Unusually aggressive primary cloacogenic carcinoma of the vulva: A case report and literature review

doi:10.4236/crcm.2013.25081

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Vol.2, No.5, 302-305 (2013) Case Reports in Clinical Medicine

http://dx.doi.org/10.4236/crcm.2013.25081

Unusually aggressive primary cloacogenic

carcinoma of the vulva: A case report and

literature review

Rajni Chibbar1, Kimberly A. Wood2, Christopher K. Giede3, Anit a Agrawal4*

1Department of Pathology, University of Saskatchewan, Saskatoon, Canada

2College of Medicine, University of Saskatchewan, Saskatoon, Canada

3Department of Obstetrics and Gynecology, Royal University Hospital, Saskatoon, Canada

4Department of Obstetrics and Gynecology, University of Saskatchewan, Saskatoon, Canada;

*Corresponding Author: [email protected]

Received 11 November 2012; revised 8 December 2012; accepted 12 January 2013

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Vulvar cancer is an uncommon tumor and re-

presents 3% - 5% of all female genital tract ma-

lignancies. The overall incidence is 1.5/100,000

women. Hi stop a thologi cally the v ast m ajori ty (90% )

are squamous cell carcinomas. Primary cloaco-

genic carcinoma of the vulva is extremely rare

with less than 20 cases reported in English lit-

erature [1]. The se tumors are though t to arise from

embryonic or ectopic rest s of cloacog enic tissue.

The majority of these reported ca ses is relativ ely

indolent cancer , only one case of cloacogenic car-

cinoma of the vulva reported metastatic spread

to the inguinal lymph nodes and none that de-

scribe distant metastases. Here we present an

aggressive and diagnostically challenging case

of cloacogenic carcinoma of the vulva and a re-

view of current literature to date.

Keywords: Cloacogenic Vulvar Cancer; Me tas tasis

1. INTRODUCTION

Primary cancer of the vulva is rare accounting for only

3% - 5% of all lower female genital tract cancers. Pri-

mary cloacogenic carcinoma of the vulva is extremely

rare with less than 20 cases reported in English literature

[1]. Only one case reported metastatic spread to inguinal

lymph nodes and none that describe distant metastases.

These tumors are thought to arise from embryonic or ec-

topic rests of cloacogenic tissue. Here we present a case

of primary cloacogenic carcinoma of the vulva which

metastasized to the lungs and bilaterally to inguinal and

pelvic lymph nodes at initial presentation.

2. CASE REPORT

A 49-year-old nulligravida postmenopausal woman

presented in March of 2010, with multiple small vulvar

lesions an accompanying three weeks history of pain,

pressure on vulva, bleeding, pruritus and swelling. Phy-

sical examination revealed severe swelling and multiple

erythematous tender small nodules less than 1 cm in size

on the vulva and lower vaginal canal and palpable lymph

nodes in the right groin (Figure 1(A)).

Magnetic resonance imaging (MRI) of the pelvis showed

a 3.8 × 3.4 cm lobular heterogeneously enhancing mass

located in the lower region of the vaginal canal and vulva.

CT scan reported spread to the lung and inguinal and

pelvic lymph nodes with bilateral heterogeneously en-

hancing multi-lobulated masses in the groin measuring

6.1 × 5.9 cm in the right, and 4.8 × 5.0 cm in the left.

Punch biopsies of the left vulva reported moderately dif-

ferentiated adenocarcinoma with a depth of invasion of

3.74 mm (Figure 1(B)). Lymphovascular space invasion

was noted. A non-neoplastic, slightly dilated gland lined

by non-neoplastic columnar epithelium and goblet cells

was present within the overlying squamous epithelium.

On immunohistochemistry neoplastic cells were high-

lighted with cytokeratin (CK) 20 (Figure 1(C)), CDX-2

(Figure 1(D)), carcinoembryonic antigen (CEA) and p53.

Mucicarmine stain was positive. Neoplastic cells were

negative with CK7, estrogen receptor (ER), progesterone

receptor (PR), Wilm’s tumor-1 (WT-1), p16, vimentin

and S-100 antibodies. Based on histology and immune

profiling a metastatic from the gastrointestinal tract was

suggested. Clinical evalu ation of the gastrointestinal tract

R. Chibbar et al. / Case Reports in Clinical Medicine 2 (2013) 302-305 303

Figure 1. (A) Gross appearance of lesions on

vulva; (B) Low power (H & E ×4) of lesion

present on excisional biopsy of vulva and lym-

phovascular invasion (arrow); (C) CDX-2 nu-

clear staining of neoplastic cells; (D) CK-7 cy-

toplasmic staining for neoplastic cells and non-

neoplastic gland (*).

by colonscopy and computer topography (CT) showed

no pathology.

The vulvar cancer was treated urgently with radical

concurrent chemo-radiation over 43 days. After comple-

tion she underwent bilateral inguinal lymph node de-

bulking. Residual vulvar tumor, persistent enlarged pel-

vic lymph nodes, and lung lesions were noted in a sub-

sequent CT follow up and she was treated with car-

boplatin-paclitaxel as a second line chemotherapy for 6

cycles. After that bilateral external iliac lymph node de-

bulking was carried out for persistent pelvic lymph nodes

and histopathology reported viable tumor cells. In all

three histopathology specimens from various procedures,

neoplastic cells had a striking resemblance to colonic

adenocarcinoma and a diagnosis of cloacogenic carcino-

ma was made. The patient was treated with FOLFIRI

chemotherapy for three cycles with no response and was

then advised for no further chemotherapy. She was re-

ferred to palliative services for pain control and she died

after 27 months of initial diagnosis.

3. DISCUSSION

Only a few cases have reported adenocarcinoma aris-

ing from cloacal remnants. The average age of women

reported with cloacogenic tumors of the vulva or lower

genital tract was 51 years old and ranged from 35 to 67

years of age. Majority of the cases (Table 1) described

solitary tumors that ranged in size from 1.0 to 2.0 cm

largest diameter, presenting on the external urethral mea-

tus [2], labia majora [3], posterior vulva [4], posterior

fourchette [4-6], Bartholin’s gland [1], vagina [7] and

cervix [7]. One case describes multiple tumors ranging in

size from 0.1 to 1.4 cm on posterior to the fourchette [8].

Cell origin of these tumours is still unclear but it has

been proposed that they arise from remnant cells of the

cloacal membrane [2,6-8]. During the fourth to sixth

week of gestation the urorectal septum partitions the

cloaca into the primitive urogenital sinus ventrally and

the anal canal dorsally [9]. Distally, the urorectal septum

comes into contact with the anal membrane in this area

and forms the perineum. The anal pit is formed from pro-

liferating mesenchymal cells around the anal membrane.

The anal canal becomes patent around the seventh to

eighth week of gestation when the anal membrane rup-

tures creating a zone of separation that is demonstrated

by an irregular folding of the adult mucosa, the pectinate

line.

The primitive urogenital sinus consists of three areas.

The superior portion expands to derive the bladder, the

narrow middle portion forms the pelvic urethra and the

inferior portion expands to form the definitive urogenital

sinus [9]. The definitive urogenital sinus is enclosed by

the urogenital membrane and goes on to form the endo-

derm-lined urethral groove, and later on the vestibule.

Externally, a pair of swellings adjacent to the urogenital

membrane forms the cloacal folds (the urogenital folds)

and the labioscrotal folds, which go on to form the labia

minoria and labia majoria, respectively. In the seventh

week of gestation the urogenital membrane ruptures cre-

R. Chibbar et al. / Case Reports in Clinical Medicine 2 (2013) 302-305

304

Table 1. Summary of clinical presentations and management of 12 patients.

Author Age Lesion type

Lymph node

metastasis Distant

metastasis Treatment Prognosis (months)

Lui et al., 2002, [1] 49 Left labia minora No No WLE/UL IFLND AWH at 24 months

Tiltman et al., 1978, [2] 50 External urinary meatus Yes No Modified radical

Vulvectomy and B/L IFLND NA

Dube et al., 2004, [3] 58 Right labia majora No No Right hemivulvectomy and

UL IFLND AWH at 16 months

Kennedy et al., 1993, [4] 54

Left Posterior vulva

Posterior fourchette No No

Radical vulvectomy and B/L

IFLND

WLE

10 years (died of

urosepsis)

AWH at 4 years

Ghamande et al ., 1995, [5] 67 Posterior fourchette No No Radical vulvectomy and

B/L IFLND NA

Willen et al., 1998, [6] 57 Left posterior vestibulumNo No WLE AWH at 26 months

Fox et al., 1988, [7] 35, 43, 59Vaginal vault

Zaidi et al., 2001, [8] 43 Posterior fourchette No No Partial posterior vulvectomy AWH at 18 months

Lee et al., 1990, [11] 27 Multifocal No

ating a patent urogen ital sinus. Therefore in the vestibule

and the labia minora, remnants of cloacal membrane

could persist and give rise to cloacogenic carcinoma of

the vulva. Remnants of cloacal membrane persist proxi-

mal to the pectinate line from where transitional cell

cloacogenic carcinoma can arise [10].

Treatment for the majority of the cases presented was

radical vulvectomy and bilateral local lymph node exci-

sion [2,4,5,8], with the more recent cases pursuing local

excision with bilateral local lymph node excision [1,3,6].

In the majority of the cases the tumor did not metasta-

sized and was referred to as indolent in nature and exci-

sion of the lesion(s) appeared to be curative[1,3-5,7,8]

however Willen et al. [6] reported recurrence of the tu-

mor one year later, and performed a wider resection of

the tumor. Our case, the tumor was aggressive in nature

with metastatic spread to inguinal and pelvic lymph

nodes and the lung. Complete excision of the tumor was

not possible in this case due the extent of tumor in-

volvement and metastasis and therefore was initially

treated with concurrent chemo-radiation therapy. Patient

had partial response to the treatment with some tumor

regression and pain relief, but the neoplastic cells re-

mained viable in the vulvar lesions after therapy was

completed. Patient then received second line carboplatin-

paclitaxel chemotherapy for persistent metastatic disease

after initial treatment. The other reported case of metas-

tatic spread to local lymph node, excision only was re-

quired for treatment and patient was reported to be doing

well one year after [2].

The majority of the cases reported a single tumor aris-

ing in direct continuity with the surface epithelium [1-6].

The tumor in our case was multifocal and it was difficult

to assess if the tumors arose in continuity with or beneath

the surface epithelium as only two punch and one ex-

isional biopsy of the vulva where evaluated, where other

cases examine tissue from complete or partial vulvec-

tomy. Fox et al. [7] describe a tumor originating in the

vagina vault that had similar microscopic appearance as

the tumor described here, with the lesion presenting be-

neath an ulcerated overlying epithelium. Zaidi and Con-

ner [8] reported a case of multiple surface nodules in

direct continuity with the surface epithelium that was

focally ulcerated.

Metastatic adenocarcinoma of the vulva was consid-

ered initially as the lesions had many characteristics of a

tumor derived from enteric origin however this was ex-

cluded as there was no evidence of a previous or concur-

rent primary tumor of similar histological appearance.

Also metastatic spread to the pelvic and inguinal lymph

nodes did not consist with a primary colonic adenocar-

cinoma but was in keeping with a primary carcinoma of

the vulva. Therefore, primary cloacogenic carcinoma was

determined in this case due to morphological appearance

and immune-histochemistry staining of the neoplastic

cells along with pattern of metastatic spread. Neoplastic

cells had a striking resemblance to colonic adenocarci-

noma with the presence of one non-neoplastic gland. The

presence of non-neoplastic glands was remarked by oth-

ers [2,3,6,8].

4. CONCLUSION

Primary cloacogenic carcinoma of the vulva is very

rare but it is important for pathologists and clinicians to

be aware of. Any lesion seen on the vulva and perineum

should be biopsied at its earliest and have a pathology

review for diagnosis confirmation. Detailed clinical work-

up and careful histopathological examination using histo-

pathology and immune-histochemistry is necessary to

make the early diagnosis and less radical management. It

is considered to be of indolent nature but in the case of

R. Chibbar et al. / Case Reports in Clinical Medicine 2 (2013) 302-305 305

our case it acted aggressively despite radical treatment.

Therefore, early recognition and wide local excision of

the tumor(s) prior to metastatic spread is important for

favourable prognosis and decreased reoccurrence.

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