|Year : 2012 | Volume
| Issue : 2 | Page : 300-302
Multiple cutaneous squamous cell carcinomas: Primary carcinomas versus cutaneous metastasis
Jasleen Kaur1, Nidhi Sharma2, Sanjeev Sharma3
1 Department of Skin and STD, SGRD Medical College, Amritsar, India
2 Department of General Surgery, GND Hospital and Medical College, Amritsar, India
3 Department of Skin and STD, Punjab Civil Medical Services, Punjab, India
|Date of Web Publication||26-Jul-2012|
7 Tara Enclave, Near Mental Hospital, Chownk, Circular Road, Amritsar, -143001, Punjab
Source of Support: None, Conflict of Interest: None
Multiple squamous cell carcinoma (SCC) of the skin is an exceedingly rare entity. It has been reported in a few patients of psoriasis treated with oral psoralen therapy and UV radiation, immunodeficiency states, local intramuscular metastasis and cutaneous metastasis from vulvar SCC. We report the case of a 55-year-old man who reported with a painless non-healing warty growth on the lower back persisting for the last 2 years which was excised. Its histopathology proved it to be SCC with HPV changes. On examination, 4 similar lesions were found on the upper back; out of which 1 lesion exhibited marked dysplastic changes on histopathology, but without HPV changes. This case could be either multicentrically developed SCC due to HPV infection or cutaneous metastasis as carcinoma of unknown primary site i.e. metastasis occurring before primary tumor diagnosis.
Keywords: Carcinoma of unknown primary site, cutaneous, HPV, multiple, squamous cell carcinomas
|How to cite this article:|
Kaur J, Sharma N, Sharma S. Multiple cutaneous squamous cell carcinomas: Primary carcinomas versus cutaneous metastasis. J Can Res Ther 2012;8:300-2
| > Introduction|| |
Cutaneous squamous cell carcinoma (SCC) is the second most common non melanoma skin cancer after basal cell carcinoma. It is generally an indolent disease affecting people over 40 years of age.  Its pathogenesis is multifactorial with ultraviolet (UV) radiation, immunosuppression, HPV infection, precancerous lesions and scars acting as cofactors.  Multiple cutaneous SCC can develop either because of multicentric development of SCC or spread of primary SCC via shelving, conduit spread, local metastasis via lymphatics or disseminated cutaneous metastasis from other malignancies. Although most patients of primary cutaneous SCC have an excellent prognosis, the long-term prognosis of metastatic disease is poor.
| > Case Report|| |
A 55-year-old man presented to the hospital with a painless non-healing warty growth on the lower back. Though it was small in size initially, it gradually increased to its present size in over two years. There was no history of arsenic intake, burns, scars or any other pre-existing skin lesion. Physical examination revealed a non tender raised 3 × 2.5 cm verrucous plaque on the lower back. The surface was rough, scaly, margins well defined, raised with few atrophic areas in between. On inspection, four similar verrucous lesions were observed on the upper back. Their size varied between 0.5 and 1 cm in diameter with rough scaly surface. There were no palpable lymph nodes in the axillary or inguinal region. Past medical history was not significant. Chest X-ray and ultrasound of abdomen were unremarkable.
This was followed by wide local excision of the larger lesion by the surgical team. Histopathology showed total loss of polarity with marked HPV-induced nuclear changes in epidermal cells suggestive of severe dysplasia and mitotic figures seen up to the top layer.
Later on, skin biopsy of smaller lesion revealed marked dysplastic changes with intact basement membrane but without HPV changes suggestive of carcinoma in situ.
The patient was given chemotherapy i.e. five monthly cycles of Inj. Cisplatin and Inj. 5 Flourouracil. The patient is under observation for the last 1 year. All the four smaller lesions regressed within four months of chemotherapy. There is no recurrence of lesions after stopping chemotherapy [Figure 1] and [Figure 2].
| > Discussion|| |
Cutaneous SCC is a malignant tumor of keratinizing epidermal cells. It is the second leading cause of death after melanoma.  The risk factors for SCC include older age, male sex, increased sensitivity to sun exposure, an increased number of precancerous lesion and immunosuppression. 
SCC arises more commonly in sun exposed areas of skin i.e. head, neck and arms but can occur on trunk and buttocks also. UVB radiation damages DNA by inducing the formation of pyrimidine dimmers and induces mutation of p-53 tumor suppressor genes. 
SCC has been commonly reported after immunodeficiency resulting from immunosuppression in organ transplant recipients, patients with HIV infection or leukaemia and in primary immunodeficiency like interferon gama receptor 2 deficiency.  CD4 counts are significantly lower in transplant recipients with cutaneous SCC than in those without such lesions. 
Exposure to oral psoralens,  arsenic, coal tar products, UVA photo chemotherapy and human papilloma virus (HPV) infection has also been associated with SCC. Like in mucosal/anogenital SCC, HPV infection considerably plays an active role in pathogenesis of cutaneous SCC.  Genetic disorders like albinism, epidermodysplasia verruciformis and Xeroderma pigmentosa predispose to SCC.
It is thought to arise as a focal intra-epidermal proliferation from precancerous lesions including actinic keratosis, Bowen's disease, erythroplasia of Queret and arsenical keratosis.
SCC tends to arise in damaged skin e.g. after thermal burns, radiation or in chronic inflammation (chronic ulcers and chronic draining sinuses). 
Thus the pathogenesis of cutaneous SCC can be explained by the combined action of the oncogenic and immunosuppressive effect of UV radiation, HPV infection and immunosuppression.
Cutaneous SCC may spread by 1) expansion and infiltration 2) shelving or skating 3) conduit spread 4) metastasis. SCC grows locally by expansion and infiltration. When the tumor reaches a hard surface (muscle, cartilage, bone) it may spread laterally (shelves/skates) under normal skin along facial or capsular planes, muscle, perichondrium, and periosteum. The spreading of a tumor along the nerve or vessel in the perineural, or perivascular space is called conduit spread. Local metastasis occurs primarily by way of lymphatics initially to the superficial draining lymph nodes, then to the deeper nodes. Distant metastasis occurs by hematogenous dissemination most commonly to the lungs, liver, brain, skin or bone. 
Cutaneous metastases, in general, occur in 0.7% to 9% of all malignancies.  In men younger than 40 years, the most common sources of cutaneous metastases are melanoma, colon cancer, and lung cancer. In men older than 40 years, the most common sources of cutaneous metastases are lung cancer, colon cancer, SCC in the oral cavity, and melanoma. In women, the most common sources of cutaneous metastases are breast cancer, colon carcinoma, and ovarian carcinoma.
Usually, cutaneous metastases develop after the initial diagnosis of the primary malignancy. Sometimes, metastases may be discovered prior to the diagnosis of a primary tumor (e.g. lung and renal cell carcinoma) which is termed as carcinoma of unknown primary site (CUPS). 
In dealing with cutaneous CUPS, the age, the sex, and the affected skin region of the patient as well as the histology of the lesion are important clues that are useful in determining a likely primary tumor. Patients with cutaneous metastasis usually present with rapidly developing nodules or tumors. Mostly asymptomatic but pain and tenderness may be noted. 
The diagnosis of metastised cutaneous SCC hinges on histopathologic evaluation of involved skin. Tumors may show characteristics of the underlying tumor, or they may have a more anaplastic appearance.
Most patients with primary cutaneous SCC have an excellent prognosis but SCC developing as cutaneous metastasis; the long-term prognosis is poor. The degree of cellular differentiation, tumor thickness, location and size also has prognostic value as shown in [Table 1]. 
|Table 1: Influence of tumor variables on local recurrence and metastasis of squamous cell carcinoma.|
Click here to view
In the present case study, the indolent multiple warty lesions developing on non sun-exposed areas with HPV changes in epidermal cells were diagnosed as aggressive multiple SCC due to HPV infection but the possibility of carcinoma of unknown primary site is also considered.
| > References|| |
|1.||Diepgen TL, Mahler V. The epidemiology of skin cancer. Br J Dermatol 2002;146:1-6. |
|2.||Mackie RM. Epiderml skin tumours. In: Textbook of Dermatology. 5 ; Oxford; Blackwell Scientific publications; vol 2. 1992. p. 1497-502. |
|3.||Salehi Z, Mashayekhi F, Shahosseini F. Significance of eIF4E expression in skin squamous cell carcinoma. Cell Biol Int 2007;31:1400-4. |
|4.||Habif TP. Premalignant and Malignant Nonmelanoma Skin Tumors. In: Clinical Dermatology. 4 ; Elsevier publications; vol 4. 2007. p. 744-7. |
|5.||Toyoda H, Ido M, Nakanishi K, Nakano T, Kamiya H, Matsumine A, et al. Multiple cutaneous squamous cell carcinomas in a patient with interferon gamma receptor 2 (IFN gamma R2) deficiency. J Med Genet 2010;47:631-4. |
|6.||Ducloux D, Carron PL, Racadot E, Rebibou JM, Vautrin CB, Hillier YS, et al. CD4 lymphocytopenia in long-term renal transplant recipients. Transplantation 1998;65:1270-2. |
|7.||Vélez CR, Maciá JA, Brufau C, Carapeto FJ. Cutaneous squamous cell carcinoma and human papilloma virus. Actas Dermo-Sifiliográficas 2007;98:583-93. |
|8.||Wang AR, O'Brien M, Ross R, Long T, Robinson-Bostom L. Epidermotropic metastasis from vulvar squamous cell carcinoma: A rare cutaneous manifestation. J Am Acad Dermatol 2010;63:1088-91. |
|9.||Natoli C, Ramazzotti V, Nappi O, Giacomini P, Palmeri S, Salvatore M, et al. Unknown primary tumors. Biochimica et biophysica Acta 2011;1816:13-24. |
|10.||Rowe DE, Carroll RJ, Day CL. Prognostic factors for local recurrence metastasis and survival rates in squamous cell carcinoma of the skin, ear, and lip: Implications for treatment modality selection. J Am Acad of Dermatol 1992;26:976-90. |
[Figure 1], [Figure 2]