|Ahead of print publication
Carcinoma cervix de novo with widespread cutaneous/subcutaneous metastasis: A rare case report
Shraddha Raj1, Neha Kakkar2, Prachi Agrawal2, Satya Dutta3, KT Bhowmik2
1 Department of Radiotherapy, IGIMS, Patna, Bihar, India
2 Department of Radiotherapy, VMMC and SJH, New Delhi, India
3 Department of Pathology, VMMC and SJH, New Delhi, India
Department of Radiotherapy, IGIMS, Patna, Bihar
Source of Support: None, Conflict of Interest: None
Cancer of the uterine cervix is one of the leading gynecological malignancies of developing nations including India. A 45-year-old female presented with menstrual irregularities and other nonspecific symptoms. After initial workup, she was diagnosed with carcinoma cervix, Stage IV A, while she was being planned to take up radical concomitant chemoradiotherapy, she developed widespread nodules over various sites over the body, which were histopathologically proven as metastatic lesions. She was treated with a palliative intent by radiotherapy and chemotherapy. Only a few such cases have been reported in the literature with variable outcomes. These rare presentations should be thoroughly worked up and studied to know more about their biological behavior.
Keywords: Breast metastasis, carcinoma cervix, cutaneous metastasis, subcutaneous metastasis, visceral metastasis
|How to cite this URL:|
Raj S, Kakkar N, Agrawal P, Dutta S, Bhowmik K T. Carcinoma cervix de novo with widespread cutaneous/subcutaneous metastasis: A rare case report. J Can Res Ther [Epub ahead of print] [cited 2019 Nov 18]. Available from: http://www.cancerjournal.net/preprintarticle.asp?id=257730
| > Introduction|| |
Carcinoma of the cervix uteri is the most common malignancy among females in many developing nations, but in India, it is only exceeded by cancer breast. There are 1.23 lakh new cancer cervix patients out of a total of approximately 6 lakh female cancer patients in India. The most common histopathology in cervical cancer patients is squamous cell carcinoma, and the most important factor in the etiopathogenesis is HPV infection. Presenting symptoms are generally due to the local disease – bleeding per vagina, menorrhagia, menometrorrhagia, postcoital bleeding, watery/foul-smelling discharge per vagina, etc. Cervical cancer is known to spread locally within the pelvis. Distant metastasis is uncommon at initial diagnosis. Less than 5% of patients present with distant metastasis., In late stages, the most common sites of metastasis are lungs, bone, and liver. The skin and subcutaneous tissue is a very uncommon site for the dissemination of cervical cancer constituting up to 0.1%–2%.,, Only few cases have been reported in the past regarding such metastasis at the time of diagnosis. This rarity of the case has led us to report it.
| > Case Report|| |
A 45-year-old premenopausal female, P3 + 0 presented to us with bleeding per vaginum, postcoital bleeding, and fever for 2 months. Apart from her regular menses, she had intermittent bleeding. The flow was variable with passage of clots. Fever was high grade, more frequently in the evenings, and associated with shivering. She was admitted for relevant investigations and management.
On local examination, there was a 5 cm × 6 cm growth felt in the cervix with extension to both parametria, not reaching up to the pelvic wall with the involvement of the upper third of the vagina. The rectal mucosa was involved with growth on digital per rectal examination as well as proctoscopy. Cystoscopy showed areas of bladder mucosal infiltration making it a Federation of Gynecology and Obstetrics Stage IV A. Chest X-ray and ultrasound abdomen revealed no other abnormality.
Histopathological examination revealed sheets of cells with extensive clear cell change having moderate to abundant clear cytoplasm and large irregular nuclei and occasional mitosis seen. These cells were negative for special stains mucicarmine and immunostaining with MUCIN 1. Both these markers are evaluated to exclude adenocarcinoma. Thus, the report concluded poorly differentiated carcinoma with extensive clear cell change [Figure 1] and [Figure 2].
|Figure 1: H and E shows poorly differentiated carcinoma with clear cell change|
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|Figure 2: Cytological examination shows cluster of cells with high degree of nuclear pleomorphism and scant to moderate cytoplasm|
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All investigations regarding her fever were done; however, none of them directed us to its cause, except for the high vaginal swab that revealed Escherichia coli growth. It was treated locally by antiseptic douching and systemically according to its antibiotic sensitivity; however, the fever did not respond much.
She was planned to be taken up radical concomitant chemoradiotherapy, just before that she complained of a nodule in her upper back. Within a couple of days, she noticed one more nodule below in the dorsolumbar region and also one in the right submandibular region. On clinical palpation, these were hard, mobile, and discrete masses. The fine-needle aspiration cytology of both the swellings revealed a metastatic squamous cell carcinoma. Soon, she developed a nodule in the left breast region and another in the right breast region and one more in the back. All of these came out to be histopathologically, the same entity [Figure 3]. The diagnosis now was advanced carcinoma of the cervix with skin and subcutaneous metastasis.
|Figure 3: Various sites of metastasis (a) Cutaneous nodules in the back-2 in number, left upper, and right lower (b) Subcutaneous nodule over the right angle of mandible (c) Small cutaneous nodule in the right breast and well-defined 4 cm × 4 cm lump in the left breast|
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Due to the prominent local symptoms, we initially took her upon palliative radiotherapy, EBRT to whole pelvis, through AP-PA portals, 30 Gy/10# over 2 weeks, by Co60 machine. She tolerated it well. At the end of the treatment, her local symptoms were relieved. Furthermore, the fever subsided after radiotherapy. However, her skin nodules were rapidly progressing in size. She was then taken up for palliative chemotherapy with paclitaxel and cisplatin. She received one cycle of chemotherapy, but while still under treatment, she succumbed to her illness at home and expired.
| > Discussion|| |
In the present case, special staining with mucicarmine and immunostaining with MUC1 excluded adenocarcinoma and favored squamous cell carcinoma. We excluded a second malignancy of breast on the following points:
Squamous cell carcinoma is rare in the breast (only 0.1%), occurs in the elderly population and is generally associated with aggressive features. According to the criteria defined by Rosen, to diagnose squamous cell carcinoma (SCC) of the breast: (1) >90% of the area was SCC, (2) absence of skin or nipple involvement, and (3) absence of other primary SCC.
The most common sites of cutaneous metastasis are reported to be the lower abdominal wall and lower extremities., Any reference of metastasis to the submandibular region could not be found. To the best of our knowledge, we are reporting cutaneous metastasis in the submandibular region for the first time ever. Furthermore, such widespread cutaneous metastasis in a freshly diagnosed, surgically nonoperated case of carcinoma cervix case was barely found in the search. Skin metastasis in a cervical carcinoma occurs predominantly on tumor recurrences, with metastasis occurring up to 10 years of the initial diagnosis. The time interval from presentation to distant metastases is related to the prognosis.
A review of 1190 patients revealed that the incidence of skin metastasis in Stage 1 is 0.8%, 1.2% in Stage 2 and 3 both, and 4.8% in Stage 4. The incidence of cutaneous metastasis was observed more in the adenocarcinoma and poorly differentiated varieties as compared to the squamous cell carcinomas.
The management of such advanced disease has to be with palliative intent. Combination chemotherapy with paclitaxel and cisplatin has given better results than cisplatin alone. Palliative radiation helps in controlling local symptoms.
The prognosis is very poor in such cases. It is almost considered preterminal event with the time from the diagnosis to death being around 3 months.,,
Agrawal et al. reported a similar case with widespread cutaneous metastasis who succumbed to the illness despite six cycles of palliative chemotherapy.
| > Conclusion|| |
We are reporting an unusual manifestation of metastatic disease in Stage IV carcinoma cervix with even more unusual sites of occurrence. We still need to understand further, the mysterious nature and biology of the tumor. The prognosis of such advanced diseases is grave.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Vinh-Hung V, Bourgain C, Vlastos G, Cserni G, De Ridder M, Storme G, et al
. Prognostic value of histopathology and trends in cervical cancer: A SEER population study. BMC Cancer 2007;7:164.
Sreedevi A, Javed R, Dinesh A. Epidemiology of cervical cancer with special focus on India. Int J Womens Health 2015;7:405-14.
Bellefqih S, Mezouri I, Khalil J, Diakete A, Khanhoussi BE, Tayeb K, et al
. Skin metastasis of cervical cancer: About unusual case. J Clin Case Rep 2013;3:284. Doi: 10.4172/2165-7920.1000284
Elumelu TN, Jatto JB. Distant metastases in uterine cervical cancer patients. JSM Clin Oncol Res 2015;3:1044
Das C, Konar H, Chaudhri P, Phadiker A, Deb AR, Chaudhari S. Skin metastases in genital malignancy. J Obstet Gynecol India 2009;59:563-8.
Brady LW, O'Neill EA, Farber SH. Unusual sites of metastases. Semin Oncol 1977;4:59-64
Brownstein MH, Helwig EB. Patterns of cutaneous metastasis. Arch Dermatol 1972;105: 862-8.
Badge SA, Gangane NM, Shivkumar VB, Sharma SM. Primary squamous cell carcinoma of the breast. Int J Appl Basic Med Res 2014;4:53-5.
Macia M, Ces JA, Becerra E, Novo A. Pure squamous carcinoma of the breast. Report of a case diagnosed by aspiration cytology. Acta Cytol 40 1989;33:201-4.
McCarthy WA, Laucirica R. Cutaneous metastasis from cervical squamous cell carcinoma in a 55 year old women: A rarely reported manifestation. Case Rep Clin Pathol 2014;1:27-32.
Hayes AG, Berry AD 3rd
. Cutaneous metastasis from squamous cell carcinoma of the cervix. J Am Acad Dermatol 1992;26:846-50.
Copas PR, Spann CO, Thoms WW, Horowitz IR. Squamous cell carcinoma of the cervix metastatic to a drain site. Gynecol Oncol 1995;56:102-4.
Basu B, Mukherjee S. Cutaneous metastasis in cancer of the uterine cervix: A case report and review of the literature. J Turk Ger Gynecol Assoc 2013;14:174-7.
Imachi M, Tsukamoto N, Kinoshita S, Nakano H. Skin metastasis from carcinoma of the uterine cervix. Gynecol Oncol 1993;48:349-54.
Moore DH, Blessing JA, McQuellon RP, Thaler HT, Cella D, Benda J, et al
. Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: A gynecologic oncology group study. J Clin Oncol 2004;22:3113-9.
Spanos WJ Jr., Pajak TJ, Emami B, Rubin P, Cooper JS, Russell AH, et al
. 37 Radiation palliation of cervical cancer. J Natl Cancer Inst Monogr 1996;(21):127-30.
Elamurugan TP, Agrawal A, Dinesh R, Aravind R, Naskar D, Kate V, et al
. Palmar cutaneous metastasis from carcinoma cervix. Indian J Dermatol Venereol Leprol 2011;77:252.
] [Full text]
Khurana R, Singh S. Isolated cutaneous metastasis to thigh from cancer cervix- fourteen years after curative radiotherapy. Int J Gynaecol Obstet 2008;11:1-3.
Agrawal A, Yau A, Magliocco A, Chu P. Cutaneous metastatic disease in cervical cancer: A case report. J Obstet Gynaecol Can 2010;32:467-72.
[Figure 1], [Figure 2], [Figure 3]