Chng Kiat Soon, Jason¹, Francis Yap Hong Xin¹

1. Department of Anatomical Pathology, Singapore General Hospital

Introduction and Case Details: A middle-aged non-smoker male with recurrent, chronic loculated left hydropneumothorax and a clinical impression of a left empyema underwent a left pleural peel as part of planned decortication. The specimen was grossly received as mixed fibrous and haemorrhagic tissue, and 10mls of blood-stained fluid was also obtained.
Microscopic Appearance: Predominant mixed acute and chronic inflammation was identified with organising fibrinous pleuritis. Focal areas contained abundant neutrophilic infiltrate with fibrin and haemorrhage, consistent with abscess formation, as well as transition to areas of organisation with fibroblastic proliferation and scattered plasma cells was present. Focal areas showed squamous epithelium admixed with fibrous tissue, containing a basal layer and showing evidence of maturation, but without evidence of keratinisation or associated adnexal structures. Focal reactive atypia was present in the squamous epithelium, but without evidence of dysplasia or malignancy. The squamous epithelial cells showed immunopositivity for D2-40, and was immunonegative for calretinin, WT-1 and p53.
Discussion: Mature squamous metaplasia of the pleura is exceedingly rare, with only one case reported by Kim et al. in 1995 related to pulmonary tuberculosis¹. Several cases of primary pleural squamous cell carcinoma (PPSCC) have been associated with pulmonary tuberculosis and bronchopleural fistulas^2,3. A similar process has also been observed in the peritoneal cavity, often following surgery or chronic irritation from bowel perforation. No cases of isolated squamous metaplasia of the pleura have been otherwise identified in isolation.

The pathogenesis remains elusive due to its rarity, but it is thought to result from chronic inflammation caused by irritation, which may prompt multipotent subserosal cells to differentiate into metaplastic squamous epithelium. This might represent a precursor in the development of PPSCC, in the context of ongoing inflammation. Key distinguishing features which support pleural squamous metaplasia over PPSCC include the absence of nuclear atypia, mitoses, necrosis, and a desmoplastic stromal response. Immunohistochemistry may be useful in challenging cases to elucidate the squamous nature of the epithelium (expected positivity for cytokeratin 7, high molecular weight cytokeratins, p40 and p63), and mesothelial origin (positivity for WT-1, D2-40 and calretinin).
Conclusion: Clinical and radiological findings are crucial for excluding extrapulmonary metastasis of squamous cell carcinoma and malignant mesothelioma. Increased awareness and further research are essential to better understand its connection to the development of PPSCC.

References:
1. Kim HJ; Lee JH; Ko GH. Squamous Metaplasia of the Pleura. Journal of Pathology and Translational Medicine. 1995;29:792-3.

2. Willén R, Bruce T, Dahlström G, Dubiel WT. Squamous epithelial cancer in metaplastic pleura following extrapleural pneumothorax for pulmonary tuberculosis. Virchows Arch A Pathol Anat Histol. 1976;370(3):225-31.

3.Prabhakar G, Mitchell IM, Guha T, Norton R. Squamous cell carcinoma of the pleura following bronchopleural fistula. Thorax. 1989;44(12):1053-4.