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  Table of Contents    
Year : 2011  |  Volume : 54  |  Issue : 4  |  Page : 858-860
CDX2 positivity in metastatic endometrial carcinoma to the lung: A diagnostic pitfall

1 Department of Pathology, Tata Memorial Hospital, Dr. E Borges Road, Parel, Mumbai, India
2 Department of Medical Oncology, Tata Memorial Hospital, Dr. E Borges Road, Parel, Mumbai, India
3 Department of Thoracic Services, Tata Memorial Hospital, Dr. E Borges Road, Parel, Mumbai, India
4 Department of Surgery and Urological Oncology Surgery, Tata Memorial Hospital, Dr. E Borges Road, Parel, Mumbai, India

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Date of Web Publication6-Jan-2012

How to cite this article:
Deodhar KK, Gupta S, Karimundackal G, Tongaonkar H B. CDX2 positivity in metastatic endometrial carcinoma to the lung: A diagnostic pitfall. Indian J Pathol Microbiol 2011;54:858-60

How to cite this URL:
Deodhar KK, Gupta S, Karimundackal G, Tongaonkar H B. CDX2 positivity in metastatic endometrial carcinoma to the lung: A diagnostic pitfall. Indian J Pathol Microbiol [serial online] 2011 [cited 2022 May 29];54:858-60. Available from: https://www.ijpmonline.org/text.asp?2011/54/4/858/91535


CDX2 is a homeobox gene that plays a critical role in the development of the intestines. It has now firmly established itself as a marker of intestinal carcinoma when dealing with a clinical situation of metastatic adenocarcinoma of unknown origin. We, herein, report a case with a unique clinical history where CDX2 positivity is seen in metastatic endometrial adenocarcinoma to the lung, thus drawing our attention to a diagnostic pitfall.

A 59 yearold lady, diagnosed case of FIGO grade I endometrial adenocarcinoma, underwent left nephrectomy for metastasis, after nearly 4 years and was then referred to our hospital. About 2 years prior to nephrectomy, she had had pelvic recurrence for which radiotherapy was given. Positron emission tomography (PET) scan showed active disease in left lower lung and metastasis in right lung. She took five cycles of chemotherapy (Paclitaxel, Carboplatin) and showed good clinical and radiological response. After 1.5 years of follow-up, the lung tumor showed exaggeration and she took further four cycles of chemotherapy (Gemcitabine, Carboplatin). Subsequent bronchoscopic biopsy was taken and is currently described. On histology, it showed endometrioid adenocarcinoma with squamous differentiation [Figure 1]a-c. On IHC, the tumor cells were positive for CK7, ER [[Figure 2]a and c respectively] and were negative for CK20 [Figure 2]b, TTF1, CD 10 and WT1. Staining for β-catenin was equivocal. Focal positive staining for CDX2 was also seen [Figure 2]d. However, despite this finding, based on morphology, CK20 negativity and CK 7 positive staining, a diagnosis of metastatic endometrioid adenocarcinoma to the lung was made. She has been prescribed further chemotherapy.
Figure 1a: Bronchial biopsy with normal bronchial epithelium at one end (H and E, ×40)
Figure 1b: Tumor (endometrioid adenocarcinoma) with squamous differentiation (H and E, ×100)
Figure 1c: Tumor (endometrioid adenocarcinoma) with squamous differentiation (H and E, ×200)

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Figure 2a: Immunopositivity for CK 7 (IHC, ×100)
Figure 2b: Immunonegativity for CK 20 (IHC, ×100)
Figure 2c: Immunopositivity for ER (IHC, ×100)
Figure 2d: Immunopositivity for CDX2 (IHC, ×100)

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CDX2 is expressed, generally diffusely, in 70-85% of colorectal adenocarcinomas, and this expression is retained in metastatic foci. Its expression declines in poorly differentiated carcinoma (50%) and medullary carcinoma (20%). [1] CDX2 expression is also seen in tumors of gastroesophageal junction (50%), stomach (55-70%), ampulla (65-80%) and small intestine (60%); [2] as well as 5-30% pancreatic adenocarcinomas, cholangiocarcinomas and gall bladder carcinoma. [2] In nongastrointestinal cancers, it is seen in urachal, pulmonary mucinous and ovarian mucinous adenocarcinoma. [3]

Our interest in reviewing CDX2 staining in tumors stems from positive finding in this metastatic endometrioid adenocarcinoma. It is described, although uncommonly, and that to, in tissue microarray (TMA) studies. Delott et al. describe 5.9% positivity in endometrioid adenocarcinoma of the endometrium when they studied TMA bases 629 tumors from various sites. [2] Moskaluk et al. [4] also describe extensive nuclear CDX2 positivity in 1 out of 23 endometrioid adenocarcinoma cases of the endometrium (4.3%). Incidentally, normal proliferative and secretary endometrium showed CDX2 positivity. In a comprehensive study, Wani et al. [5] showed CDX2 positivity in 43.6% endometrioid adenocarcinomas and have observed that positivity is significantly higher when squamous differentiation is prominent, which was seen in our case. β-catenin expression also parallels in these tumors and it is possible that CDX2 expression is dependent on β-catenin accumulation in the nuclei. [5] Similarly, Hougton et al. observed CDX2 positivity in squamous morules postulating that these areas represent early squamous differentiation. [6] CDX2 positivity in a metastatic endometrioid adenocarcinoma has not been described.

The current case is informative in that it shows a diagnostic pitfall. In a small sample when squamous differentiation is not apparent, CDX2 positivity should not be solely relied upon to diagnose intestinal malignancy. Background history, morphology, coupled with CK7 positivity and negative staining for CK20 lead us in this case to the correct diagnosis. This finding is also relevant in considering differential diagnosis of a lung tumor mass.

   References Top

1.Winn B, Tavares R, Fanion J, Noble L, Gao J, Sabo E, et al. Differentiating the undifferentiated: Immunohistochemical profile of medullary carcinoma of the colon with an emphasis on intestinal differentiation. Hum Pathol 2009;40:398404.  Back to cited text no. 1
2.De Lott LB, Morrison C, Suster S, Cohn DE, Frankel W. CDX2 is a useful marker of intestinal-type differentiation. A tissue microarray based study of 629 tumors from various sites. Arch Pathol Lab Med 2005;129:11005.  Back to cited text no. 2
3.Rossi G, Murer B, Cavazza A, Losi L, Natali P, Marchioni A, et al. Primary mucinous (so called colloid)) carcinomas of the lung: A clinicopathologic and immunohistochemical study with special reference to CDX2 homeobox gene and MUC2 expression. Am J Surg Pathol 2004;28:44252.  Back to cited text no. 3
4.Moskaluk CA, Zhang H, Powell SM, Cerilli LA, Hampton GM, Frierson HF Jr. CDX2 protein expression in normal and malignant human tissues: An immunohistochemical survey using tissue microarray. Mod Pathol 2003;16:913-9.  Back to cited text no. 4
5.Wani Y, Notohara K, Saegusa M, Tsukayama C. Abberant CDx2 expression in endometrial lesions with squamous differentiation: Important role of Cdx2 in squamous morula formation. Hum Pathol 2008;9:1072-9.  Back to cited text no. 5
6.Houghton O, Connolly LE, McCluggage WG. Morules in endometrioid proliferations of the uterus and ovary consistently express the intestinal transcription factor CDX2. Histopathology 2008,53:156-65.  Back to cited text no. 6

Correspondence Address:
Kedar K Deodhar
Department of Pathology, Tata Memorial Hospital, Dr. E Borges Road, Parel, Mumbai - 400 012
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.91535

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This article has been cited by
1 Aberrant CDX2 expression and metastatic endometrial adenocarcinoma to the lung
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Indian Journal of Pathology and Microbiology. 2011; 54(4): 860-861


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