Update on Pulmonary Ossifications in the Differential Diagnosis of Solitary Pulmonary Nodules

Abstract

Pulmonary ossifications have often been regarded as rare, post-mortem findings without any clinical significance. We have investigated the occurrence of pulmonary ossifications in patients undergoing thoracic procedures, and how this may affect the differential diagnosis of solitary pulmonary nodules. In addition, we have performed a literature search on the occurrence and possible pathogenesis of these ossifications. From January 2008 until August 2019, we identified pulmonary ossifications in 34 patients who underwent elective pulmonary surgery. Pre-operative imaging was unable to differentiate these ossifications from solid tumors. A definitive diagnosis was made by an experienced pathologist (VS, ML). The PubMed database was researched in December 2019 with the search terms “pulmonary ossifications”; “heterotopic ossifications”; and “solitary pulmonary nodule”. In total, 27 patients were male, with a mean age of 63 ± 12 years (age 41 to 82 on diagnosis). All lesions were identified on thoracic CT and marked for resection by a multidisciplinary team. A total of 17 patients were diagnosed with malignancy concurrent with ossifications. There was a clear predilection for the right lower lobe (12 cases, 35.3%) and most ossifications had a nodular form (70.6%). We could not identify a clear association with any other pathology, either cancerous or non-cancerous in origin. Oncologic or pulmonary comorbidities did not influence patient survival. Pulmonary ossifications are not as seldom as thought and are not just a curiosity finding by pathologists. These formations may be mistaken for a malignant space-occupying lesion, both pre-and perioperatively, as they are indistinguishable in imaging. We propose these ossifications as an underestimated addition to the differential diagnosis of a solitary pulmonary nodule.

A rare case and review of pulmonary ossification

“…A typical differential profile for NPO includes silicotic nodules, infectious granulomas, sarcoidosis, variola pneumonias, or carcinomas [ 1 , 3 , 24 ]. In contrast, DPO on CT demonstrates a branching, coral-like, dendriform pattern that is similar to features of bronchiectasis, pulmonary fibrosis, emphysema, and lymphangitic metastasis [ 23 , 25 ]. More common conditions such as interstitial lung disease, amyloidosis, histoplasmosis, prior tuberculosis, or granulomatosis with polyangiitis should be considered as differential diagnoses for DPO [ 26 ].…”

Proceedings of the 2022 National Toxicology Program Satellite Symposium

“…Dendriform pulmonary ossification can be idiopathic or associated with several conditions, including usual interstitial pneumonia, chronic obstructive pulmonary disease, pneumoconiosis, chronic gastroesophageal reflux disease, end-stage renal disease, and genetic mutations. [55][56][57][58][59][60]63,65 DPO has been reported in coyotes with pneumoconiosis, a dog with multiple mammary tumors, and a dog treated with exogenous cortisol. 61,62,64 An overt cause of pulmonary ossification was not identified in this case.…”

“…DPO is typically diagnosed as an incidental finding on postmortem examination, although pneumothorax may occur due to pleural rupture. [55][56][57][58][59][60][61][62][63][64][65] Two histologic subtypes of DPO are described in humans: nodular and dendriform.…”

“…These cases are often associated with mitral valve stenosis and other causes of chronic pulmonary congestion. 57,58 Patients with dendriform pulmonary ossification have spicules of metaplastic bone within alveolar septa which often contain bone marrow. [55][56][57][58]65 Histologic features of the presented case were most consistent with dendriform pulmonary ossification as opposed to nodular pulmonary ossification.…”

“…57,58 Patients with dendriform pulmonary ossification have spicules of metaplastic bone within alveolar septa which often contain bone marrow. [55][56][57][58]65 Histologic features of the presented case were most consistent with dendriform pulmonary ossification as opposed to nodular pulmonary ossification. Dendriform pulmonary ossification can be idiopathic or associated with several conditions, including usual interstitial pneumonia, chronic obstructive pulmonary disease, pneumoconiosis, chronic gastroesophageal reflux disease, end-stage renal disease, and genetic mutations.…”