Year: 2018 I Volume: 1 I Issue: 1 I Page: 12-15
Spectrum of cutaneous manifestations in patients with internal malignancies: A clinico-epidemiological study
Naushin Aara 1, Mehta R. D.1, Bumb R. A.1, Ghiya B. C.1, Soni P.1, Kumar H.S.2
1 Department of dermatology, venereology and leprosy, Sardar Patel Medical College, Bikaner, Rajasthan, India
2Department of radiotherapy, regional cancer research and treatment center, Sardar Patel Medical College, Bikaner, Rajasthan, India
Dr. Naushin Aara,
320/B Udyog Nagar, Jhotwara,
Jaipur, Rajasthan- 302012. India
How to cite this article:
Naushin Aara, Mehta RD, Bumb RA, Ghiya BC, Soni P, Kumar HS. Spectrum of cutaneous manifestations in patients with internal malignancies: a clinico-epidemiological study. JDA Indian Journal of Clinical Dermatology 2018;1: 12-15.
Background: The skin can provide important clues to systemic disease and internal malignancies; recognition of these clues facilitates both early diagnosis and prompt treatment of internal malignancy. This study was undertaken with objectives of knowing the spectrum of cutaneous manifestation in patients suffering from various internal malignancies.
Methods: A total of 1000 patients with internal malignancies were screened in this study. Relevant investigations for diagnosis of internal malignancy and dermatological disorders were carried out.
Result: Skin changes were present in 644 cases (64.4%). Majority of the patients were in the age group of 40-60 years. In seven patients dermatological changes were the presenting sign of internal malignancy. Specific skin lesions were found in 16 cases (1.6%) out of which cutaneous metastases was present in 11 patients (1.1%), lymphoma cutis in 3 (0.3%), carcinoma en cuirasse and inflammatory carcinoma of breast in one patient each. Four hundred and eighty six patients had dermatological conditions under nonspecific category and 222 patients had therapy related cutaneous adversities. Few patients had more than one skin changes. Most common nonspecific skin lesions were paraneoplastic dermatoses (21.8%), fungal infection (9.0%), xerosis (6.6%) and viral infections (6.9%). Radiation dermatitis was the most common therapy related changes seen in 12.8% patients.
Conclusion: A patient of internal malignancy can present with specific or nonspecific skin changes and can be a presenting sign of internal malignancy. Elderly patients with unusual dermatological presentation and unresponsive to conventional therapy must be thoroughly investigated for internal malignancy.
Key words: cutaneous manifestation of malignancies, cutaneous metastasis
Skin being the largest and most visible organ of the body, may provide a useful indicator for systemic diseases including malignancies. Internal malignancies may affect the skin both directly and indirectly. Direct involvement implies the presence of tumor cells within the skin which may occur either by local extension or by tumor metastasis through hematogenous and lymphatic routes.1 Indirect involvement by internal malignancies includes, genodermatoses, paraneoplastic disorders, certain indirect cutaneous markers and adverse effects of either chemotherapy or radiotherapy.2 These cutaneous markers of malignancy may occur before, at the same time as or after the diagnosis of the tumor.3,4 The timely diagnosis of these conditions is important as paraneoplastic dermatoses often cause considerable morbidity and in some instances may lead to detection of an otherwise clinically occult tumor at an early and treatable stage. To best of our knowledge, previous reports regarding incidence of cutaneous manifestations of internal malignancies are limited and include mainly case series, reviews and retrospective studies. To know the overall frequency and clinical profile of skin diseases associated with internal malignancies we conducted a study among the patients attending outpatient department of dermatology and regional cancer research and treatment center in Bikaner, north India.
Materials and methods:
One thousand patients of internal malignancies of various duration involving different organs, with or without treatment, were included in present study. Only those cases confirmed to be having internal malignancy were included. A detailed epidemiological data was collected; also history regarding malignancy and dermatological complaints, details about cutaneous changes, systemic examination, relevant investigations and treatment details of internal malignancy were recorded in a printed proforma. Skin biopsies for histopathology, scrapings for fungal infections and Gram staining, culture and sensitivity of purulent material were done whenever required. Diagnosis of malignancies was done by oncologist on the basis of clinical examination and relevant investigations including cytological, histopathological, biochemical, hormonal and radiological examination for respective malignancies. Clinical photographs of skin manifestations were also taken in patients having specific skin lesion.
Out of 1000 patients studied, 477 (47.7%) were males and 523 (52.3%) were females. Majority of the patients were in the age group of 41-50 years (322; 32.2% patients) followed by 259 (25.9%) patients in 51-60 years age group. Only 4 patients were below 10 years (Fig. 1).
|Figure 1. Age distribution of patients|
Overall, most common malignancy was carcinoma breast (20.4%) followed by carcinoma cervix (19.6%), lymphoma (12.8%), leukaemia (6.7%), carcinoma oral cavity (6.6%), broncho-pulmonary carcinoma (6.4%) and carcinoma ovary (4.5%). The other malignancies encountered were carcinoma oesophagus, laryngeal carcinoma, gastro-intestinal malignancies, pharyngeal carcinomas, hepato-biliary carcinoma, carcinoma prostate, secondary metastasis with unknown primary, multiple myeloma, carcinoma of testes, urinary bladder, vagina, endometrium, brain and thyroid in decreasing order of frequency.
The malignancies observed in males were lymphomas in 125 (12.5%), broncho-pulmonary carcinomas in 62 (6.2%) and oral cavity malignancies in 56 (5.6%) cases, while in females there was carcinoma breast in 204 (20.4%), carcinoma cervix in 196 (19.6%) and carcinoma ovary in 45 (4.5%) cases.
Skin lesions were found in 644 (64.4%) patients out of 1000 cases studied. Out of 644 patients, in only seven (1.08%) patients cutaneous diseases were diagnosed before diagnosis of internal malignancy.
A total of 51 different types of dermatological manifestations were seen. We observed three categories of cutaneous changes in patients of internal malignancies; 486 patients had nonspecific changes whereas 222 cases were found to have treatment related skin changes and only 16 patients had specific dermatological lesions pertaining to malignancies. Thirty four patients suffered from more than one cutaneous finding.
Cutaneous metastases was the commonest specific lesion in 11(1.1%) patients followed by lymphoma cutis in 03 (0.3%), carcinoma en-cuirasse and inflammatory carcinoma of breast in one patient each (Fig. 2-5).
|Figure 2: Cutaneous metastases in a breast carcinoma patient|
|Figure 3a: Lymphoma cutis in a patient with non-Hodgkin’s lymphoma|
|Figure 3b: Lymphoma cutis in a patient with non-Hodgkin’s lymphoma|
|Figure 4: Carcinoma encuirrase in a breast carcinoma patient|
|Figure 5: Inflammatory carcinoma of breast|
Out of 11 patients of cutaneous metastases, 8 patients showed contiguous metastases from underlying carcinoma while 3 patients had non-contiguous metastases occurring at a distant site. Most common site of cutaneous metastases was anterior chest wall in 4 cases and most common type of lesion was nodules in 7 cases. There were 3 cases of metastases, manifesting as presenting sign of internal malignancy (Table 1).
|Table 1. Distribution of cutaneous metastases|
Most common non specific cutaneous lesions were paraneoplastic disorders affecting 218 (21.8%) patients followed by infections and infestations in 207 (20.7%) patients (Table 2).
|Table2. Distribution of nonspecific skin changes|
Among them most common skin changes were fungal infections in 90 (9.0%), viral infections in 69 (6.9 %), xerosis in 66 (6.6%) and pruritus in 39 (3.9%) cases. Other non-specific skin lesions included intertrigo, seborrheic dermatitis, lichenoid eruptions, perianal dermatitis, photodermatitis, eczematous eruption around nipple areola complex, pityriasis rosea, aphthous ulcers, icterus, koilonychias, lymphangiactasis, psoriasiform dermatitis and hiderdinitis suppurativa.
Therapy related skin changes were encountered in a total of 222 (22.2%) cases. Radiation dermatitis was the most common in 12.8% patient (Fig. 6), alopecia in 74 (7.4%), flagellate pigmentation was found in 4 cases (Fig. 7) and others.
|Figure 6: Radiation dermatitis in a case of carcinoma breast after mastectomy|
|Figure 7: Flagellate pigmentation in a patient of carcinoma ovary treated with Bleomycin|
Skin is the window to systemic diseases and malignancies, as it is readily visible. Our study revealed a high prevalence (64.4%) of dermatological manifestations in patients suffering from internal malignancies which was greater than the observations of previous studies by Rajagopal et al5 (27.3%), Kilic et al6 (45.14%) and Ayyamperumal et al7 (6.93%). In present study females were more commonly affected than males in contrast to previous studies.5,6,7,8
Skin is an infrequent site for metastases and the rates of metastases from internal malignant diseases to the skin varies between 0.7% and 9%.9,10 In present study incidence of cutaneous metastasis was 1.1% which is consistent with findings of Kilic et al.6 Cutaneous metastases commonly present as single or multiple nodules, which are always firm and rubbery to stony hard in consistency, often fixed to underlying tissue.10 In present study, 3 out of 8 cases with contiguous metastases and 1 out of 3 cases of noncontiguous metastases had multiple lesions. Beside the nodules, we also encountered plaques, papules and ulcers. Anterior chest wall was the most common site for metastases as reported in earlier studies conducted by Rajagopal et al,5 Ayyamperumal et al,7 Benmously et al,11 Gul et al12 and Kanitakis.13 The common primary malignancies reported with cutaneous metastases are lung cancers in males, and breast cancer in females.11,14,15 In our study carcinoma breast was found to be the commonest malignancy in females and Non-Hodgkin lymphoma in males.
Risk of infections is generally increased in internal malignancies due to an immunocompromised status which is caused either by chemotherapy or disease process itself.16 Most frequent non-specific skin lesions encountered in our study were fungal infections in 90 (9.0%) patients which is similar to study conducted by Kilic et al.6 Herpes zoster was present in 5.7% cases and found to be disseminated, nondermatomal and ulcerated in most of the cases. It has been reported to be most often seen in hematological malignancies like chronic lymphocytic leukemia and lymphomas,5,6,17 while present study revealed carcinoma breast to be the most common malignancy associated with herpes zoster.
Xerosis and nonspecific pruritus were found in 6.6% and 3.9% out of 1000 cases in our study. Among the malignant diseases, it was most often observed in leukemia and lymphomas. Goldman and Koh found pruritus in 35% of patients suffering from Hodgkin’s disease.18 In our study xerosis was most commonly associated with carcinoma breast (1.8%) and carcinoma cervix (1.6%) while pruritus was associated with carcinoma cervix (0.7%) and carcinoma breast (0.6%). Lymphoma was the third most common malignancy with four cases. This difference may be due to more prevalence of the carcinoma of breast and cervix cases in our study. Up to 50% of the patients with pruritus without any obvious dermatological cause also have an underlying systemic disease process including malignancies.19 Persistent pruritus not otherwise explained by an obvious dermatologic condition should prompt an investigation for underlying systemic cause.
Palmoplantar keratoderma (PPK) both acquired and familial forms are also related with malignancies.20, 21 We found acquired palmoplantar keratoderma in 6 patients, most commonly associated with hematological malignancy (0.4%) which was similar to study by Kilic et al.6 In one case palmoplantar keratoderma was presenting sign of carcinoma brain (astrocytoma). Kilic et al6 also reported diffuse hyperpigmentation in 0.28% patients with gastrointestinal carcinomas. In our study it was seen in hepato-cellular carcinoma, carcinoma lung and multiple myeloma with a prevalence of 0.3%.
In our study we encountered 27 (2.7%) cases of vascular disorders. These included erythema multiformae (0.8%), vasculitis (0.6%), purpura (0.4%), necrotizing ulcers (0.4%), flushing (0.2%), thrombophlebitis (0.2%) and acral gangrene (0.1%). In one case of vasculitis, Raynaud’s phenomenon was also positive and it was associated with non-Hodgkin’s Lymphoma (NHL). Cutaneous vasculitis is more likely to be associated with hematologic cancers.22 Flushing is most commonly associated with carcinoid syndrome of gastrointestinal and bronchial origin23 but in our study one case was associated with carcinoma of testis and other was the case of acute lymphocytic leukemia (ALL).
Radiation dermatitis was the most common treatment related change in 12.8% patients followed by alopecia in 7.4% patients. Drug induced urticaria were found in 16 (1.6%) patients which was higher than the findings of Kilic et al6 study (0.42%) and Rajagopal et al5 study (0.66%). The antigens originating from various foci from the tumor may be urticariogenic. Flagellate pigmentation was found in 4 (0.4%) patients due to bleomycin which was almost similar with Rajagopal et al study (0.3%).
In addition, our study showed some cutaneous manifestations which had very low incidence such as scabies, intertrigo, seborrheic dermatitis, lichenoid eruptions, perianal dermatitis, photodermatitis, eczematous eruption around nipple areola complex, pityriasis rosea, aphthous ulcers, icterus, koilonychia, paraneoplastic pemphigus, Bazex’ syndrome, lymphangaictasis and psoriasiform dermatitis.
We conclude that skin is an indicator of milieu interior. Skin manifestations might occur before, simultaneously or after the diagnosis of internal malignant disease. A patient presenting with dermatological manifestation with unusual presentation, long duration and resistant to treatment should be thoroughly investigated for internal malignancies.
In the study all types of malignancies could not be covered so some cutaneous findings could have been missed and also genodermatoses were not covered.
Conflicts of interest:
There are no conflicts of interest.
1. Schwartz RA. Cutaneous Metastatic disease. J Am Acad Dermatol 1995; 33: 161-82
2. Cox NH, Coulson IH. Systemic disease and the skin. In: Burns T, Breathnach S, Cox N, Griffiths C. eds. Rook’s Textbook of Dermatology. 8th edn. Wiley-Blackwell, 2010. P. 62.14.
3. Thiers BH, Sahn RE, Callen JP. Cutaneous Manifestations of Internal Malignancy. CA Cancer J Clin 2009; 59: 73-98.
4. Legbo JN, Legbo JF. Cutaneous manifestations of malignant disease: a review. Niger J Med 2007; 16(1): 18-24.
5. Rajagopal R, Arora PN, Ramasastry CV, Kar PK. Skin changes in Internal malignancy. Indian J Dermatol Venereol Leprol 2004; 70: 221-5.
6. Kiliç A, Gül U, Soylu S. Skin findings in internal malignant diseases. Int J Dermatol 2007; 46: 1055-60.
7. Ayyamperumal A, Tharini GK, Vidya Ravindran, Praveen B. Cutaneous manifestations of internal malignancy. Indian Journal of Dermatology 2012; 57(4): 260-4.
8. Ortega-Loayza AG, Ramos W, Gutierrez EL, Paz PC, Bobbio L, Galarza C. Cutaneous manifestations of internal malignancies in a tertiary health care hospital of a developing country. An Bras Dermatol. 2010; 85: 736-42.
9. Lookingbill DP, Spangler N, Sexton FM. Skin involvement as the presenting sign of internal carcinoma. A retrospective study of 7316 cancer patients. J Am Acad Dermatol 1990; 22: 19-26.
10. Lookingbill DP, Spangler N, Helm KF. Cutaneous metastases in patients with metastatic carcinomas: a retrospective study of 4020 patients. J Am Acad Dermatol 1993; 29: 228-36.
11. Benmously R, Souissi A, Badri T, Ben Jannet S, Marrak H, Mokhtar I, et al. Cutaneous metastases from internal cancers. Acta Dermatovenerol Alp Panonica Adriat. 2008; 17(4): 167-70.
12. Gul U, Kilic A, Gonul M, Kulcu Cakmak S, Erinckan C. Spectrum of cutaneous metastases in 1287 cases of internal malignancies: a study from Turkey. Acta Derm Venereol 2007; 87 (2): 160-2.
13. Kanitakis J. Cutaneous metastases of internal cancers. Presse Med 1993; 22(13): 631-6.
14. Tharakaram S. Metastases to the skin. Int J Dermatol.1988; 27: 240-2.
15. Brownstein MH, Helwig EB. Pattern of cutaneous metastasis. Arch Dermatol 1972; 105: 862-8.
16. Mclean DI, Haynes HA. Cutaneous manifestations of internal malignant disease. In: Fitzpatrick TB, Freedberg IM, Eisen AZ, Wolff K, Austen KF, editors. Dermatology in general medicine. New York: McGraw Hill; 1999. p. 2106–20.
17. Fogo A, du Vivier, A. Cutaneous manifestation of hematological malignancy. Clinical Medicine 2009; 9 (4): 366-70.
18. Goldman BD, Koh HK. Pruritus and malignancy. In: Bernhard JD editor. Itch-Mechanisms and Management of Pruritus. New York: McGraw – Hill; 1994: 299-319.
19. Zirwas MJ, Seraly MP. Pruritus of unknown origin: a reterospective study. J Am Acad Dermatol 2001: 45: 892-6.
20. Patel S, Zirwas M, English JC 3rd. Acquired palmoplantar keratodeerma. Am J Clin Dermatol 2007; 8(1): 1-11.
21. Moore RL, Devere TS. Epidermal manifestations of internal malignancy. Dermatol Clinics 2008; 26: 17-29.
22. Kurzrock R, Cohen PR. Vasculitis and cancer. Clin Dermatol 1993; 11(1): 175-87.
23. Modlin IM, Sandor A. An analysis of 8305 cases of carcinoid tumors. Cancer 1997; 79: 13-29.