Japanese Journal of Clinical Oncology

Figure 4 Adenoid basal carcinoma. (a) Keratin 17 expression is present in basaloid cells. (b) Keratin 18 expression is evident in cells surrounding true lumina [each 200×; (a) keratin 17 stain, (b) keratin 18 stain].

Macroscopically, a small polypoid tumor was identified at the uterine corpus (arrowhead), whereas the cervix appeared normal (Fig. 1). Histologically, the tumor at the corpus was a well differentiated endometrial adenocarcinoma in which the depth of invasion was limited to within the endometrium, and this was considered to be stage Ia according to the FIGO staging system.

Histological examinations of specimens from the surface epithelium of the uterine cervix showed carcinoma in situ (CIS) with glandular involvement (Fig. 2). Deep in the stroma beneath, small round-to-oval cancer cell nests, sometimes budding from the basal layer of the CIS, resembling those of basal cell carcinoma or basosquamous cell carcinoma of the skin, were evident; peripheral cell palisading was also found (Fig. 3). The tumor cells were small and uniform, with dark oval nuclei without conspicuous nucleoli and scanty cytoplasm. Mitotic activity was low. The central portions of the tumor cell nests formed cystic spaces filled with necrotic debris or eosinophilic material or occasionally showed squamous differentiation. Among the majority of PAS-negative cystic spaces forming false lumina, columnar cells surrounding PAS-positive secretory material forming true lumina were rarely seen (Fig. 3). No stromal reaction was evident. Neither lymphatic nor vascular invasion was identified and no metastasis was seen in sections taken from 18 excised lymph nodes. The cervical lesion was diagnosed as adenoid basal carcinoma and was at stage Ib.

Immunohistochemistry was performed using a labeled streptavidin-biotin staining kit (Dako, Carpinteria, CA, USA) according to the manufacturer's instructions. The polyclonal antisera and monoclonal antibodies used and their sources are listed in Table 1. For demonstration of keratins, estrogen receptor (ER), progesterone receptor (PgR), proliferating cell nuclear antigen (PCNA) and p53, antigen retrieval by microwave oven heating was essential (10). For negative controls, serial sections were incubated with non-immune serum at a comparable dilution. In addition, the ubiquity of the normal epithelium of the ecto- and endocervix served as a built-in positive control for keratin immunohistochemistry.

In this adenoid basal carcinoma, although mitoses were rare, PCNA labeled the majority of tumor cell nuclei, while stromal cells were almost always negative. In contrast, the stromal cells were consistently positive for ER and PgR, while the tumor cells were invariably negative. All tumor cells including the peripheral palisading cells were negative for S-100 protein and actin, suggesting no myoepithelial differentiation. The palisading basaloid cells at the periphery expressed keratins 7, 8, 14, 17 (Fig. 4), 18 and 19 and the foci of squamous differentiation expressed keratins 10 and 13. The cells surrounding true lumina were positive for keratins 7, 8, 18 (Fig. 4) and 19 and CEA. p53 staining of tumor cell nuclei was very rarely seen and CA125 staining was completely negative.

Table 1. Antisera and antibodies used in this study

Antigen	Antiserum/antibodies	Clone	Source
PCNA	Monoclonal	PC10	Novocastra, Newcastle upon Tyne, UK
ER	Monoclonal	1D5	Immunotech, Marseille, France
PgR	Monoclonal	10A9	Immunotech
S-100 protein	Polyclonal	-	Dako, Carpinteria, CA, USA
[alpha]-Smooth muscle actin	Monoclonal	HHF-35	Enzo, New York, NY, USA
Keratin 7	Monoclonal	RPN1162	Amersham, Buckinghamshire, UK
Keratin 8	Monoclonal	35[beta]H11	Enzo
Keratin 10	Monoclonal	DEK-10	Dako
Keratin 13	Monoclonal	KS-1A3	BioMakor, Rehovot, Israel
Keratin 14	Monoclonal	LL002	Novocastra
Keratin 17	Monoclonal	E-3	Bioprobe, Amstelveen, Netherlands
Keratin 18	Monoclonal	DC10	Dako
Keratin 19	Monoclonal	CK4.62	ICN Immunobiologicals, Lisle, IL, USA
CEA	Polyclonal	-	Dako
p53	Monoclonal	BP53-12	Bioprobe
CA125	Monoclonal	OC125	Lipshaw, Detroit, MI, USA

PCNA, proliferating cell nuclear antigen; ER, estrogen receptor; PgR, progesterone receptor; CEA, carcinoembryonic antigen; CA125, carbohydrate antigen 125.

Table 2 Clinical characteristics of 34 cases of adenoid basal carcinoma of the uterine cervix

Characteristic
Age	36-80 (mean 63) yr
Symptom	23/34:	asymptomatic
	8/34:	genital bleeding
	2/34:	cervical prolapse
	1/34:	abdominal mass
Gross appearance	20/29:	normal
	7/29:	erosion
	1/29:	polypoid
Associated lesion	25/28:	CIN
	1/28:	endometrial carcinoma + CIN
	2/28:	none
Prognosis	20/27:	alive (2-13 years)
	4/27:	died of other causes
	1/27:	died of uncertain cause
	1/27:	died of tumor with metastases
	1/27:	lost

CIN, cervical intraepithelial neoplasia.

Discussion

Adenoid basal carcinoma of the uterine cervix is an uncommon lesion for which the cell origin is still controversial. In the human female genital tract, the expression of various keratin polypeptides in normal and pathological specimens has been examined (11-13). Ectocervical squamous epithelium expressed keratins 14 and 19 in basal cells and keratins 10 and 13 in suprabasal cells. Endocervical columnar cells expressed keratins 7, 8, 18 and 19 and subcolumnar reserve cells expressed keratins which were found in endocervical columnar cells and also keratins 14 and 17. Tumors often express the keratins present in the original tissues and therefore these keratins can be used as tumor markers (14). In the present case, the basaloid cells expressed keratins 14, 17 and 19. In particular, the expression of keratin 17 resembled that of reserve cells of the cervical epithelium. In addition, the expression of keratins 10 and 13 in foci of squamous differentiation and of keratins 7, 8, 18 and 19 in cells surrounding a few lumina suggests that adenoid basal carcinoma shows distinct squamous and glandular differentiation.

The 34 cases of adenoid basal cell carcinoma (including the present case) reported previously in the English literature (1-3,5-9) are summarized in Table 2. Clinically, these adenoid basal carcinomas occurred almost exclusively in post-menopausal women, with a mean age of 63 years (36-80 years). The patients were usually asymptomatic (68%) and had come to medical attention after an abnormal cervical smear result. Symptoms, if present, included genital bleeding, cervical prolapse and abdominal mass. Grossly, most of the cervixes appeared normal (69%) and usually no gross mass was present. In most of the reported cases, adenoid basal carcinoma was associated with cervical intraepithelial neoplasia (CIN) (89%). In the present case, adenoid basal carcinoma was associated with CIN and endometrial adenocarcinoma and a review of the English literature failed to find a similar case. Generally, the clinical outcome is favorable, but distant metastasis was reported in one case.

Histologically, adenoid basal carcinoma is frequently confused with adenoid cystic carcinoma, which is also a rare neoplasm arising in the uterine cervix (2-4). The distinction between adenoid basal cell carcinoma and adenoid cystic carcinoma is summarized in Table 3. Grossly, adenoid cystic carcinoma frequently forms an irregular polypoid mass, whereas adenoid basal carcinoma usually does not form a gross mass. Histologically, adenoid basal carcinoma is characterized by less pleomorphic nuclei and less mitotic activity (2-5). Although mitosis was rare, a considerable amount of PCNA labeling, indicative of a high cell turnover, was seen in the present case. Formation of true lumina with microvilli is characteristic of adenoid cystic carcinoma (15). However, in the present case, true lumina were seen and these were surrounded by cells exhibiting a glandular phenotype, as demonstrated by keratin expression. Both adenoid basal carcinoma and adenoid cystic carcinoma show squamous differentiation within the cancer cell nests. Therefore, the existence of true lumina or squamous differentiation cannot be used to differentiate these two neoplasms. In adenoid cystic carcinoma, necrosis is common (4,16) and hyalinization is seen in the stroma (3,15-18), whereas adenoid basal carcinoma does not show such changes. Lymphatic invasion is seen in adenoid cystic carcinoma (15,17-19) but not in adenoid basal carcinoma. CIN is associated in both cancers, but more frequently in adenoid basal carcinoma (3).

Table 3 . Morphological distinction between adenoid basal carcinoma and adenoid cystic carcinoma of the uterine cervix

Morphology	Adenoid basal car.	Adenoid cystic car.
Cellular pleomorphism	Less	Common
Mitosis	Rare	Common
Lumen	False/true	False/true
Squamous nest	Present	Present
Necrosis	None	Common
Stromal reaction	None	Hyalinization
Lymphatic invasion	None	Present
CIN	Frequent	Rare
Metastasis	Very rare	Frequent
Prognosis	Favorable	Poor
Treatment	Radical surgery	Stage I*: radical surgery
		[ge]Stage II*: radical surgery and radiation

CIN, cervical intraepithelial neoplasia, car., carcinoma.*Stage according to the FIGO staging system.

The differential diagnosis of these two cancers is essential because the clinical outcome is markedly different (Table 3). Adenoid cystic carcinoma behaves aggressively, i.e. lymphatic invasion is common and local recurrence or metastatic spread is frequent, and about half of the reported patients died of the tumor or had local recurrence along with distant metastasis to the lungs, liver, bone or other sites (2,3,16-18). Since the prognosis of adenoid basal carcinoma is favorable, radical surgery is recommended. However, if the tumor is associated with adenocarcinoma or squamous cell carcinoma, the treatment will depend on the stage of these carcinomas (2). Since we found no hormone receptors (ER, PgR) in the present adenoid basal carcinoma, hormone therapy was not a treatment choice.

In conclusion, the reserve cells of the cervical epithelium and the basaloid cells of adenoid basal cell carcinoma are positive for keratins 14, 17 and 19, which share a similar keratin phenotype; however, glandular and squamous differentiation is also present. The tumor cells do not contain ER or PgR.

Acknowledgements

The authors thank Ms M. Fukuchi for typing the manuscript and Ms T. Akamatsu for technical assistance.

References

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Received March 27, 1997; accepted June 16, 1997
For reprints and all correspondence: Hideto Senzaki, Department of Pathology, Kansai Medical University, Fumizono-cho, Moriguchi-shi, Osaka 570, Japan
Abbreviations: CA125, carbohydrate antigen; CEA, carcinoembryonic antigen; FIGO, Federation Internationale de Gynecologie et d'Obstetrique; CIS, carcinoma in situ; ER, estrogen receptor; PgR, progesterone receptor; PCNA, proliferating cell nuclear antigen; CIN, cervical intraepithelial neoplasia

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Last modification: 19 May 1998
Copyright© Japanese Journal of Clinical Oncology, 1998.
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