Primary melanocytic tumours of the uterine cervix are rare. These include blue nevi and malignant melanoma. Blue nevi are benign melanocytic lesions which occur as incidental finding. Primary cervical melanomas are rare mucosal melanomas with aggressive behaviour. In small biopsies, they can mimic poorly differentiated carcinomas. Here we present the cases of melanocytic tumours reported from our institute during the last 6 years
Melanocytic tumours of the uterine cervix are rare [
We received 3416 hysterectomy specimens in the department of pathology, Amrita Institute, Kochi, during the last 6 years, from the departments of Surgical oncology and Gynaecology. There were 3 cases of common blue nevi. All the 3 patients were in the perimenopausal age group (42 - 51 yrs) and underwent hysterectomy for fibroids. Grossly cervixes were unremarkable in 2, and showed congestion in one. Microscopically all 3 cases showed cervix with unremarkable ecto cervical epithelium. Sub epithelium showed scattered spindly/elongated cells with moderate cytoplasm and uniform round/oval nuclei. Cytoplasm showed brownish black pigment granules, which were removed with Melanin bleach. Iron stain was negative. None of the patients had co existing melanomas.
A 62 year old female presented with complaints of postmenopausal bleeding of 2 wks duration .Pelvic examination revealed a large exophytic growth involving the entire cervix, extending to parametrium. Cervical punch biopsy was done, which showed fragmented tissue with ulcerated epithelium and an infiltrating neoplasm composed of cells arranged in diffuse pattern with scanty intervening stroma. No individual cell keratinisation/kera- tin pearls/cytoplasmic pigments were seen. Diagnosis of a non keratinizing large cell squamous cell carcinoma was offered. Subsequently, the patient received concurrent chemo radiation followed by brachytherapy. After one month of completing radiation pelvic examination revealed residual disease without parametrial extension. Radical hysterectomy was done, with bilateral pelvic lymph node dissection. Hysterectomy specimen showed an irregular grey white growth with heamorrhagic areas involving the cervix and measuring 4.7 cm in maximum dimension. On microscopic examination, sections from cervix showed ecto cervical epithelium with focal ulceration and an underlying neoplasm composed of similar cells as in small biopsy. There was focal junctional activity. In addition, were seen sheets of spindly/epithelioid cells with abundant brownish pigment in the cytoplasm (removed with Melanin bleach). A Masson Fontana stain was done in the previous small biopsy, which revealed the melanin pigment in many of the cells. Immuno histo chemistry showed the neoplastic cells to be positive for S100 and HMB 45 (
The origin of melanocytes in the Mullerian tract is still debated. There are different theories regarding their ori-
gin. One of the theories is that melanocytic precursors migrate aberrantly during embryogenesis towards the mullerian epithelium [
Melanocytic lesions are described in extracutaneous sites like oral and esophageal mucosa, maxillary sinus, conjunctiva, meninges, vagina etc [
Primary mucosal melanomas represent only about 1.4% of all melanomas with higher rates among women compared to men (may be because of increased incidence of genital melanomas) [
Norris and Taylor [
1) Absence of melanoma elsewhere in the body,
2) Demonstration of junctional activity in the cervix,
3) Metastasis according to the pattern of cervical carcinoma.
Among the 88, only 26 cases showed junctional activity. This may be due the fact that, most often, the overlying epithelium is ulcerated. Melanin pigment is seen within the cytoplasm of neoplastic cells in most of the cases. But in 15 cases, pigment was absent in the initial small biopsy or excision making the diagnosis difficult. In such cases, the differential diagnoses included poorly differentiated carcinoma, sarcoma or lymphoma, warranting a panel of immunohistochemical stains to arrive at a definite diagnosis. Literature gives a small series of cases of amelanotic melanomas initially misdiagnosed as anaplastic carcinoma, clear cell carcinoma, chorioepithelioma, sarcoma and lymphoma [
No. | Case | Junctional activity | Melanin pigment in cells | Surgery | Chemo therapy | Radio therapy | Survival |
---|---|---|---|---|---|---|---|
1 | 1889 | No | Not known | Yes | Not known | Not known | Not known |
2 | 1923 | No | Not known | Not known | No | No | <1 year |
3 | 1944 | No | Not known | Yes | No | No | >2 yrs |
4 | 1950 | No | Not known | Yes | No | Yes | <1 year |
5 | 1954 | Not known | Not known | Not known | Not known | Not known | Not known |
6 | 1954 | Present | Not known | Yes | No | Yes | <2 yrs |
7 | 1959 | Not known | Not known | Yes | No | Yes | <2 yrs |
8 | 1959 | Present | Not known | No | No | Yes | <1 yr |
9 | 1961 | Present | Not known | Yes | No | No | Not known |
10 | 1961 | Present | Not known | No | No | Yes | <1 yr |
11 | 1966 | Not known | Present | Yes | No | Yes | <2 yrs |
12 | 1967 | Present | Present | No | No | Yes | Not known |
13 | 1967 | Not known | Not known | Yes | No | Yes | 1 yr |
14 | 1970 | Not known | Not known | Yes | No | Yes | >1 yr |
15 | 1970 | Not known | Present | Yes | No | Yes | >1 yr |
16 | 1971 | Present | Present | Yes | Yes | Yes | >1 yr |
17 | 1976 | No | Present | Yes | Yes | Yes | <1 yr |
18 | 1979 | Not known | Not known | Yes | No | No | 1 yr |
19 | 1979 | Not known | Not known | Yes | Yes | Yes | >1 yr |
20 | 1979 | No | Not known | Yes | Yes | No | >1 yr |
21 | 1980 | Present | Present | Yes | No | No | <1 yr |
22 | 1981 | Present | Not known | Yes | Yes | No | <1 yr |
23 | 1981 | Present | No | Yes | No | No | Not known |
24 | 1981 | Present | Present | Yes | No | No | >1 yr |
25 | 1986 | Present | Present | Yes | No | No | >1 yr |
26 | 1987 | No | No | Yes | No | Yes | <1 yr |
27 | 1988 | Not known | Present | No | Yes | Yes | not known |
28 | 1988 | Not known | Present | No | No | Yes | <1 yr |
29 | 1989 | Not known | Present | Yes | No | Yes | >1 yr |
30 | 1989 | Not known | Present | Yes | Yes | No | <1 yr |
31 | 1990 | Present | Present | Yes | No | Yes | >1 yr |
32 | 1990 | Present | Present | Yes | No | No | Not known |
33 | 1990 | Present | Present | Yes | No | No | >1 yr |
34 | 1991 | Not known | Present | Yes | No | Yes | >1 yr |
35 | 1991 | Not known | Not known | Yes | Yes | Yes | <1 yr |
36 | 1992 | Not known | Present | No | No | Yes | >1 yr |
37 | 1992 | Not known | No | Yes | Yes | Yes | 1 yr |
38 | 1992 | Not known | Not known | Yes | No | No | Not known |
39 | 1993 | Not known | Present | Yes | No | Yes | >1 yr |
40 | 1995 | Not known | Present | Yes | No | No | >1 yr |
41 | 1995 | Not known | Not known | Yes | No | No | >1 yr |
42 | 1996 | Present | Not known | Yes | No | Yes | Not known |
43 | 1997 | Not known | Present | Yes | Yes | No | Not known |
---|---|---|---|---|---|---|---|
44 | 1997 | No | No | Yes | Yes | No | >1 yr |
45 | 1998 | Not known | No | No | No | Yes | <1 yr |
46 | 1998 | Present | Present | Yes | No | No | >1 yr |
47 | 1998 | Present | No | Yes | Yes | No | >1 yr |
48 | 1998 | No | Not known | Yes | No | Yes | >1 yr |
49 | 1999 | Not known | Present | Not known | No | Yes | <1 yr |
50 | 1999 | Not known | Present | Yes | No | No | >1 yr |
51 | 1999 | Not known | Present | Yes | Yes | No | <1 yr |
52 | 1999 | Present | Present | Yes | No | Yes | >1 yr |
53 | 1999 | Present | No | Yes | Yes | No | <1 yr |
54 | 2000 | Not known | Present | No | No | Yes | <1 yr |
55 | 2001 | No | No | Yes | No | No | <1 yr |
56 | 2001 | Not known | Present | Yes | No | No | <1 yr |
57 | 2001 | Not known | Present | Yes | No | Yes | 2 yrs |
58 | 2002 | Not known | Not known | Yes | No | No | <1 yr |
59 | 2003 | Not known | Present | Yes | No | No | <1 yr |
60 | 2003 | Not known | Present | Yes | Yes | No | <1 yr |
61 | 2003 | Not known | Present | Yes | Yes | No | <1 yr |
62 | 2004 | Not known | Present | Not known | Not known | Not known | Not known |
63 | 2005 | Not known | Present | Yes | Yes | Yes | <1 yr |
64 | 2005 | Not known | Not known | Not known | Not known | Not known | Not known |
65 | 2005 | Not known | Not known | Yes | Yes | No | >1 yr |
66 | 2005 | Not known | No | Yes | Yes | Yes | 2 yrs |
67 | 2006 | Present | Present | Yes | No | Yes | 2 yrs |
68 | 2007 | Not known | No | Yes | No | No | >1 yr |
69 | 2008 | Present | Present | Yes | Yes | No | >1 yr |
70 | 2009 | Present | Present | Yes | Yes | Yes | >1 yr |
71 | 2009 | Not known | Present | Yes | Yes | Yes | >1 yr |
72 | 2010 | Rajan duggal | Present | No | No | No | Not known |
73 | 2011 Luz | Not known | Present | Yes | No | Yes | >1 yr |
74 | 2012 El Fatemi Hinde | Not known | Not known | No | Yes | No | Not known |
75 | 2012 Ya Ju Tsai | Not known | Not known | Yes | No | Yes | Not known |
76 | 2013 E.Myriokef alitaki | Not known | Not known | Yes | No | No | >1 yr |
77 | 2013 Nilanch ali | Present | Present | Yes | Yes | No | <1 yr |
78 | 2013 Hemalat ha | Present | Present | Not known | Not known | Not known | Not known |
79 | 2013 Not knowny anot known | Present | Present | Not known | Not known | Not known | Not known |
80 | 2013 K J Min | Not known | Not known | Yes | Yes | Yes | >1 yr |
81 | 2014 Preethi bhagel | Not known | Present | Yes | Yes | Yes | <1 yr |
82 | 2014 Zhuqing | No | Present | Yes | Yes | No | >1 yr |
83 | 2014 Deshpande | Not known | Present | Not known | Not known | Not known | Not known |
84 | 2014 Yan Du | Not known | Not known | Not known | Not known | Not known | Not known |
85 | 2014 Shrivastava | No | No | Yes | No | Yes | <1 yr |
86 | 2015 Jessica L Berger | No | No | Yes | Yes | Yes | <1 yr |
87 | 2015 Caglayan Geredeli | Not known | Not known | Yes | Yes | No | <1 yr |
88 | 2015 Kadir Cetinkaya | Present | Present | Yes | Yes | Yes | >1 yr |
89 | Present case | Present | Present | Yes | Yes | Yes | >1 yr |
REF: Cases 1-71―Ref [
The large tumor in the subsequent hysterectomy specimen revealed cytoplasmic melanin. The histochemical stain, Massons Fontana, demonstrate the pigment in amelanotic cases and a Melanin bleach removes the same, from pigmented cells, confirming the nature of the pigment. Immunohistochemical stains used for confirmation are S100, HMB 45 and Melan A. There has been a long debate on the staging system to be followed in primary cervical melanoma. Now it is generally accepted that staging is to be done as per the International Federation of Gynecology and Obstetrics (FIGO) staging system for cervical cancer, and not the Clarks system as the tumor generally follows the same patterns as cervical carcinoma and the FIGO system correlates better with prognosis [
Primary amelanotic melanoma of the female genital tract usually has an even poorer outcome as a consequence of delayed diagnosis and lack of standardized treatment. Compared with amelanotic melanoma of the vulva, disease of the cervix is more likely to be misdiagnosed, identified at a later stage, and has a poorer outcome.
To conclude, we present the cases of cervical melanocytic lesions from our institute, during a period of last 6 years. The blue nevi are extremely rare incidental findings and are detected only in 0.087% of hysterectomies. Only one case of primary cervical melanoma was diagnosed, the initial small biopsy of which was labeled as poorly differentiated carcinoma. This emphasizes the rarity of this tumour and the need of ancillary techniques in accurately diagnosing poorly differentiated tumours especially in small cervical biopsies. Also malignant melanoma should be included in the list of differential diagnoses along with carcinomas and sarcomas in poorly differentiated cervical neoplasms. A detailed review of the literature shows that primary cervical melanoma is a highly aggressive tumour with poor prognosis. A consensus on treatment modalities has not yet been reached. And the overall survival is one year or less in majority of the patients.
Indu R. Nair,Anupama Rajanbabu,Annie Jojo,Shruthi Shivdas,Vijaykumar Kottarathil,K. Radhamany, (2016) Uterine Cervical Melanocytic Tumours—A Single Institution Experience with Review of Literature. Open Journal of Obstetrics and Gynecology,06,280-286. doi: 10.4236/ojog.2016.65035