A 61-year-old male patient who had marked volume loss in the right lung radiologically was admitted. Fiberoptic bronchoscopy was performed, an endobronchial lesion arising from the right upper lobe bronchus and nearly completely obstructing the right main bronchus was detected and multiple biopsies were taken. Histopathological examination of these biopsies confirmed a non-small cell carcinoma with osteoclast-like multinuclear giant cells. A sleeve upper lobectomy was performed through a right thoracotomy. Histopathological examination of the specimen showed “poorly differentiated squamous cell carcinoma and osteoclast-like multinuclear giant cells within”. The patient is well and disease-free 42 months after the operation.
There are numerous cases of osteoclast-like giant cells reported within the breast, thyroid, liver, gall bladder, stomach, pancreas, urinary bladder and endometrium but they are very rare within lung carcinomas. A diagnosis of lung carcinoma with osteoclast-like giant cells is very important as it may cause diagnostic confusion with giant cell carcinomas and foreign body type stromal reactions.
Macroscopic examination of the 15x8x5 cm sleeve upper lobectomy material displayed an endobronchial tumor 2.4 cm in diameter in the lumen of upper lobe bronchus infiltrating the bronchial wall. Histopathological examination of the tumor showed “poorly differentiated squamous cell carcinoma and osteoclast-like multinuclear giant cells within” (Figure 2). Immunohistochemical studies demonstrated expression of high molecular weight keratin, cytokeratin5/6, CEA, EMA and pancytokeratin in tumor cells. While OLGCs showed expression of vimentin and CD68, staining with CEA, EMA, pancytokeratin, CD45, actin, desmin, S-100 protein or calretinin were not observed. We found marked angiogenesis in the stroma around the OLGCs. The vascular proliferation was highligtened by strong immunohistochemical expression with CD34 and CD31 (Figure 3).
Figure 3: Marked angiogenesis demonstrated with CD31 among osteoclast like giant cells (x200).
We also think that some diagnostic problems may be experienced with those tumors. Foreign body type stromal reactions also contain giant cells. The differential diagnosis is usually obvious in resected specimens. However, small biopsies may be difficult to interpret and fine needle aspirates may be confusing. Immunohistochemistry may be helpful in these circumstances. We performed immunohistochemistry after the diagnosis of squamous cell carcinoma and observed expression with epithelial markers in tumor cells and strong positivity with histiocytic markers in OLGCs.
The largest series was from Bocklage et al. in 1998 consisting 3 carcinoma cases. They reported 1 adenocarcinoma and 2 sarcomatoid carcinomas and discussed the host reaction and possible mechanisms that may stimulate OLGC response[4]. They said that osteoclastic differentiation from monocyte/macrophage bone marrow precursor cells and peripheral blood monocytes is a complex process that involves a host of soluble mediators as well as cell contact with osteoblasts.
Agnantis et al. discussed the angiogenesis in those tumors and underlined that the observation that the giant cells generally occurred in areas of prominent angiogenesis suggests that angiogenesis may be induced by some chemical substancs produced by the tumor cells[5]. In our case, we observed marked angiogenesis in the stroma surrounding OCLGCs too. Strong immunochemical staining with CD31 and CD34 showed prominent vascular proliferation.
In Leung and Morava-Protzner’s study, immunohistochemical stains demonstrated that the giant cells were of monocytic/histiocytic origin probably representing a distinctive host response to the tumor[3]. Our immunohistochemistry study results, including strong positivity with CD68 and negativity with epithelial markers also confirmed that OLGCs were of histiocytic origin.
Our patient is well and disease free 42 months after the resection. Although it is difficult to comment on the prognosis of lung carcinomas with OLGCs for now since they are very rare, it is said that those cells indicate good prognostic factor in other system malignancies with similar findings[6-8]. Further studies are needed to comment on the prognosis of lung carcinomas with OLGCs.
This is the seventh published report of lung carcinoma with osteoclast-like giant cells as far as we know according to our research. Based on this limited experience, lung carcinoma with OLGCs may represent a distinct clinicopathological entity with a more favorable prognosis. Careful microscopic examination and immunohistochemistry may be helpful in the differential diagnosis.
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