Penile carcinoma is an uncommon condition, accounting for less than 1% of all male cancers.1
Possible etiologies include human papilloma virus infection, phimosis, poor hygiene and cigarette smoking.2,3,4,5
Several precancerous penile lesions have been associated with invasive squamous cell carcinoma, including Queyrat's erythroplasia. This is a carcinoma in situ of the glans penis, first described by Queyrat in 1911 as a red, velvety, slightly-raised lesion that is sometimes ulcerated and papillary.6
Metastasis from penile carcinoma in situ is extremely rare, as there have only been 2 other reported cases.7,8
Avrach and Christensen described an aggressive case of penile carcinoma in situ.7
The patient underwent circumcision and inguinal lymph node dissections that later revealed cancerous tissue.7
Metastasis to lumbar paravertebral lymph nodes, liver and lumbar vertebrae were later discovered post mortem.7
Eng and colleagues reported another case of a similar lesion with metastasis to the inguinal and para-aortic lymph nodes.8
The patient was initially treated with circumcision and topical 5-fluorouracil until metastatic disease was discovered several years later, for which he underwent systemic chemotherapy and an inguinal lymph node dissection.8
The detection of metastatic disease from carcinoma in situ is therefore often incidental or delayed.
Several other factors are responsible for treatment delays and diagnostic challenges observed in penile cancer. Penile lesions are often poorly characterized, morphologically, making it difficult to differentiate between benign and atypical, and low- and high-grade lesions.2,9
Further, the natural progression of carcinoma in situ to invasive squamous cell carcinoma remains controversial.2
Graham and Helwig reported the potential for malignant invasion of Queyrat's erythroplasia as 10% based on 100 cases, with only 2 progressing to malignant disease.10
Patient factors are also largely responsible for postponed treatment. Compared with patients with other cancer types, penile cancer patients have been shown to defer medical care, possibly owing to embarrassment, fear or personal neglect.11
In the presenting case, the penile lesion and inguinal masses developed over several years before the patient sought medical attention.
There have been few reports of other noninvasive carcinomas with metastasis, and there have been few theories to explain this unusual occurrence. Rosen reported 8 cases of breast ductal and (or) lobular carcinoma in situ with axillary lymph node involvement.12
He postulated that obscure foci of invasion may have been missed through random tissue sampling despite vigorous histological analysis. Further, Ozzello and Sampitak demonstrated invasion by electron microscopy of ultrathin tissue sections that appeared only as carcinoma in situ on light microscopy.13
They concluded that light optic analysis alone may be limited in detecting early invasive disease. Our patient's cancer, however, was longstanding so that we would expect to identify invasion on standard histological exam. Sampling error was also negligible since the lesion was small and had negative resection margins. Therefore, there are likely other unidentified possibilities to account for metastasis without evidence of invasion.
There has been significant research into the “metastatic cascade,” or the progression of a primary tumour to distant organs.14
historic “seed and soil” hypothesis into 3 principles:
- Neoplasms are composed of a biologically heterogeneous population, both genotypically and phenotypically.
- Metastasis is a selective process for tumour cells that can successfully migrate to distant sites and proliferate.
- Metastasis occurs preferentially in homeostatic environments that support the multiple interactions between the “seed” (tumour cell) and “soil” (organ).
Fidler's final principle may best explain the phenomenon observed in our patient. One hypothesis is that at a point in time of the primary tumour's natural history, tumour cells may have invaded the dermis, migrated and successfully proliferated in the lymph nodes with preferential host factors. The metastatic deposits then progressed and lead to further metastases rather than there being any further persistent findings of local progression and metastases from the primary tumour. The elucidation of such interactions, or “cross talk,” is ongoing and has the potential to revolutionize future cancer therapy.14
Our case highlights the possible tumour–host interactions necessary in the tumour and host microenvironment for tumour metastases without signs of persistent local tumour progression.