invasive papillomatosis and squamous carcinoma complicating juvenile laryngeal papillomatosis. Arch Otolaryngol Head Neck Surg. 1986; 112: 966-971 PMid:3741663. https://doi.org/10.1001/archotol.1986.03780090062011

[14] Guillou L, Sahli R, Chaubert P, et al. Squamous cell carcinoma of the lung in a nonsmoking, non-irritated patient with juvenile laryngotracheal papillomatosis. Am J Surg Path. 1991; 15: 891-898 PMid:1659237. https://doi.org/10.1097/00000478-199109000-00010

[15] Sakakura A, Yamamoto Y, Takasaki T, et al. Recurrent laryngeal papillomatosis developing into laryngeal carcinoma with human papilloma virus (HPV) type 18:A case report. J Laryngol Otol. 1996; 110: 75-77. PMid:8745789. https://doi.org/10.1017/S0022215100132773

[16] Doyle DJ, Gianoli GJ, Espinola T, et al. Changes in human papilloma virus typing in recurrent respiratory papillomatosis progressing to malignant neoplasm. Arch Otolaryngology Head Neck Surgery. 1994; 120: 1273-1276. PMid:7917213. https://doi.org/10.1001/archotol.1994.01880350079014

[17] Lele S, Pou A, Ventura K, et al. Molecular events in the progression of recurrent respiratory papillomatosis to carcinoma. Arch Pathol Lab Med. 2002; 126: 1184-1188.