The overall annual incidence of melanoma of the female genital tract is less than 0.2 per 100,000 women. Of these, the majority arise in vulvar skin, accounting for 3-7% of melanomas in women.[
11] Primary cervicovaginal malignant melanomas are uncommon tumors comprising approximately 2-5% of female genital tract melanomas. Fewer than 250 cases of vaginal melanomas and 60 cases of cervical melanomas have been reported to date.[
11] Nigogosyan
et al. described the presence of melanoblasts in vaginal mucosa in 3% of women, which could theoretically explain the origin of melanomas in this location.[
12] Blue nevi in the cervix and vagina have also been described.[
13,
14] In our study, most cases had deeply invasive tumors with a mean modified Breslow's thickness of >9.54 mm, which is significantly higher than the 2.91 mm recorded in a series of 19 cases of vaginal melanoma by Chung
et al.[
10] However, the Chung level of invasion was IV/V in all of our cases, similar to that observed by the authors in their study.[
10]
Vaginal melanomas are typically seen in postmenopausal women with a peak incidence in the sixth and seventh decades.[
15] Cervical melanomas, on the other hand, have been reported in a wider age distribution at diagnosis, ranging from 20 to 78 years.[
16,
17] In our study, the median age at diagnosis for vaginal melanomas was 70 years, and the two patients with cervical melanomas were 50 and 72 years of age. Vaginal melanomas do not appear to exhibit a racial predisposition, in contrast to vulvar melanomas, which preferentially affect Caucasian women.[
18] Only one of the patients in this series was of African descent. Similar to previous studies,[
13,
14]
abnormal vaginal bleeding associated with tumor surface ulceration was the most common presenting symptom. Ulceration in these tumors likely contributes to the bloodstained tumor diathesis identified in the cytologic specimens. The presence of ulceration, however, does not necessarily increase the likelihood of obtaining exfoliated tumor cells, as has been suggested by some authors.[
19] Medek
et al. reported a case of an ulcerated oral melanoma that did not shed melanoma cells in a cytologic preparation until the tumor had been traumatized by needle aspiration.[
20]
The diagnosis of melanoma was established on concomitant cytologic and biopsy material obtained in most of our cases. However, melanoma in this location may first be detected on a Pap test. Most of the case reports in the literature describing the cytological findings of melanoma in the lower female genital tract were based on conventional Pap smears []. In fact, the only case series published in 1974 by Masubuchi
et al., describing the cytopathology of malignant melanoma of the vagina, involved conventional Pap tests.[
21] We intended to compare the cytological features of cervicovaginal melanomas identified in liquid-based Pap tests compared to those seen in conventional Pap smear preparations. The small study size in our series of this rare neoplasm, including previously published cases, makes it difficult to compare the sensitivity and specificity of these two techniques reliably. Nevertheless, we did not find any morphological advantage with ThinPrep Pap tests. Whereas melanoma cells are typically described as dyshesive and isolated on smears,[
19] in the present study they were also observed forming clusters in each Pap test type. Several clusters with overlapping cells were difficult to interpret. Prominent nucleoli are a well-recognized cytomorphological feature of melanoma cells[
7,
8,
21–
25] and were seen in all cases of the present study. Melanin pigment, when present, is a helpful finding in differentiating melanoma from other high-grade tumors such as poorly differentiated carcinoma, sarcoma, and anaplastic lymphoma. However, melanin may be focal and not represented in Pap test material or could be absent in the case of an amelanotic melanoma. It is unclear why melanin pigment was identified in only three of the ThinPrep cases of this study. Nuclear pseudo-inclusions (also called Apitz bodies), considered to be one of the characteristic features of melanoma,[
21] were only seen in one conventional Pap smear. Most other investigators have similarly not been able to identify these nuclear inclusions in cytological smears.[
7,
8,
23–
25] While ThinPrep Pap tests did not provide a morphological advantage over conventional smears, liquid-based cytology specimens did offer additional material for cell block preparation and immunocytochemical evaluation in a subset of our cases. The advantages of cell block preparation and immunocytochemistry performed on procured cytology material has been demonstrated by several investigators.[
26] Cell blocks and immunocytochemistry were utilized as adjuncts to confirm a diagnosis of malignant melanoma in three cases.
| Table 2Summary of previously reported and current study cytomorphological features of cervicovaginal melanoma |
In summary, we present to the best of our knowledge the largest cytopathology series of six cervicovaginal melanomas, comparing liquid-based cytology with conventional Pap tests. These mucosal melanomas frequently present as ulcerated masses, resulting in high cellularity with characteristic melanoma tumor cells, even on conventional Pap tests. Although the number of cases reported in the series is limited, the type of preparation method (conventional, Thinprep) did not appear to confer a cytomorphological advantage with respect to making a diagnosis of melanoma. ThinPrep cases, however, did impart the advantage of additional material for cell block preparation and immunocytochemistry.