Eccrine porocarcinoma (EPC), or malignant eccrine poroma, is a rare skin malignancy that develops from the intraepidermal ductal portion of the eccrine sweat glands [1]. It has been estimated to account for between 0.005% and 0.01% of cutaneous tumors [1],[2]. Eccrine porocarcinoma was first described in 1963 by Pinkus and Mehregan and termed epidermotropic eccrine carcinoma [3].

Eccrine porocarcinoma usually arises in elderly patients (typically in the sixth and seventh decades of life), affects men and women equally, and typically arises the extremities [3],[4]. Often, elderly patients do not seek medical treatment immediately for the condition [4],[5]. Eccrine porocarcinoma has potential to be locally aggressive and spread to both regional lymph nodes and distant organs [6]. The typical presentation is as a nodule associated with warty epidermal changes with or without ulceration [7].

The treatment of EPC is constantly evolving [8]. The first step is to take a surgical resection [9]; however, beyond that there is no definitive conclusion whether radiotherapy or chemotherapy is preferred for sweat gland carcinomas [10]. A variety of chemotherapeutic approaches have been used with varying degrees of responsiveness; however, there is little evidence to support an optimal chemotherapy regimen [11],[12]. Metastatic EPC has demonstrated resistance to many cytotoxic agents [13],[14]. Some combination chemotherapy regimens have yielded short remission times; though, they often produce severe adverse effects [15].

Eccrine porocarcinoma is rare and metastatic presentation is even rarer. The purpose of this case report is to discuss a clinically challenging presentation of EPC and the imaging abnormalities associated with metastatic lesions.

A 62-year-old man presented with a history of a longstanding skin lesion on his distal right forearm. The patient reported the lesion persisting for at least 20 years; however, it started enlarging and becoming inflamed in the six months preceding his office visit. The patient described the lesion as originally “spongy” until it began to change in size and become tender. He had initially presented to his primary care physician who suspected an infected sebaceous cyst and subsequently attempted incision and drainage. During the attempted incision and drainage, a mass was noted, and punch biopsy was performed (Figure 1).

The biopsy specimen demonstrated extensively ulcerated, highly infiltrative carcinoma extending throughout the dermis into the subcutis involving the deep margin (Figure 2A and Figure 2B). The tumor cells were positive for cytokeratin 5, cytokeratin 7, p63, and p40 (Figure 2C). They showed areas of ductular differentiation. They were negative for cytokeratin 20 and TTF-1. In a subsequent analysis, the biopsy specimen was found to be negative for estrogen, progesterone, and HER2. The immunostains showed positive EMA, focal positive S100, negative CEA, and negative Melan A (Figure 2D and Figure 2E). Lymphovascular invasion was found to be present (Figure 2F).

After the biopsy results were obtained, a PET scan was ordered that demonstrated additional lesions (Figure 3A). The lymph nodes in the neck, mesenteric, retroperitoneal, and inguinal lymph nodes appeared to be clear and were neither enlarged nor hypermetabolic. Within the chest, hypermetabolic nodularity along the left hemidiaphragm was noted. Additionally, a mass was noted in the upper anterior thigh with a maximum standardized uptake value (SUV) of 17 (Figure 3B and Figure 3C)—as well as a satellite intramuscular lesion laterally with a maximum SUV of 9. There was also a hypermetabolic intramuscular lesion posterior to the left scapula (Figure 3D and Figure 3E). These results were overall consistent with metastatic disease involving the lungs, left hemidiaphragm, and intramuscular lesions in the left back and left thigh. Additionally, a lytic bone lesion was noted on the proximal left femur.

The patient was initiated on a chemotherapy treatment plan consisting of gemcitabine and protein-bound paclitaxel.

An MRI was performed six months later. This demonstrated a large necrotic mass in the vastus intermedius muscle with peripheral and thick septal enhancement on postcontrast sequence with a centrally necrotic component. A similar smaller necrotic mass was noted in the vastus lateralis muscle. On postcontrast axial sequence, multiple additional smaller enhancing lesions were seen in the vastus lateralis muscle. These multiple necrotic intramuscular lesions were suggestive of an increased degree of neoplastic involvement from the patient’s scan six months prior. Additionally, diffuse intramuscular edema and hyperemia in the muscles of the anterior thigh were noted that could represent nonspecific myositis or changes of acute or subacute denervation.

A repeat PET scan was also performed that demonstrated the previously described lesions had a significantly decreased tracer uptake, which was suggestive of response to therapy. The lesion in the left thigh had enlarged, but it was characteristic of fluid density without metabolic activity. This scan was valuable in that it helped clarify the MRI findings. In isolation, the MRI results may be misleading as they suggest progression; however, that progression could now be more accurately characterized as necrosis—as the PET showed decreased metabolic activity. Together, these findings highlight the relative usefulness of PET in staging with imaging studies.

The original chemotherapeutic plan was ceased after seven months as the patient reported negative effects including nausea, anorexia, and weight loss. The patient was started on sunitinib as an alternative chemotherapeutic agent.

Eccrine porocarcinoma is a rare primary malignant adnexal tumor of the skin [3]. There are four primary adnexal structures of the skin from which adnexal tumors can arise: the hair follicle, sebaceous, eccrine, and apocrine glands. Eccrine porocarcinoma arises from the eccrine sweat glands, which open directly onto the surface of the skin and are widely distributed [3],[6].

Our patient presentation of an elderly adult having a skin lesion for many years that has recently begun to change is a typical presentation of EPC. In terms of clinical diagnosis, eccrine gland carcinomas have no distinctive clinical features—making diagnosis by gross appearance effectively impossible [6],[16]. As in the case of our patient, histology is typically necessary for accurate diagnosis [17].

The classic histological findings are acanthotic epithelial proliferation containing clear cell nests with radial extension of polygonal nuclei, eosinophilic cytoplasm, and ductal structures with intraepidermal atypia [1],[18]. The duct differentiation varies from intracytoplasmic lumina to mature ducts with eosinophilic cuticles [19]. The cells of excretory coil of eccrine sweat glands are typically positive for the expression of low molecular weight keratin, EMA, CEA, and S100 protein in the basal layer [20]. Ki-67 and p53 may be used to differentiate benign from malignant lesions [20]. Some eccrine carcinomas are positive to estrogen and progesterone receptors, which has clinical implications for potential hormonal therapy [20].

The differential diagnosis of EPC is vast and a range of pathologies from basal cell carcinoma to metastatic adenocarcinoma need to be considered [11]. The differential should include eccrine poroma, squamous cell carcinoma, malignant melanoma, and occult visceral neoplasms [2],[21]. The lesions of EPC are verrucous plaques or polypoid protrusions that mimic squamous cell carcinoma or Bowen’s disease [22]. Both clonal seborrheic keratosis and Bowen’s disease are negative for CEA, CK 7, and S100, which are often positive in EPC [23]. Melanoma in situ can be ruled out by negativity for Melan-A and HMB-45 [23]. The metastatic deposits from visceral and breast adenocarcinoma are microscopically indistinguishable from eccrine carcinoma and thus should be considered before diagnosing the lesions as metastatic presentation of sweat gland carcinoma [6].

Porocarcinomas present with two models of growth: horizontal and nodular [24]. There has been disagreement in the literature whether EPC can be described as aggressive with a high rate of recurrence and metastasis [25]. A large case series by Robson et al. (69 EPC cases) found metastasis and recurrence rates of less than 20% [19],[25], suggesting that metastasis and recurrence are exceptions—rather than the norm. In metastatic presentation, nodal involvement is the most frequent form, with cutaneous metastasis being more rare [7]. Pedunculated tumors appear to be less aggressive and less likely to recur than tumors that present with ulceration and multinodularity [26]. Other previously described prognostic factors include depth of invasion, number of mitoses, and growth patterns of neoplastic margin [25]. The mortality among patients with EPC with nodal metastasis can be as high as 67% [27].

There is consensus that the initial treatment for EPC is typically total surgical excision [28]. Local excision with broad margins has traditionally been considered the standard of care; however, Mohs micrographic surgery (MMS) has gained prominence [9],[28]. The routine dissection of regional lymph nodes is, however, controversial—though lymphadenectomy may be indicated for patients with nodes that are clinically enlarged [15],[29]. In chemotherapeutic treatment, the agents such as methotrexate, cisplatin, doxorubicin, bleomycin, isotretinoin, and interferon alpha have been used with partial or little response [30].

For our patient, the lymph nodes were clear on computed tomography (CT) scan. The presenting lesion on his arm was resected, and chemotherapy was undertaken for the metastatic lesions using combination therapy consisting of gemcitabine and protein-bound paclitaxel. While this therapy demonstrated initially promising results, the patient’s reporting of unbearable side effects made the switch to sunitinib necessary.

Eccrine porocarcinoma is a rare skin malignancy that can be difficult to identify initially—with biopsy and immunohistology being key diagnostic tools. Eccrine porocarcinoma should be considered in the diagnosis of cutaneous malignant tumor.