In-transit metastases from squamous cell carcinoma penis.

An in-transit metastasis is one that is located between the primary tumor and the closest lymph node region and results from tumor emboli getting trapped in the lymphatic channels. A 65-year-old male patient who had undergone partial amputation of the penis and bilateral inguinal lymph node resection for squamous cell carcinoma of the penis 4 months earlier developed multiple cutaneous metastatic lesions in the pubic region and scrotum. The case is reported for the uncommon presentation of in-transit metastases.

Introduction

Cutaneous metastases are of diagnostic importance as they may be the first manifestation of an undiscovered internal malignancy or the first indication of metastasis from a supposedly adequately treated malignancy.[1] As a rule, cutaneous metastases usually appear in the skin close to the primary tumor. Most regional metastases probably occur through the lymphatic system, while distant metastases are more likely to occur via the hematogenous route.[2]

In-transit metastases are cutaneous metastatic foci located between the tumor and the closest regional lymph nodes. A case of squamous cell carcinoma (SCC) of the penis with numerous in-transit metastases in the pubic region and scrotum is reported for its rarity.

Case Report

In May 2010, a 65-year-old male patient presented at our hospital with complaints of numerous papules and nodules in the pubic and suprapubic region and the scrotum. According to him the lesions had been present for the last 4 months. In October 2009, he had undergone partial amputation of the penis at a tertiary care hospital for an ulceroproliferative growth involving the glans penis, which was histologically proven to be a moderately differentiated SCC.

A fine needle aspiration cytology (FNAC) of the left inguinal nodes at the same teritiary care hospital where patient underwent surgery, revealed well-differentiated metastatic SCC on the left side and reactive lymphoid hyperplasia on the right side. Bilateral block resection of inguinal lymph nodes, wth skin grafting from a donor site from the thigh, was performed. However, 4 months later he developed edema of both lower limbs, scrotum, and the suprapubic region. He also developed multiple painless papules and nodules in the above areas, with some of the lesions discharging a clear fluid. A diagnosis of post-lymphadenectomy lymphangiectasia, was entertained at that time at the tertiary care hospital and the patient was treated conservatively and reassured.

He presented at our hospital in May, 2010, with multiple papules and nodules (some of them ulcerated) on the scrotum and the pubic and suprapubic regions. Local examination revealed edema of the scrotal skin and suprapubic region, a short stump of the amputated penis, postsurgical scars in both inguinal regions, and postinflammatory pigmentary changes – both hypo- and hyperpigmentation – at the donor site on the thigh [Figure 1]. There were multiple firm papules and nodules of about 2–3 mm in size, some of them ulcerated and discharging serous fluid, in the pubis, suprapubic region, and scrotum. A biopsy from one of the papules revealed a metastatic deposit. [Figure 2] Roentgenogram of the chest and ultrasonogram of the abdomen did not reveal any metastatic deposits. Other than anemia (with hemoglobin of 8.1 gm%), the routine hematologic and biochemical investigations did not reveal any abnormality.

Figure 1

Edema of the scrotal skin and suprapubic region, the short stump of the amputated penis, and postsurgical scars in both inguinal regions.

Figure 2

Islands of metastatic squamous cell carcinoma with a clear zone between the deposit and the epidermis. Overlying stratified squamous epithelium is normal (H and E; A ×200, B ×400)

A diagnosis of SCC with in- transit cutaneous metastasis was made and the patient was referred back to the tertiary hospital for further management. However, he was later lost to follow-up.

Discussion

Carcinomas arising from modified skin such as the glans penis and the vulva and from the oral mucosa have a rather high rate of metastasis unless they are recognized and adequately treated at an early stage.[3] Carcinomas arising in sun-damaged skin have a very low propensity to metastasize, the incidence being only about 0.5%.[4] The rate of metastases is higher in adenoid and mucin-producing SCC of the skin than in the common type.[3] However, in our patient, details about the histological type of the primary lesion were unavailable. Dissemination may take place via the lymphatics or the blood stream.[1]

In-transit metastases are cutaneous metastatic foci located between the tumor and the closest lymph node region. Analogous to in-transit metastasis found in melanoma, these represent metastatic spread along lymphatic vessels and/or nerves and their presence is an indicator of poor prognosis.

In the present case, in view of the innumerable papulonodules and the previous history of regional (i.e., inguinal) lymph node involvement as proved by FNAC study, lymphatic spread was probably the reason for these in transit metastases.

A case of penile cancer has been reported earlier where the patient presented with primary high-grade penile squamous carcinoma and secondary skin metastases, in addition to metastases to liver, lungs, and other organs.[5] However, in our patient there was no clinical or radiological evidence of involvement of other organs.

Overall, in-transit metastases occur most frequently from SCC risk stratified as high-risk lesions; however, all SCC that occur in immunosuppressed patients have the potential for distant spread. Ninety percent of metastatic SCC occurs within 3 years of diagnosis of the primary tumor. In our patient, however, the metastasis occurred within a much shorter period of 4 months. It is possible that the tumor emboli were already lodged in the lymphatic channels at the time the inguinal node resection was undertaken and hence this early recurrence.

Clinically, in-transit metastasis are nondescript, subtle, waxy, gray-white or flesh-colored papules of about 2–6 mm diameter and are not contiguous with the primary lesion.[6] This was the picture in our patient, who had multiple such nondescript papules. An erroneous diagnosis of postsurgical sequelae and lymphangiectasia is often made. Such a diagnosis was entertained in the present case also at the tertiary care hospital 3 months prior to his visit to our hospital.

In a review of 21 cases with in-transit metastases, Carucci et al. reported that patients presented most commonly with discrete dermal papules distinct from, but in the vicinity of, the primary tumor site.[6] In their series, histologic differentiation was variable. These findings are similar to the features in our patient.

Local control of in-transit metastasis should be achieved with Mohs surgical technique or some other surgical method, where the surgical margins are rigorously evaluated for residual tumor, perineural extension, or intravascular invasion (e.g., excision with intraoperative frozen section control or excision with postoperative margin assessment). Postoperative radiation should be strongly considered. The radiation field often involves the primary tumor site, the in-transit metastatic site, and the draining lymph node basin. Our patient was referred for further treatment to the same tertiary care hospital where he had earlier undergone surgery for his SCC penis, but he was lost to follow-up.

This case is presented because of the uncommon presentation of ‘in-transit’ metastases after the primary tumor and the regional lymph nodes were resected.