A PAX-8-Positive Female Urethral Adenocarcinoma, Intestinal-Type: A Case Report with Diagnostic Challenges and a Review of the Literature

Table 1

Demographic and immunohistochemical profiles for primary female urethral adenocarcinomas, columnar/mucinous subtype reported in the literature.

Author, year (reference)	Age (years)	Location	IHC	Number of cases ()
Meis et al., 1987 [9]	Mean, 63	U, PU, B, and V	MC+, PAS+	13
Hanai and Lin 1990^~ [11]	52	U	EMA+, CEA+, AFP+	1
Dodson et al., 1995 [6]	Unspecified	U	One case PAS+	11
Kato et al., 1998 [12]	71	U and V	CEA+, CA 19-9+, PSA-	1
Murphy et al., 1999 [4]	Unspecified	U	mAbDasl+, PSA-	9
Chan et al., 2000 [13]	72	U	CK7+, CK20+, PSA-	1
Kato et al., 2005 [14]	Mean, 66	U and PU	CEA+	5
Kuroda et al., 2006 [15]	77	U, PU, B, and V	CK7+, CA 19-9+, PSA+, CEA+, CA125+, ER-, PAP-, CK20-, PR-	1
Wang et al., 2012 [2]	44 & 52	U, B, and V	Unspecified	2
Hale et al., 2013` [16]	61	U and B	Immunoprofile in detail below`	1
Siosaki et al., 2013 [17]	62	U, B, and V	Unspecified	1
Satyanarayan et al., 2015 [5]	60	U	CK20+, CDX2+, CK7-	1
Harari et al., 2016 [10]	67	U	CDX2+ (80%), focally CK20+ (80%), focally CK7+ (80%), P63-, GATA3-, ER-, PAX-8-, β-catenin-	5
Muto et al., 2017`` [7]	69	U	PSAP+, AMACR+, CXD2+, CEA+, MUC2+, CK20+, NKX3.1-, PSA-, ER-, PAX-8-, GATA3-, CK7-, p40-, p63-	1
Gangadhar et al., 2018 [3]	60	U, PU, and V	PAS+	1
Tregnago and Epstein, 2018 [18]	63	PU	CK7+, ER+, focally CDX2+, HMWCK+, NKX3.1-, PSA-, P501S-, AMACR-, p63-, WT1-, PAX-8-, SATB2-, CK20-	1
Qin et al., 2019 [19]	63	U and B	CEA+, CK7+, CK20+, EMA+, p53+	1
Present case	64	U, B, and V	CK7+, CK20+, CDX2+, b-catenin+, CEA+, SATB2+, PAX-8+, TTF-1/Napsin-, p16-, ER-, vimentin-, GATA3-	1

U: urethra; PU: paraurethra; B: bladder; V: vagina; IHC: immunohistochemistry; MC: mucicarmine; PAS: periodic acid–Schiff; EMA: epithelial membrane antigen; CEA: carcinoembryonic antigen; AFP: alpha-fetoprotein; CA 19-9: cancer antigen 19-9; PSA: prostate-specific antigen; CK7: cytokeratin 7; CA125: cancer antigen 125; ER: estrogen receptor; PAP: prostatic acid phosphatase; CK20: cytokeratin 20; PR: progesterone receptor; CDX2: caudal-type homeobox 2; GATA3: GATA binding protein 3; PAX-8: paired box 8; HMWCK: high molecular weight cytokeratin; NKX3-1: NK3 homeobox 1; AMACR: alpha-methylacyl-CoA racemase; WT1: Wilms’ tumor 1; SAT-B2: special AT-rich sequence-binding protein 2. ^~Hanai and Lin report a case with three histologic patterns and partial AFP positivity: intestinal-type cells positive for EMA and CEA, EMA-negative and AFP-positive columnar vacuolated cells, and mainly EMA-positive clear cells. Dodson et al. report 11 cases of columnar/mucinous tumors that resembled either endometrial or colonic adenocarcinoma with the exception of one case that resembled prostatic adenocarcinoma. This one case was strongly positive for PSA, and the remaining columnar/mucinous adenocarcinomas were negative for PSA. One of the five cases had concurrent focal PSA positivity and two of the five cases had chromogranin A positivity. Kuroda et al. report a case with three histologic patterns including columnar/mucinous adenocarcinoma, clear cell adenocarcinoma, and papillary/micropapillary carcinoma without evidence of a cribriform pattern; all three histologic patterns were positive for CK7 and CA 19-9 and focally weak for PSA. Specifically, the columnar/mucinous adenocarcinoma component was also positive for CEA and CA 125. `Hale et al report a case with immunophenotype: PIN-4 (p63, 34βe12, and AMACR) positivity for p63 and 34βe12 in area of squamous metaplasia and a periurethral glandular remnant and PIN-4 negative in area of glandular metaplasia. An area of residual Skene’s gland tissue showed strong nuclear reactivity for p63. The metaplastic glandular cells lacked p63 staining. Nuclear Ki-67 reactivity in areas of squamous metaplasia showed 10% reactivity and in glandular areas was 5%. ``Muto et al. reviewed Skene’s gland adenocarcinoma, and their literature review revealed six cases of female urethral adenocarcinomas with evidence of a Skene’s gland origin; they also reported one original case (shown in the table).