Microscopic description:

On light microscopic examination, the tumor was composed of large cuboidal to columnar cells forming cords and acinar structures. There was intracytoplasmic and extracellular mucin. The tumor morphology was similar to that seen on the right upper lobe of lung biopsy.

On immunohistochemistry the tumor cells were positive for CK7 and GATA-3 and were negative for CK-20, TTF-1, and Napsin A.

Discussion:

Mucinous adenocarcinoma is rather uncommon representing 10-15% of primary lung adenocarcinomas. The 2015 World Health Organization classification distinguishes invasive mucinous adenocarcinoma and colloid adenocarcinoma. 1 2 Their genetic profile is characterized by high frequency of KRAS mutations (up to 70%) with G12C KRAS mutation being most common. 3

While mucinous lung adenocarcinomas typically express CK7, in contrast to non-mucinous counterparts, they tend to show no expression of TTF1 and Napsin A. In up to 20%, mucinous adenocarcinomas can also express CK20.

GATA3 is an important transcription factor that is useful in the differentiation of breast epithelium, urothelia, and subsets of T lymphocytes. 4 5 It has been suggested to be useful in the evaluation of primary and metastatic carcinomas of mammary or urothelial origin. 6 In epithelial neoplasms, GATA3 was expressed in more than 90% of primary and metastatic ductal and lobular breast carcinomas, urothelial carcinomas, cutaneous basal cell carcinomas, and trophoblastic and endodermal sinus tumors. 7 Lung adenocarcinoma showing expression of GATA3 has been documented in the literature in approximately 12% of cases. Similarly, the frequency of expression of GATA 3 in adenocarcinomas of stomach, colon, endometrium, ovary, and prostate was <10%.


Conclusion:

The current case represents an uncommon presentation of invasive mucinous lung adenocarcinoma with metastasis to the trunk. GATA3 is a useful site specific marker in the characterization of mammary, urothelial, renal, and germ cell tumors; however, its expression in mucinous lung adenocarcinomas should be interpreted with caution.

References:

Galateau-Salle F, Churg A, Roggli V, Travis WD, World Health Organization Committee for Tumors of the Pleura. The 2015 World Health Organization Classification of Tumors of the Pleura: Advances since the 2004 Classification. J Thorac Oncol Off Publ Int Assoc Study Lung Cancer. 2016;11(2):142-154. doi:10.1016/j.jtho.2015.11.005

Wakejima R, Inamura K, Ninomiya H, et al. Mucinous lung adenocarcinoma, particularly referring to EGFR-mutated mucinous adenocarcinoma. Pathol Int. 2020;70(2):72-83. doi:10.1111/pin.12879

Ichinokawa H, Ishii G, Nagai K, et al. Distinct clinicopathologic characteristics of lung mucinous adenocarcinoma with KRAS mutation. Hum Pathol. 2013;44(12):2636-2642. doi:10.1016/j.humpath.2013.05.026

Lew M, Pang JC, Jing X, Fields KL, Roh MH. Young investigator challenge: The utility of GATA3 immunohistochemistry in the evaluation of metastatic breast carcinomas in malignant effusions. Cancer Cytopathol. 2015;123(10):576-581. doi:10.1002/cncy.21574

Sangoi AR, Shrestha B, Yang G, Mego O, Beck AH. The Novel Marker GATA3 is Significantly More Sensitive Than Traditional Markers Mammaglobin and GCDFP15 for Identifying Breast Cancer in Surgical and Cytology Specimens of Metastatic and Matched Primary Tumors. Appl Immunohistochem Mol Morphol AIMM. 2016;24(4):229-237. doi:10.1097/PAI.0000000000000186

Asch-Kendrick R, Cimino-Mathews A. The role of GATA3 in breast carcinomas: a review. Hum Pathol. 2016;48:37-47. doi:10.1016/j.humpath.2015.09.035

Mertens RB, de Peralta-Venturina MN, Balzer BL, Frishberg DP. GATA3 Expression in Normal Skin and in Benign and Malignant Epidermal and Cutaneous Adnexal Neoplasms. Am J Dermatopathol. 2015;37(12):885-891. doi:10.1097/DAD.0000000000000306

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