History

Percivall Pott (1713–1788) 200th Anniversary of First Report of Occupation-Induced Cancer of Scrotum in Chimney Sweepers (1775)☆

Vulvar, penile, and scrotal neoplasms are (very) rare diseases. They have a similar embryological background and for this reason they develop similar diseases. We can find in each of these entities a human papillomavirus (HPV)-driven and a non-HPV-related pathway to cancer. In HPV-related tumors, HPV16 is the most common HPV type, but there are rare cases related to HPV6. Non-HPV-related tumors are caused by chronic inflammation on the basis of dermatoses like lichen sclerosus of differentiated vulvar intraepithelial neoplasia. A history of cervical precancer increases the risk for other HPV-related neoplasms. Treatment of choice for both, the invasive and preinvasive disease is surgery. Imiquimod is an alternative in vulvar precancer but every measure has to be taken to avoid delayed diagnosis of invasive cancer. HPV vaccination has the potential to prevent these HPV-related neoplasms of the female and male genital tract.

Scrotal cancer is the first described occupational cancer. The frequency of occupation-related scrotal cancer is very rare because of better hygiene and protective clothing. Human papilloma viruses (oncogenic types 16 and 18) were reported as the causative agents in the pathogenesis of scrotal cancers. E5, E6, and E7 proteins, expressed by human papilloma virus type 16, affect the cell cycle at the G1 checkpoint. TP53, p16^INK4A, and p15^INK4B were reported as the transcription factors that regulate the cell cycle on the same pathway. Here, the mutation pattern of TP53, p16^INK4A, and p15^INK4B genes and the homo/hemizygous deletion patterns of p16^INK4A/p15^INK4B genes are presented in four scrotal carcinoma cases. The results were correlated with the findings of oncogenic human papilloma viruses (types 16 and 18) in this panel. In two of four case, human papilloma virus type 16 was observed. Homozygous deletion in p16^INK4A/p15^INK4B genes and a codon 259 missense point mutation (GAC→TAC; Asp→Tyr) in the TP53 gene were observed in one human papilloma positive scrotal carcinoma case. The homozygous deletion in p16^INK4A/p15^INK4B genes was observed in another human papilloma positive scrotal carcinoma case. The cumulation of TP53 mutations and p16^INK4A/p15^INK4B homozygous deletions in human papilloma virus type 16 positive scrotal carcinoma cases indicate that the alterations of TP53, p16^INK4A, and p15^INK4B genes have an important role in the progression of scrotal cancers, as well as other factors. The survival rate for the two human papilloma virus type 16 positive patients who had a TP53 mutation or p16^INK4A/p15^INK4B homozygous deletion or both was lower than that for the human papilloma virus type 16 negative cases who had no TP53, p16^INK4A, and p15^INK4B mutation. The molecular alteration of TP53, p16^INK4A, and p15^INK4B genes may be useful as a prognostic marker in scrotal cancer.

Squamous cell carcinoma of the scrotum was diagnosed in 14 patients from 1945 to 1990. Patient age at diagnosis ranged from 40 to 73 years, with the mean age of 62 years. The most common presentation was a solitary skin lesion but inguinal adenopathy was noted in 5 patients (36%). The mean delay to diagnosis for all patients was 22 months, with a range of 2 months to 10 years. Predisposing factors included psoriasis treated with coal tar or arsenic, human papillomavirus infection and multiple cutaneous epitheliomas. The primary lesion was treated by local or wide local excision in all 14 patients. In addition, 4 patients underwent inguinal lymphadenectomy and 3 underwent radiotherapy to the pelvic and inguinal lymph nodes. Mean followup for all patients was 6 years. However, 11 patients were disease-free with a mean followup of 7 years. Improved prognosis was noted in patients with locally confined disease or carcinoma in situ only. There was no correlation between grade of tumor and survival. All patients with stages A1 and B disease treated with wide local excision and/or inguinal lymphadenectomy have done well on followup. Radiotherapy does not appear to impact on survival for patients with high stage disease.

Carbon black is frequently confused with soot. In order to clarify the distinction between these materials, we have examined 6 carbon blacks and 18 samples of soot. Carbon black is composed of turbostratic colloidal aggregates which we call aciniform carbon (AC). Chimney soots from domestic wood or coal fires contain very little AC, while in diesel soots the solid particulates are essentially all AC. All soots examined contain much more extractable organic material and/or ash than does carbon black. Ames Salmonella assays were carried out on solvent extracts. The results were calculated as net revertants per mg of the original soot or carbon black. On this basis, the majority of the soot extracts assayed were at a much higher level of mutagenicity than any of the carbon black extracts. For several reasons, even greater differences in mutagen availability would be expected if the unextracted materials were compared in vivo.

Twelve patients with carcinoma of the scrotum were evaluated: 9 with squamous carcinoma and 3 with basal cell carcinoma. The presenting complaint was a visible skin lesion; the interval between awareness of this lesion and diagnosis averaged 3.3 years. Three of the 12 patients were black, although this disease previously has been considered rare in blacks. No occupation predominated among the patients in this series, and scrotal carcinoma today may occur as a result of nonspecific factors such as poor hygiene and chronic irritation, rather than industrial exposure. Only 5 of 12 patients were disease free after treatment; 5 of the others died of squamous carcinoma, 1 died of a postoperative complication, and 1 was lost to follow-up. The most significant correlative with survival was stage at initial diagnosis, indicating the need for a high index of suspicion regarding lesions of the scrotum.