On physical exam, the patient was moderately overweight. His abdomen had a scar and there were fibrotic changes in the right inguinal region over the biopsy site. There was a large mass in the left inguinal area. On genitourinary exam, the patient's penis was uncircumcised and there was a 1.2 × 1.5-cm sessile, solid erythematous lesion around the urethral meatus (Fig. 1). The remainder of the exam was unremarkable.

The patient underwent a partial penectomy and bilateral superficial inguinal, deep inguinal and pelvic lymph node dissections. There was significant lymphadenopathy in the left inguinal region involving skin, which required a complete resection of the overlying skin. An abdominal fasciocutaneous flap was used for the resulting left inguinal defect.

Pathological review demonstrated carcinoma in situ of the glans penis (Fig. 2 and Fig. 3). There was no evidence of an invasive component and resection margins were negative. Five lymph nodes were positive for metastatic squamous cell carcinoma: a left and a right superficial inguinal node, a left deep inguinal node, and a left and a right pelvic node (Fig. 4). The patient was diagnosed with T3 N3 penile carcinoma in situ.

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 Fidler¹⁴ modernized Paget's¹⁵ historic “seed and soil” hypothesis into 3 principles: