Cloacogenic Adenocarcinoma of the Vulva: A Case Report and Review of the Literature
Merih TEPEOĐLU1, Halit ÜNER2, A.Nihan HABERAL1, Özlem ÖZEN1, Esra KUŢÇU3
1Department of Pathology, Baţkent University School of Medicine, Ankara, Turkey
2Hacettepe University School of Medicine, Ankara, Turkey
3Department of Obstetrics and Gynecology, Baţkent University School of Medicine, Ankara, Turkey
Keywords: Vulvar neoplasms, Adenocarcinoma, Cloacogenic, Metastasis
Primary adenocarcinoma of the vulva, unrelated to the native glands of perineum is an extremely rare neoplasm. Despite awareness of this lesion
for over 40 years, the origin is not beyond speculation. The most reasonable hypothesis is based on the remnants of cloacal differentiation during
early days of life. Here we report the case of a 60-year-old patient with a vulvar mass, who underwent partial vulvectomy and bilateral regional
lymph node dissection. The tumor was composed of papillary and complex glandular structures and exhibited diffuse positivity for cytokeratin
20 and polyclonal CEA, CDX2, and focal positivity with cytokeratin 7. Unlike the indolent behavior of this malignant neoplasm according to the
literature, we found two metastatic inguinal lymph nodes. She did not receive adjuvant therapy and is still alive, free of disease 38 months after
surgery. We present different aspects of vulvar adenocarcinomas with a case report.
Malignant tumors of vulva make up about %4 of all
gynecologic cancers and squamous cell carcinoma comprise
95% of them. Primary adenocarcinomas of the vulva are
relatively rare and mostly originate from Bartholin's glands
(1,2). Colonic type adenocarcinoma is an extremely rare
variant of vulvar adenocarcinoma and few cases have
been reported since 1969 (3). The origin of these tumors
is still controversial. It is suggested that they arise from
cloacal remnants. Novak and Woodruff (2) proposed
that misplaced cloacal remnants could be seen within the
vulvar vestibule and the hypothesis that such misplaced
remnants may undergo malignant transformation into an
adenocarcinoma of the colonic type was suggested later by
Tiltman and Knutzen (4). In the present study, we report a
case of cloacogenic adenocarcinoma of vulva and we also
discuss the pertinent published reports.
A post menopausal 60-year-old woman had a 9-month
history of vulvar discomfort and bleeding. She had
unremarkable medical history. Physical examination
revealed a solitary, red, 2 cm in diameter tumor in the
left labium minus, close to the urethral meatus. No other
visible lesions of the vulva, vagina or perineum were
found. The uterus was small and adnexial structures
were not palpable. Shaving biopsy of the vulvar tumor showed an adenocarcinoma of colonic type. Postoperative
mammography, colonoscopy and PET scan findings
were negative for a primary neoplasm. The subsequent
operation was partial vulvectomy and dissection of bilateral
superficial inguinal lymph nodes.
Resection material consisted of a minor labial fold and
adjacent tissues measuring 4.5 x 2.8 x 1.5 cm, with 2 cm
ulcerated nodular reddish lesion that microscopically
revealed a papillary tumor, reminiscent of a colonic
adenocarcinoma. The neoplastic epithelium was in
continuity with the surface epidermis (Figure 1). The
tumor was composed of papillary and complex glandular
structures lined by large columnar cells with hyperchromatic
nuclei. Many cells were containing intracytoplasmic mucin
and rare goblet cells were seen (Figure 2). The depth
of invasion was measured as 0.8 cm. Lateral and deep
margins were free of tumor. Intracytoplasmic mucin was
demonstrated with staining for Alcian blue histochemistry.
Immunohistochemical analysis exhibited diffuse positivity
for cytokeratin 20, polyclonal CEA and CDX2 (Figure
3). Only focal positivity was seen for cytokeratin 7. No
immunoreactivity was observed for WT-1 and GCDFP-15.
Two of the 23 regional lymph nodes were metastatic with
the tumor. The size of the metastatic focus was 15 mm in
one of the positive lymph node and 2 mm in the other one.
She did not receive adjuvant therapy. She is still alive and
free of disease 38 months after surgery.
Click Here to Zoom
|Figure 1: Adenocarcinoma arising in direct continuity with
surface epidermis (H&E; x20).
Click Here to Zoom
|Figure 2: Higher magnification shows complex glandular
structures lined by large columnar cells with hyperchromatic
nuclei and containing intracytoplasmic mucin (H&E; x40).
Click Here to Zoom
|Figure 3: Tumor cells show intranuclear staining for CDX2
antigen by immunohistochemistry (CDX2; x40).
Primary adenocarcinomas of the vulva are rare tumors
while colonic types of these are exceptional (1-4). To the
best of our knowledge, this is the ninth case ever published
(4-10). Vulvar adenocarcinomas commonly originate
from Bartholin's, sweat or vestibular glands or are more
commonly derived from other systems; i.e. metastasis
(8-11). It is postulated that the vestibular portion of
vulva is derived from cloacal tissue that contains sigmoid
colon and rectum of the hindgut (7,8). This tissue retains
the ability to undergo malignant transformation with
differentiation into an adenocarcinoma similar to a primary
adenocarcinoma of colon (3,6). The histopathological
and immunohistochemical features of these tumors are
similar to those of a large intestinal adenocarcinoma. The
possibility of metastasis, especially from the large intestine,
must be ruled out by clinical work-up and also PET scan.
The treatment of these tumors is radical vulvectomy or
wide local excision with bilateral lymph node dissection.
The clinical behavior is considered to be of indolent nature
after surgery (5-8).
Similar lesions can also be seen in vagina (12). Although
their origin is still the subject of speculation, the most
commonly accepted notion is derivation from cloacal
remnants, like vulvar lesions (12). These lesions can occur
anywhere in the vagina but are most common in the
lower posterior vagina (12). Exclusion of a metastasis to
the vagina should also be undertaken before diagnosing a
primary vaginal-type adenocarcinoma.
In our case, probable metastasis was excluded by PET
scan and complete clinical workup. Detailed evaluation
of the gastrointestinal tract, breast and lung showed no
evidence of a primary tumor. Bartholin's or other gland
adenocarcinoma was ruled out by the location of far from
vestibule, close to the urethral meatus, and the absence
of any native Bartholin's gland adjacent to the tumor.
The final diagnosis was therefore cloacogenic mucinous
adenocarcinoma with regard to the histopathological
and immunohistochemical findings. Strong cytokeratin
20 and weak cytokeratin 7 expression favoured the
diagnosis. Additional polyclonal CEA and CDX2
positivity was consistent with the diagnosis of colonic type
adenocarcinoma as reported in the previous cases (7,11).
The published reports on tumors developing from
cloacogenic remnants within the vulva consist mainly
of single case reports. Tiltman and Knutzen (4) reported
the first case of cloacogenic adenocarcinoma and they
mentioned that the cell origin of this adenocarcinoma was
a misplaced cloacal remnant. After Tiltman, Lee et al. (5)
reported a case of multicentric cloacogenic carcinoma of
the perianal skin and vulva. Kennedy and Majmudar (6)
published two cases of primary adenocarcinomas of vulva
and repeated that the possible origin was cloacal structures.
Furthermore, Willen et al., Zaidi and Conner, Liu et al.
and Dube et al. presented case reports of primary vulvar
cloacogenic adenocarcinomas (7-10). Cloacogenic-derived
adenocarcinomas are most often seen in postmenopausal
women, but premenopausal cases have been reported (8).
The mean age of the patients reported was 51 years (range
between 38-63 years). In the majority of these cases, tumors
ranged in size from 1 to 2 cm largest diameter. In all the cases described, the clinical behavior of this rare tumor
was quite indolent and overall survival was excellent after
radical vulvectomy or wide total excision. Bilateral inguinal
lymph node dissection has been performed in four of the
reported cases (4,8-10) and only one showed ipsilateral
metastasis (4). In our case, metastatic adenocarcinoma was
found in two of bilateral inguinal lymph nodes sampled.
Therefore, in our opinion, ipsilateral or bilateral inguinal
lymph node dissection is indicated. The summary of
clinical features and management of these patients can be
seen in Table I.
In conclusion, knowledge of cloacogenic vulvar
adenocarcinomas is very limited due to the small number
of cases. A cloacogenic origin should be considered in
intestinal-like or mucinous neoplasms. Nodal metastasis
should always be kept in mind both in clinical and
CONFLICT OF INTEREST
The authors declared no conflict of interest
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