25-YEAR OLD MALE WITH PLEURAL THICKENING Case Report

The growth of some of the adenocarcinomas is virtually identical to that of ma- lignant mesothelioma, also known as pseudomesotheliomatous adenocarcinoma of lung. Their differentiation on the basis of histopathology can pose diagnostic dif-ﬁ culties; hence immunohistochemistry and electron microscopy may be required for further differentiation.


INTRODUCTION
Pseudomesotheliomatous adenocarcinoma is an uncommon variant of peripheral adenocarcinoma fi rst described by Harwood et al in 1976. It usually presents with signs of pleural thickening. Hence it may be a diagnostic challenge in patients in whom malignancy is least suspected. Further, even if a diagnosis of malignancy is made on histopathology, it may be confused with epithelial variety of mesothelioma. This case is being reported to emphasize the presence of this entity and modalities which can be used to make the exact diagnosis.  A 25-year-old, non-smoker, male presented with dull aching left sided chest pain, dry cough and exertional dyspnoea for past two months. He was being treated with antituberculosis drugs over past two months for left sided pleural effusion. He denied history of exposure to organic or inorganic dust. There was no evidence of digital clubbing or lymphadenopathy. Examination was unremarkable except loss of volume, dull note and decreased auscultatory sounds over entire left hemithorax. Chest radiograph  2 But its occurrence in third decade of life in HIV negative patient as seen in our case is rare. Other differential diagnoses for pleural based mass with diffuse pleural thickening include solitary fi brous tumor of pleura, malignant mesothelioma, soft tissue sarcomas, malignant fi brous histiocytoma, fi bromyxoma, metastatic spindle cell carcinoma of lung and kidney, pseudomesotheliomatous angiosarcoma.

CASE HISTORY
Distinction between pseudomesotheliomatous adenocarcinoma and epithelial variety of mesothelioma may be diffi cult. Histochemical stains, immunohistochemical markers and electron microscopy can facilitate the distinction between the two. Histochemical stains include Periodic acid Schiff stain after diastase digestion (PAS-D) and Alcian blue stains. PAS-D stains neutral mucin, which is produced by adenocarcinomas. Alcian blue stains acid mucin that is produced by epithelial mesotheliomas. Further, immunohistochemical staining can be done to differentiate between the two. Adenocarcinomas immunoreact with glycoproteins (epithelial markers) like CEA, Ber EP4, B72.3, Cluster of differentiation (CD) 15, and BG-8 whereas mesotheliomas do not react with glycoproteins. Mesotheliomas show a thick, brush border like staining pattern with HBME-1 while adenocarcinoma do not stain with HBME-1 or show a cytoplasmic or thin membrane pattern of staining 3 . Currently there is no immunohistochemical stain, which is consistently positive in mesotheliomas and negative in adenocarcinomas, for example-CK and EMA are expressed in both the tumors. Thus, while adenocarcinoma can be diagnosed by positive staining for of the CEA, CD-15, Ber EP4 or B72.3, the immunohistochemical diagnosis of mesothelioma is one of exclusion 4 . Recently, Ordonez et al have recommend a panel of four markers for mesothelioma (two positive and two negative) from calretinin, cytokeratin5/6 or WT1 for the positive markers and CEA, MOC-31, B72.3, Ber-EP4 or BG-8 for negative markers. 5 Electron microscopy can also help in distinction; adenocarcinomas have short and thick microvilli as compared to mesotheliomas, which have very long, thin microvilli. 6 Our patient was referred to oncology for further management. Chemotherapy has an established role in the therapy of Stage-3b non-small cell lung carcinoma; randomized clinical trial data demonstrate improved median and long term survival when antineoplastic agents are used as part of multimodality approach. However, the optimal left sided diffuse pleural thickening and large soft tissue mass arising from thoracic and mediastinal pleura. No hilar or mediastinal lymphadenopathy was seen. Pleural fl uid analysis showed an exudate, negative for malignant cells, bacteria, fungi and mycobacteria. Ultrasonography of abdomen and bone scan was normal. CT guided biopsy of the pleural mass under high power fi eld is shown in fi g. 3.

Fig 3 : Histopathological examination of the biopsy specimen showing tumor cells in sheets and glandular arrangement with hyperchromatic nuclei (Haematoxylin and eosin, X 40).
Histopathological examination of the biopsy specimen shows (fi g 3) tumor cells arranged in papillary fronds, sheets and glandular structures with hyperchromatic nuclei suggestive of either adenocarcinoma or epitheloid variety of mesothelioma. Further, immunohistochemical markers were done to establish the diagnosis. Our biopsy specimen showed diffuse positivity for cytokeratin (CK) and epithelial membrane antigen (EMA), fluffy positivity for Carcinoembryonic antigen (CEA) and thin membrane positivity for mesothelial antigen-HBME-1, thus favoring the diagnosis of adenocarcinoma.

Diagnosis
Peripheral adenocarcinoma of the lung with extensive pleural involvement also called as pseudomesotheliomatous adenocarcinoma of the lung (stage -3b).

DISCUSSION
Peripheral adenocarcinoma typically manifests as a nodule with retraction of overlying pleura and an expansile growth pattern that destroys and displaces adjacent lung parenchyma. The borders of tumor may be rounded, lobulated, or poorly defi ned. The lobulation refl ects the histological heterogeneity of lung cancer whereas illdefi ned borders may be related to invasion of adjacent lung, fi brosis or interstitial oedema. The growth of some these adenocarcinomas are virtually identical to that of malignant mesothelioma, also known as pseudomesotheliomatous sequence for various modalities and best chemotherapy regimen remains to be defi ned. 7