Cervical adenoid basal tumors comprised of adenoid basal

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Cervical adenoid basal tumors comprised of adenoid basalepithelioma associated with various types of invasivecarcinoma: Clinicopathologic features, humanpapillomavirus DNA detection, and P16 expression

Anil V. Parwani MD, PhDa, Ann E. Smith Sehdev MDa,1, Robert J. Kurman MDa,b,Brigitte M. Ronnett MDa,b,*

aDepartment of Pathology, The Johns Hopkins University School of Medicine and Hospital, Baltimore, MD 21231, USAbDepartment of Gynecology and Obstetrics, The Johns Hopkins University School of Medicine and Hospital,

Baltimore, MD 21231, USA

Received 28 June 2004; accepted 25 August 2004

0046-8177/$ – see front matter D 2005

doi:10.1016/j.humpath.2004.08.015

Abbreviations: HPV, human papillom

* Corresponding author. Department

E-mail address: [email protected] Currently at Department of Patholo

Keywords:Adenoid basal tumor;

Adenoid basal carcinoma;

Cervical carcinoma;

Human papillomavirus

DNA;

p16 immunohisto-

chemistry

Summary Adenoid basal tumors are uncommon cervical lesions that some pathologists consider

invasive carcinomas but others consider bepitheliomasQ due to their low-grade histological appearance

and rarely documented malignant behavior. We report the clinicopathologic features of 10 tumors

comprised of both typical low-grade adenoid basal tumors (epitheliomas) intimately associated with

invasive carcinomas having infiltrative growth, increased cytological atypia and mitotic activity, and

various types of differentiation, including adenoid basal/squamous, pure squamous, adenoid cystic, and

small cell neuroendocrine. Tumors were evaluated for the presence of human papillomavirus (HPV)

DNA and immunohistochemical p16 expression. The patients in the study group ranged in age from 45

to 81 years (mean, 65 years). Most of the patients presented with abnormal cervicovaginal smears. The

initial diagnosis was made on specimens obtained by cervical biopsy, laser electrocautery excision

procedure (LEEP), or cone biopsy in 8 patients. Two 2 patients were incidentally diagnosed in

hysterectomy specimens. All 10 patients had squamous intraepithelial lesions (9 high-grade, 1 low-

grade). In all cases diagnosed in LEEP or cone biopsy specimens, the invasive carcinoma component

was present in the excisional specimen and extended to the margins. Seven patients diagnosed on

excisional or biopsy specimens who underwent hysterectomy had residual tumor in the cervix, ranging

from microscopic foci to deeply invasive. No lymph node metastases were identified in 4 patients who

were staged. Seven patients with follow-up were alive without evidence of disease after follow-up

intervals of 8 to 84 months (mean, 45 months; median, 29 months). One patient with a component of

small cell carcinoma died of other causes without evidence of disease at 18 months. HPV 16 DNAwas

detected in both the adenoid basal epithelioma and invasive carcinoma components in 9 tumors by in

Human Pathology (2005) 36, 82–90

Elsevier Inc. All rights reserved.

avirus; LEEP, laser electrocautery excision procedure; PCR, polymerase chain reaction.

of Pathology, Johns Hopkins Hospital, Weinberg Bldg., Room 2242, 401 N. Broadway, Baltimore, MD 21231.

(B.M. Ronnett).

gy, Good Samaritan Hospital, Portland, OR.

Cervical adenoid basal tumors 83

situ hybridization, and HPV 33 was detected by polymerase chain reaction in 1 tumor. All tumors

expressed p16 diffusely. Adenoid basal tumors are high-risk HPV-related tumors that can be comprised

of both a low-grade adenoid basal tumor, which can be designated as epithelioma, and invasive

carcinomas of various types. The invasive component is usually evident in the excisional biopsy

specimen, allowing for recognition of a tumor that needs further management.

D 2005 Elsevier Inc. All rights reserved.

1. Introduction

Adenoid basal tumors of the cervix have been designated

as badenoid basal carcinomasQ since their initial recognition,even though malignant behavior has rarely been observed

[1-8]. They are unusual cervical tumors composed of nests of

uniform cells displaying basaloid, squamous, and glandular

differentiation. The tumors are usually associated with

squamous intraepithelial lesions, most often high-grade.

Most affected patients are asymptomatic postmenopausal

women who are diagnosed during follow-up of an abnormal

cervicovaginal smear. Pure, typical tumors appear to behave

in a benign fashion, leading the authors of one study to

recommend the term badenoid basal epitheliomaQ rather thanadenoid basal carcinoma [9]. Although the cases described in

that report were not associated with other types of invasive

carcinomas (except for 1 case of a microinvasive squamous

carcinoma), some other reports have described adenoid basal

tumors associated with invasive carcinomas and carcinosar-

comas [3,4,10-12]. In the present study we describe the

clinicopathologic features of a series of adenoid basal tumors

composed of a typical low-grade adenoid basal component

(bepitheliomaQ) intimately associated with invasive carcino-

mas displaying one or more types of differentiation. We

investigate the relationship between the adenoid basal

epitheliomas and invasive carcinomas by assessing for the

presence of HPV DNA and p16 expression in both tumor

components. We then present a proposal to subclassify these

tumors into adenoid basal epitheliomas and carcinomas.

2. Materials and methods

This study was approved by the Johns Hopkins Institu-

tional Review Board. The files of the Gynecologic Pathology

Consultation Service and Surgical Pathology Division, The

Johns Hopkins Hospital were searched for cases designated

as adenoid basal carcinoma, adenoid basal tumor, adenoid

basal and squamous carcinoma, or adenoid basal epithelioma

for the period 1984 to 2004. Of 14 potential cases of low-

grade adenoid basal tumor associated with additional types

of invasive carcinoma, 10 retrievable cases (9 consultation

cases and 1 routine case) were identified. Typical low-grade

adenoid basal tumors (n = 19) were excluded from the study.

2.1. Immunohistochemistry for p16

Formalin-fixed, paraffin-embedded tissue sections were

used. Immunoperoxidase labeling was done with an

automated BioTek-Tech Mate 1000 Staining System (Ven-

tana/Biotek Solutions, Tucson, AZ) at room temperature

with anti-p16(INK4a) (MTM Laboratories AG, Heidelberg,

Germany) at a dilution of 1:500.

2.2. Human papillomavirus DNA detection byin situ hybridization

Formalin-fixed, paraffin-embedded tissue sections were

used. Biotin-labeled HPV probe solutions (Dako, Carpin-

teria, CA) were applied to individual sections. These

included a wide spectrum probe (cocktail of HPV 6, 11,

16, 18, 31, 33, 45, and 51) and separate type-specific probes

for HPV 16 and HPV 18. Detection of hybridized probe was

done by tyramide-catalyzed signal amplification using the

Genpoint kit (Dako). Chromogenic detection was performed

with diaminobenzidine/H2O2. Controls included tissue

sections positive for HPV wide spectrum, the HeLa cell

line for HPV 18, and the SiHa cell line for HPV 16. Biotin-

labeled plasmid probes served as negative controls in each

case. Cases with a discrete punctate reaction product

specifically in tumor cell nuclei were interpreted as positive.

2.3. HPV DNA detection by polymerasechain reaction

To further analyze the tumors for the presence of HPV,

polymerase chain reaction (PCR) for HPV DNA was

performed on those specimens that were negative by in situ

hybridization. Tissue sections were deparaffinized with

xylene and resuspended and digested with buffer containing

proteinase K. Amplifications were performed for betaglobin

and for HPVs by the Roche line blot method [13]. This

method uses biotinylated pooled primers for HPV and for

betaglobin amplification. The amplified products are

screened against more than 35 HPV probes and betaglobin

probes immobilized on an extended filter strip. Specimens

that are negative for betaglobin and HPV are consid-

ered unsatisfactory.

3. Results

3.1. Clinicopathologic features

The clinicopathologic features of the 10 cases are

summarized in Table 1. The patients ranged in age from

45 to 81 years (mean, 65 years). Most of the patients

presented with abnormal cervicovaginal smears. The initial

A.V. Parwani et al.84

diagnosis was made on an excisional biopsy specimens

obtained by laser electrocautery excision procedure (LEEP)

or cone biopsy in 6 patients and in biopsy specimens in 2

patients. In 2 patients, the tumors were incidentally

diagnosed in hysterectomy specimens removed for pelvic

relaxation and uterine prolapse. The overlying cervical

squamous mucosa demonstrated a squamous intraepithelial

Table 1 Clinicopathologic Features of Cervical Adenoid Basal Tumo

Case Age Cervicovaginal

smear findings

Diagnostic

specimen

Invasiv

1 70 ASCUS, AGUS LEEP Adenoi

carcino

2 71 Abnormal* Cone biopsy Adenoi

carcino

3 79 HSIL Cone biopsy Adenoi

carcino

neuroe

4 81 Abnormal* Cone biopsy Squam

adenoid

5 61 HSIL Biopsy Adenoi

carcino

6 65 HSIL Cone biopsy Microi

carcino

7 45 HSIL Biopsy Adenoi

carcino

8 64 NA Hysterectomy Squam

9 49 HSIL LEEP Adenoi

carcino

10 65 NA Hysterectomy Adenoi

carcino

Tumor size, cm

(maximum dimension /

maximum depth)

Treatment

1 1.2 /0.3 Radical hysterectomy,

lymphadenectomy

2 0.6 /0.4 Total abdominal

hysterectomy, BSO;

Radiation therapy

3 At least 0.8 /0.5 Radiation therapy


BSO, lymphadenectomy

5 1.0 /0.8 Total vaginal

hysterectomy, RSO


lymphadenectomy

7 3.3 /1.4 Total abdominal

hysterectomy, BSO,

lymphadenectomy;

Radiation therapy

8 1.0 /0.6 Hysterectomy


BSO, lymphadenectomy

10 1.6 /0.8 Total vaginal hysterectomy

Abbreviations: ASCUS, atypical squamous cells of undetermined significance; AG

squamous intraepithelial lesion; LSIL, low-grade squamous intraepithelial lesion;

ND, not done; NA, not available; NED, no evidence of disease; DOC/NED, died

* Pap smear reported as abnormal, not further specified.

lesion in all cases (9 high-grade, 1 low-grade). Each tumor

was comprised of typical low-grade adenoid basal tumor

intimately associated with invasive carcinoma. The low-

grade adenoid basal tumor components were characterized

by discrete nests of tumor in which the surrounding stroma

lacked a desmoplastic reaction. The epithelial nests dis-

played varying combinations of basaloid, squamous, and

rs

e carcinoma type Intraepithelial lesion Margin status

on excision

d basal/squamous

ma

HSIL Positive

d basal/squamous

ma

HSIL Positive

d basal/squamous

ma and small cell

ndocrine carcinoma

HSIL Positive

ous carcinoma and

cystic carcinoma

LSIL Positive

d basal/squamous

ma

HSIL –

nvasive squamous

ma

HSIL Positive

d basal/squamous

ma

HSIL –

ous carcinoma HSIL –

d basal/squamous

ma

HSIL Positive

d basal/squamous

ma

HSIL Negative

Margin status on

hysterectomy

Lymph node status

(positive/total)

Follow-up

status, months

Negative Negative (0/26) NED, 27

Positive ND NED, 72

ND ND DOC/NED, 18

Positive, with

tumor in parametria

Negative (0/19) NED, 18

Negative ND NED, 29



Negative ND NED, 8

Negative Negative (0/41) Recent case

Negative ND Recent case

US, atypical glandular cells of undetermined significance; HSIL, high-grade

BSO, bilateral salpingo-oophorectomy; RSO, right salpingo-oophorectomy;

of other causes with no evidence of disease.

Fig. 1 Adenoid basal epithelioma (the associated invasive

carcinoma is not illustrated). The low-grade noninfiltrative compo-

nent is illustrated. Nests of tumor display basaloid, squamous, and

glandular differentiation. The stroma lacks a desmoplastic response.

Fig. 2 Adenoid basal epithelioma (the associated invasive

carcinoma is not illustrated). The low-grade noninfiltrative compo-

nent associated with invasive carcinoma is illustrated. Nests of

tumor display basaloid and glandular differentiation. The stroma

lacks a desmoplastic response.

Fig. 3 Invasive squamous carcinoma associated with adenoid

basal epithelioma. Low magnification illustrates small nests of

adenoid basal epithelioma (top) associated with larger nests of

invasive squamous carcinoma.


glandular differentiation with minimal atypia and mitotic

activity (Figs. 1 and 2). The low-grade adenoid basal tumor

was connected to the overlying squamous intraepithelial

lesion in 3 cases. In all tumors, the low-grade adenoid basal

tumor component merged with areas of invasive carcinoma

(Fig. 3). These areas of invasive carcinoma were distinct

from the low-grade adenoid basal tumor components in that

the carcinomatous components exhibited greater nuclear

atypia and increased mitotic activity compared with the

low-grade components and had infiltrative patterns. Thus

there was little or no stromal response to the low-grade

components, but in the carcinomatous components the

surrounding stroma exhibited a more spindled or myxoid

appearance, often with inflammatory cells, consistent with

stromal desmoplasia (Fig. 4). The invasive carcinomatous

components in the tumors exhibited varying degrees of

adenoid basal and squamous differentiation. Adenoid basal

differentiation was characterized by cells in the nests with

scanty cytoplasm, peripheral palisading, and focal gland

formation (Figs. 4 and 5), and squamous differentiation was

manifested by increased amounts of dense eosinophilic

cytoplasm in cells within the central portions of these nests

(Fig. 6). Thus some invasive components had pure adenoid

basal differentiation, some displayed combined adenoid

Fig. 4 Invasive adenoid basal carcinoma. This deeply invasive

tumor displays predominantly basaloid and focal glandular

differentiation. A focus of tumor is present within a lymphatic

space (upper right).

Fig. 5 Invasive adenoid basal/squamous carcinoma. Basaloid

differentiation in the carcinoma is characterized by cells with

scanty cytoplasm and peripheral palisading. The smaller nest of

tumor at the top displays glandular (badenoidQ) differentiation.

There is nuclear atypia, and numerous mitotic figures are evident.


basal and squamous differentiation, and some had pure

squamous differentiation (Figs. 3 to 6). A focus of

lymphatic invasion was identified in 1 case (Fig. 4). One

tumor also had a component of adenoid cystic carcinoma,

solid variant (Figs. 7 and 8). In another tumor, most of the

invasive component exhibited features of a high-grade

small cell neuroendocrine carcinoma, characterized by cells

with hyperchromatic nuclei, nuclear molding and stream-

ing, and minimal cytoplasm (Fig. 9). This component was

focally positive for cytokeratin and expressed neuroendo-

crine markers. In the 6 cases diagnosed on excisional

biopsy specimens, the invasive carcinoma extended to the

margins of those specimens (Fig. 7).

Most patients were treated with some form of hysterec-

tomy, often with bilateral salpingo-oophorectomy and

lymph node dissection. All those treated by surgery had

residual tumor in the cervix, ranging from just residual

adenoid basal tumor in the case with microinvasive

squamous carcinoma (in the excisional biopsy specimen)

to variable amounts of residual invasive carcinoma. The

amount of residual carcinoma ranged from microscopic foci

to deeply invasive tumor. For those cases in which

maximum dimensions could be obtained, the tumors ranged

in size from 0.4 to 3.3 cm in greatest dimension, with depth

of invasion ranging from 0.2 to 1.4 cm. Most cases had

negative margins on the hysterectomy specimens, and all

cases with lymph node dissections had no evidence of

lymph node metastases. However, 1 case had positive

margins with unknown lymph node status, and another case

had involvement of the parametria with a positive margin

but negative lymph nodes. Seven of 8 patients with

available follow-up were alive without evidence of disease

after follow-up intervals of 8 to 84 months (mean, 45

months; median, 29 months); 2 cases were recent, with very

limited follow-up. One patient with a component of small

cell carcinoma died of other causes, without evidence of

disease on imaging studies, at 18 months.

3.2. Immunohistochemical p16 expression and HPVdetection by in situ hybridization and PCR

All tumors exhibited diffuse expression of p16

(cytoplasmic, often with nuclear as well) in both the

adenoid basal epithelioma and invasive carcinoma com-

ponents (Fig. 10). HPV 16 DNA was detected in both the

adenoid basal epithelioma and invasive carcinoma com-

ponents in 9 tumors (Fig. 11). The positive reactions were

characterized by discrete punctate reactivity confined to

Fig. 6 Invasive adenoid basal/squamous carcinoma. Invasive

carcinoma exhibits mixed basaloid and squamous differentiation.

Basaloid differentiation is seen at the periphery of the nests, where

palisading is evident. The central portion of the nest contains cells

with more abundant dense eosinophilic cytoplasm, indicating

squamous differentiation. There is nuclear atypia, and an abnormal

mitotic figure is present.


tumor nuclei. In 1 tumor (case 9), HPV DNA was not

detected by in situ hybridization, but PCR demonstrated

the presence of HPV 33.

Fig. 7 Mixed adenoid cystic carcinoma and squamous carcino-

ma associated with adenoid basal epithelioma. Low magnification

illustrates solid nests of adenoid cystic carcinoma (lower portion)

extending to the margin of the excisional specimen. Adjacent

tumor (upper portion) consists of small nests of adenoid basal

epithelioma (upper right) and slightly larger nests of squamous

carcinoma (upper left).

4. Discussion

Adenoid basal tumors are uncommon tumors of the

cervix that have been designated as badenoid basal

carcinomasQ in most reports [1-8]. More recently, the

designation badenoid basal epitheliomaQ has been suggested

as a more appropriate term, because most reported cases

have been associated with benign behavior [9]. Of 39 cases

reported in 7 studies, only 1 patient died of tumor [8], but it

appears that the tumor in that fatal case had unusual

histological features and may have been a high-grade

invasive basaloid carcinoma rather than a typical adenoid

basal tumor [1,2,6,8,9,14,15]. In addition, several studies

have emphasized the need to distinguish adenoid basal

tumors from adenoid cystic carcinomas of the cervix

because the latter are associated with a distinctly unfavor-

able prognosis [3,6,8,16].

Based on the collective experience in the literature, with

specific reference to points made in the study suggesting the

term bepitheliomaQ and the cases in the current study, several

observations can be made. First, based on the previous

studies, it appears that pure, typical adenoid basal tumors

(without malignant cytological features and unassociated

with other forms of invasive carcinoma) lack many of the

features of a malignant neoplasm and virtually always behave

in a benign fashion, even when present deep within the

cervical stroma [9]. Second, based on the cases in our study

and other reports in the literature, some typical adenoid basal

tumors can be associated with an unequivocal invasive

carcinoma displaying the microscopic features of carcinoma,

including increased cytological atypia, mitotic activity with

abnormal mitotic figures, and deeply infiltrative growth of

these cytologically malignant components. In addition, the

invasive components can display patterns of differentiation

indicating specific subtypes of invasive carcinoma with

established malignant behavior, including squamous, ade-

noid cystic, and small cell neuroendocrine carcinomas.

Although no lymph node metastases or tumor-related

deaths were observed in our study, all of the tumors

contained a carcinomatous component displaying malignant

cytological features; in addition, many deeply invaded the

cervical stroma, and some extended to margins or involved

the parametrial soft tissue. Notable cytological atypia and

deeply infiltrative growth are pathological features associ-

Fig. 8 Adenoid cystic carcinoma. Higher magnification of the

tumor in Fig. 7 illustrates the typical appearance of the solid form

of adenoid cystic carcinoma.

Fig. 9 Small cell neuroendocrine carcinoma associated with

adenoid basal epithelioma. Small cell carcinoma component (lower

portion) is composed of undifferentiated cells with scanty

cytoplasm and hyperchromatic nuclei displaying nuclear molding

and streaming. Small nests of adenoid basal epithelioma (upper

portion) are seen adjacent to the carcinoma.


ated with carcinomas rather than benign tumors; hence, use

of the term bcarcinomaQ is appropriate for tumors exhibiting

these features despite the lack of documented malignant

behavior in the reported tumors.

We suggest the following approach to diagnosing the

spectrum of tumors exhibiting adenoid basal differentiation.

Pure low-grade adenoid basal tumors lacking appreciable

cytological atypia, mitotic activity, and an infiltrative pattern

in a desmoplastic stroma (ie, without evidence of invasive

carcinoma of adenoid basal/squamous, pure squamous,

adenoid cystic, or other type) that are confined to an

excisional specimen with clearly negative margins can be

designated as badenoid basal epitheliomas.QThis terminology

has been recommended by other investigators and is more

appropriate than the term badenoid basal hyperplasia,Qbecause it acknowledges that these lesions are neoplasms

that may be precursors of the associated invasive carcinomas

occasionally encountered [9,17]. Tumors composed of both

typical low-grade adenoid basal tumor (epithelioma) and an

invasive, cytologically malignant component exhibiting

adenoid basal/squamous, pure squamous, and/or adenoid

cystic differentiation can be diagnosed as invasive carcino-

mas based on their morphological features. Those with mixed

differentiation can be subclassified according to the patterns

of differentiation (such as mixed adenoid basal/squamous

carcinoma, or mixed squamous and adenoid cystic carcino-

ma). Many tumors with the features of carcinoma may well

behave in a benign fashion after complete excision based on

the experience in the literature and this study, but the

designation bcarcinomaQ is appropriate in view of their

morphological features. Thus most adenoid basal tumors

can be classified as either epithelioma or carcinoma when

either the entire lesion is available for evaluation or the

microscopic features of malignancy are present.

Tumors extending to the margins of an excisional

specimen but lacking cytological features of malignancy

and the histological features of typical invasive squamous,

adenoid basal, or adenoid cystic carcinoma pose some

difficulty, in that adequacy of treatment cannot be deter-

mined. Accordingly, in practice such tumors can be

designated as adenoid basal epithelioma with a comment

that the possibility of an invasive carcinomatous component

cannot be excluded due to incomplete evaluation in the

setting of a positive margin. In such cases another excisional

specimen or hysterectomy is required to exclude an invasive

component and assure adequate treatment.

Other investigators have demonstrated by both in situ

hybridization and PCR that cervical adenoid basal carcino-

mas, adenoid cystic carcinomas, and small cell carcinomas

contain HPV DNA (most often HPV 16) [4,5,7,18,19]. Our


study confirms these observations and demonstrates that

both the adenoid basal epithelioma and invasive carcinoma

components contain high-risk HPV. In addition, the finding

of high-risk HPV DNA in both components suggests that

the carcinomas arose from the adenoid basal epitheliomas

and lends further support to the concept that the epithelio-

mas are neoplastic precursor lesions [17]. Immunohisto-

chemical detection of p16 expression is associated with

high-risk HPV infection in cervical intraepithelial lesions

and invasive carcinomas and can serve as a surrogate

marker of high-risk HPV infection in the appropriate

pathological setting [20,21]. The diffuse expression of p16

in all tumors in our study, including 1 tumor in which HPV

DNA was not detected by in situ hybridization, indicates

that immunohistochemical expression of p16 can be used as

a surrogate marker of high-risk HPV infection in these

tumors when in situ hybridization reactions do not detect

HPV due to technical reasons or when in situ hybridization

and PCR techniques are not available in the laboratory. The

finding of various subtypes of high-risk HPV-related

invasive cervical carcinomas intimately associated with

adenoid basal epitheliomas in our cases lends support to

the concept that adenoid basal tumors are of putative reserve

Fig. 10 Mixed adenoid cystic carcinoma and squamous carci-

noma associated with adenoid basal epithelioma. Diffuse expres-

sion of p16 is evident in all components of the tumor illustrated

in Fig. 7.

Fig. 11 Mixed adenoid cystic carcinoma and squamous carci-

noma associated with adenoid basal epithelioma. Adenoid basal

epithelioma component contains HPV 16 DNA as demonstrated by

a punctate nuclear reaction product in the in situ hybridization

preparation. The carcinomatous components were similarly posi-

tive (not shown).

cell origin, by demonstrating the potential of these invasive

components to undergo divergent differentiation [3,4].

Acknowledgments

The authors thank Keerti V. Shah, MD, DrPH, Depart-

ment of Molecular Microbiology and Immunology, Johns

Hopkins Bloomberg School of Public Health, for providing

the PCR analysis.

References

[1] Baggish MS, Woodruff JD. Adenoid basal lesions of the cervix.

Obstet Gynecol 1971;37:807-19.

[2] Baggish MS, Woodruff JD. Adenoid-basal carcinoma of the cervix.

Obstet Gynecol 1966;28:213-8.

[3] Grayson W, Taylor LF, Cooper K. Adenoid cystic and adenoid basal

carcinoma of the uterine cervix: comparative morphologic, mucin, and

immunohistochemical profile of two rare neoplasms of putative

breserve cellQ origin. Am J Surg Pathol 1999;23:448-58.


[4] Grayson W, Taylor LF, Cooper K. Adenoid basal carcinoma of the

uterine cervix: detection of integrated human papillomavirus in a rare

tumor of putative breserve cellQ origin. Int J Gynecol Pathol

1997;16:307-12.

[5] Jones MW, Kounelis S, Papadaki H, et al. The origin and molecular

characterization of adenoid basal carcinoma of the uterine cervix. Int J

Gynecol Pathol 1997;16:301 -6.

[6] Van Dinh T, Woodruff JD. Adenoid cystic and adenoid basal

carcinomas of the cervix. Obstet Gynecol 1985;65:705 -9.

[7] Cviko A, Briem B, Granter SR, et al. Adenoid basal carcinomas of the

cervix: a unique morphological evolution with cell cycle correlates.

Hum Pathol 2000;31:740 -4.

[8] Ferry JA, Scully RE. bAdenoid cysticQ carcinoma and adenoid basal

carcinoma of the uterine cervix. A study of 28 cases. Am J Surg

Pathol 1988;12:134-44.

[9] Brainard JA, Hart WR. Adenoid basal epitheliomas of the uterine

cervix. A reevaluation of distinctive cervical basaloid lesions currently

classified as adenoid basal carcinoma and adenoid basal hyperplasia.

Am J Surg Pathol 1998;22:965 -75.

[10] Clement PB, Zubovits JT, Young RH, et al. Malignant mullerian

mixed tumors of the uterine cervix: a report of nine cases of a

neoplasm with morphology often different from its counterpart in the

corpus. Int J Gynecol Pathol 1998;17:211-22.

[11] Grayson W, Taylor LF, Cooper K. Carcinosarcoma of the uterine

cervix: a report of eight cases with immunohistochemical analysis and

evaluation of human papillomavirus status. Am J Surg Pathol

2001;25:338 -47.

[12] Takeshima Y, Amatya VJ, Nakayori F, et al. Co-existent carcinosar-

coma and adenoid basal carcinoma of the uterine cervix and

correlation with human papillomavirus infection. Int J Gynecol Pathol

2002;21:186 -90.

[13] Gravitt PE, Peyton CL, Alessi TQ, et al. Improved amplification

of genital human papillomaviruses. J Clin Microbiol 2000;38:

357-61.

[14] Daroca Jr PJ, Dhurandhar HN. Basaloid carcinoma of uterine cervix.

Am J Surg Pathol 1980;4:235-9.

[15] Samaratunga H, Beresford A, Davison A. Squamous cell carcinoma in

situ involving mesonephric remnants. A potential diagnostic pitfall.

Am J Surg Pathol 1994;18:1265-9.

[16] Albores-Saavedra J, Manivel C, Mora A, et al. The solid variant of

adenoid cystic carcinoma of the cervix. Int J Gynecol Pathol

1992;11:2 -10.

[17] Grayson W, Cooper K. Adenoid basal epithelioma versus adenoid

basal carcinoma. Am J Surg Pathol 2000;24:313-4.

[18] Grayson W, Taylor L, Cooper K. Detection of integrated high-risk

human papillomavirus in adenoid cystic carcinoma of the uterine

cervix. J Clin Pathol 1996;49:805-9.

[19] Masumoto N, Fujii T, Ishikawa M, et al. P16 overexpression and

human papillomavirus infection in small cell carcinoma of the uterine

cervix. Hum Pathol 2003;34:778 -83.

[20] Klaes R, Friedrich T, Spitkovsky D, et al. Overexpression of

p16(INK4A) as a specific marker for dysplastic and neoplas-

tic epithelial cells of the cervix uteri. Int J Cancer 2001;92:

276-84.

[21] Sano T, Oyama T, Kashiwabara K, et al. Expression status of p16

protein is associated with human papillomavirus oncogenic

potential in cervical and genital lesions. Am J Pathol 1998;153:

1741-8.

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Cervical adenoid basal tumors comprised of adenoid basal