JOURNAL OF PATHOLOGY, VOL.

167: 305-3 1 1 (1992)

‘PLEURAL’ AND PULMONARY CARCINOSARCOMAS FREDERICK G. MAYALL AND ALLEN R. GIBBS

Department of Histopathology, Llandough Hospital, Penarth, South Glamorgan CF6 I X X and Department of Pathology, University of Wales College of Medicine, Heath Park, Cardiz, South Glamorgan CF4 I X N , U.K. Received20 November I991 Accepted28 January 1992

SUMMARY The histological distinction between carcinosarcoma and mesothelioma has received little attention. The object of this study was to describe the histology and immunohistochemistry of two carcinosarcomas presenting as pleural tumours. These were compared with 12carcinosarcomas from sites within the lung, and with the established features of mesothelioma. Histologicallyand immunohistochernically,these ‘pleural’carcinosarcomas are similar to conventional pulmonary carcinosarcomas but accurate recognition is hindered by their gross appearance and biphasic histology which closely mimic mesothelioma. They may exhibit features such as neutral mucin, expression of carcinoembryonic antigen, squamous differentiation, and neuroendocrine differentiation which, when present, are evidence against mesothelioma. These tumours are rare and have passed unnoticed until now. KEY

wom-Carcinosarcoma,

mesothelioma, carcinoma, pleura, lung, immunohistochemistry, nickel.

INTRODUCTION In the WHO classification of lung tumours,’ a carcinosarcoma is a malignant tumour having an admixture of carcinoma and sarcoma. There are difficulties in the application of this definition due to uncertainty as to what constitutes ‘sarcoma’. Some would only accept unequivocal histological evidence of mesenchymal differentiation such as rhabdomyosarcomatous, chondrosarcomatous, or osteosarcomatous features,’ while others would be satisfied with a fibrosarcomatous spindle cell pattern. At the other end of the spectrum, tumours which appear to be primary sarcomas of the lung may show epithelial differentiation on immunohist~chemistry~ and are in fact carcinosarcomas with a histologically inconspicuous epithelial element. In recognition of the inherent problem in the diagnosis of this tumour, the WHO qualifies the definition with the phrase ‘Carcinosarcomas are Addressee for correspondence: Dr F. G. Mayall, Department of Histopathology, Llandough Hospital, Penarth, South Glamorgan CF6 IXX, U.K.

0022-341 7/92/07030547 $08.50 0 1992 by John Wiley & Sons, Ltd.

difficult to distinguish from spindle cell (squamous) carcinomas unless differentiation into specifictissues such as neoplastic bone, cartilage and striated muscle is seen’.’ However, this does not resolve the uncertainty in the classification of apparently biphasic tumours without any specific differentiation in their sarcomatous component, and there is probably a significant inter-observer variation in the classification of these tumours. The diagnosis is even more problematic in biopsy and cytology specimens4 because of the limited amount of material available for examination. From a prognostic point of view, the distinction between spindle cell carcinoma and carcinosarcoma is probably not very important as the biological behaviour of both appears to be similar.536 Our interest in these tumours has developed as a result of two cases that we have recently encountered in which there was a pleural tumour encasing the lung in a manner suggestive of mesothelioma. Little attention has been paid in the past to the histological distinction between carcinosarcoma and mesothelioma, but in cases such as these accurate diagnosis may be important because of the legal implications. The object of this study was to

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F. G. MAYALL AND A. R. GIBBS

describe the histology and immunohistochemistry of these two ‘pleural’ carcinosarcomas, comparing them with 12 pulmonary carcinosarcomas with a more conventional gross appearance, and with the established histological and immunohistochemical features of mesothelioma. We were particularly interested in verifying that these pleural tumours were carcinosarcomas and in identifying reliable distinctions between them and mesotheliomas.

METHOD All 14 cases of carcinosarcoma were obtained from surgical and post-mortem material examined in our department. For each, patient age, sex, occupation, smoking habits, therapy, and other clinical details were collected from clinical records. Details concerning the gross appearance of the tumours, their dimensions, and locations were collected from the original reports or from the formalin-fixed specimens when possible. A representative block of tumour was selected from each case and 5 pm sections werecut and dewaxed. These were stained with haematoxylin and eosin (H & E), alcian blue, and diastase periodic acid-Schiff (DPAS) and were examined by two pathologists. The differentiation of the epithelial component was typed according to its monophasic counterpart in the WHO classification’ and any specific form of mesenchymal differentiation, such as osteoid formation, was noted. Five pm sections for immunohistochemistry were cut from the same blocks as those for the conventional histology. These were immunostained with commercially available primary antibodies to broad spectrum cytokeratin (CK), SlOO (Diagnostic Products Corp., 31 Station Road, Witney, Oxon, U.K.), carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), vimentin, and desmin (Dako Ltd., 16ManorCourt, Hughenden Ave, High Wycombe, Bucks, U.K.) according to the manufacturer’s directions. Immunostaining was completed using an appropriate commercial peroxidaseconjugated avidin method (Dako Ltd.). Histology suggested neuroendocrine differentiation in the epithelial component of case 2. Sections from this tumour were immunostained for neuron-specific enolase (NSE), bombesin, and chromogranin using previously described method^.^ Suitable positive and negative control sections were processed with each batch of immunostains. Particular attention was

paid to the distribution of positive immunostaining between the epithelial and the stromal components of the tumours. RESULTS The results are presented in Tables I and 11. The first pleural tumour (case 1) was associated with a putative occupational history of asbestos exposure, but lung analysis by transmission electron microscopy and energy dispersive X-ray microanalysis’ gave an asbestos fibre count within the normal range. However, this analysis did demonstrate a very high level of nickel in the lung tissue which, it transpired, was acquired industrially. The second pleural tumour (case 2) was also associated with putative asbestos exposure but the transmission electron microscopic fibre count was normal. Asbestos fibre counts were not performed on the other cases as there was no reason to suspect exposure. Case 1 had a large, predominantly pleural tumour which encased the lung in a manner typical of mesothelioma (Fig. 1). Case 2 showed tumour involvement of the left upper lobe pleura, but this did not extend to the lower lobe. There was a good deal of focal variation in the thickness of the tumours, with compression and distortion of the underlying lung. It was not possible to identify a site of origin within the lung tissue for either tumour. On microscopy, both pleural tumours had a biphasic appearance. In case 1 , this consisted of a pleomorphic, mitotically active, spindle cell stromal component (including foci of osteoid) surrounding an acinar epithelial component (Figure 2) with focal squamous differentiation including keratin pearls, which were also seen in the epithelial component of the hilar node metastases (Fig. 3). There were small collections of neutral mucin within some of the acini but no acid mucin was demonstrated. On the basis of these findings, the epithelial component was classified as adenosquamous type. In case 2, the lobectomy specimen showed a sarcomatous tumour with an inconspicuous epithelial component. The stroma was highly cellular with a mixture of mitotically active ovoid and spindle cells (Fig. 4). At autopsy, the epithelial component was more obvious in the residual tumour. The variation between patterns was less focal than in case 1, and in some regions a monotonous arrangement of uniform small epithelial cells occupied whole low power fields (Fig. 4). Foci of necrosis

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‘PLEURAL’AND PULMONARY CARCINOSARCOMAS

Table I-Details

of presentation, treatment, and survival Smoking habit (cigarettes /day)

Case

Sex

Age (years)

Presenting symptoms

1

M

69

Dyspnoea and effusion

20

No treatment

2

F

59

Chest and arm pain

10

Left upper lobectomy, pleurectomy, and radiotherapy Right pneumonectomy Had coincident largyngeal carcinoma, carcinoma in situ Right lower lobectomy

3

M

45

Haemoptysis

15

4

M

61

Weight loss

15

5

M

58

Cough

6

M

72

7

M

8

Treatment

Notes Heavy industrial nickel exposure; asbestos fibre count normal Asbestos fibre count normal

Survival (months) Died