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Mucinous goblet cell carcinoma of lung

Definition

A primary tumour of lung, in which tumour cells float in large pools of mucin or focally line alveolar walls. Goblet cell mucinous carcinoma needs to be distinguished from primary signet ring cell carcinoma and mucinous bronchoalveolar carcinoma.

Epidemiology

Mucinous carcinoma of lung is rare, accounting for 0.25% of lung tumours.

Radiology

All cases of mucinous carcinoma of lung were peripheral solitary masses2. This contrasts with the ill-defined mass, lobar consolidation or ground glass appearance seen with mucinous bronchoalveolar carcinoma2.

Macroscopic appearances

All tumours appeared well circumscribed, sometimes with a central pseudocystic space. In contrast, the mucinous bronchoalveolar carcinomas were ill-defined and did not distort the lung architecture.

Histopathology

Classic goblet-cell mucinous adenocarcinomas were relatively paucicellular, being composed of large pools of mucin that disrupted the alveolar architecture. The sparse tumour cells do not line the alveolar walls continuously.

Signet ring cell carcinomas show similar pools of mucin, in which cells with signet ring cell morphology float freely. Mitoses are more common.

In contrast, the mucinous bronchoalveolar carcinomas were cellular, with lepidic growth completely lining intact alveolar walls. Typically, the tumour formed multiple micronodules, each of which stopped abruptly, separated by normal lung. The tumour cells sometimes formed papillary projections. Mucin lakes were not a prominent feature.

Immunohistochemistry

TTF-1 positivity in goblet cell mucinous carcinoma is not diffuse, being seen in 15-30% of nuclei in positive tumours2. Nuclear positivity for TTF-1 and CDX-2 are mutually exclusive2. A second paper confirms that staining in mucinous tumours is less intense than in other pulmonary adenocarcinomas3.

In summary (with mucinous and non-mucinous bronchoalveolar carcinoma and signet ring cell carcinoma of lung, plus mucinous adenocarcinomas of stomach and colon, for comparison):

Positivity of adenocarcinomas for CDX-2 and CK20, albeit with retention of CK7, at sites outside the gastrointestinal tract, may be a manifestation of the acquisition of an intestinal phenotype.

Differential diagnosis

• Mucinous cystadenoma of lung.

• Mucinous bronchoalveolar carcinoma of lung: a multicentric tumour with a lepidic growth pattern. It is negative for CDX-2 and MUC2. It has a relatively poor prognosis.

• Signet ring cell mucinous carcinoma of lung: an aggressive tumour.

• Metastatic mucinous carcinoma.

Prognosis

Goblet cell mucinous carcinoma of lung is a low-grade malignancy.

References

1 Merchant, S. H., Amin, M. B., Tamboli, P., Ro, J., Ordonez, N. G., Ayala, A. G., Czerniak, B. A., Ro, J. Y. Primary signet-ring cell carcinoma of lung: immunohistochemical study and comparison with non-pulmonary signet-ring cell carcinomas. Am J Surg Pathol 2001;25:1515-1519

2 Rossi, G., B. Murer, et al. (2004). "Primary mucinous (so-called colloid) carcinomas of the lung: a clinicopathologic and immunohistochemical study with special reference to CDX-2 homeobox gene and MUC2 expression." Am J Surg Pathol 28(4): 442-52.

3 Stenhouse, G., N. Fyfe, et al. (2004). "Thyroid transcription factor 1 in pulmonary adenocarcinoma." J Clin Pathol 57(4): 383-7. (with clarification from author)

4 Yatabe, Y., T. Koga, et al. (2004). "CK20 expression, CDX2 expression, K-ras mutation, and goblet cell morphology in a subset of lung adenocarcinomas." J Pathol 203(2): 645-52.

5 Goldstein, N. S. and M. Thomas (2001). "Mucinous and nonmucinous bronchioloalveolar adenocarcinomas have distinct staining patterns with thyroid transcription factor and cytokeratin 20 antibodies." Am J Clin Pathol 116(3): 319-25.

6 Shah, R. N., S. Badve, et al. (2002). "Expression of cytokeratin 20 in mucinous bronchioloalveolar carcinoma." Hum Pathol 33(9): 915-20.

7 Simsir, A., X. J. Wei, et al. (2004). "Differential expression of cytokeratins 7 and 20 and thyroid transcription factor-1 in bronchioloalveolar carcinoma: an immunohistochemical study in fine-needle aspiration biopsy specimens." Am J Clin Pathol 121(3): 350-7.

8 Jerome Marson, V., J. Mazieres, et al. (2004). "Expression of TTF-1 and cytokeratins in primary and secondary epithelial lung tumours: correlation with histological type and grade." Histopathology 45(2): 125-34.

9 Lau SK, Desrochers MJ,Luthringer DJ Expression of thyroid transcription factor-1, cytokeratin 7, and cytokeratin 20 in bronchioloalveolar carcinomas: an immunohistochemical evaluation of 67 cases. Mod Pathol 2002; 15:538-42

10 Saad RS, Cho P, Silverman JF, et al. Usefulness of Cdx2 in separating mucinous bronchioloalveolar adenocarcinoma of the lung from metastatic mucinous colorectal adenocarcinoma. Am J Clin Pathol 2004; 122:421-7

11 Tsuta K, Ishii G, Nitadori J, et al. Comparison of the immunophenotypes of signet-ring cell carcinoma, solid adenocarcinoma with mucin production, and mucinous bronchioloalveolar carcinoma of the lung characterized by the presence of cytoplasmic mucin. J Pathol 2006; 209:78-87

This page last revised 20.12.2008.

©SMUHT/PW Bishop