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\begin{document}

\title{Porocarcinoma of the Left Arm: A Report of a Rare Skin Cancer Case and
Literature Review}



\author[1]{Carlo Signorelli}%
\author[2]{Luca Zanella-Cavallero}%
\author[3]{Valentina Ranucci}%
\author[2]{Antonio Pellicciotti}%
\author[1]{Enzo Maria Ruggeri}%
\affil[1]{Medical Oncology Unit, Belcolle Hospital, ASL Viterbo}%
\affil[2]{General Surgery, Tarquinia Hospital, ASL Viterbo}%
\affil[3]{Pathology Unit, Belcolle Hospital, ASL Viterbo}%


\vspace{-1em}



  
  \date{May 05, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Porocarcinoma is a rare type of skin cancer that develops from the
intraepidermal ductal part of eccrine sweat glands. It can arise de novo
or from poroma ground with high potential for locoregional metastatic
spread, morbidity, and mortality. It mostly occurs in elderly patients.%
\end{abstract}%



\sloppy


\textbf{Introduction}

Porocarcinoma (PC), first described in 1963 by Pinkus and Mehregan, is a
rare malignant skin tumor originating from the intraepidermal ductal
portion of the sweat glands. It accounts for an estimated
0.005\%--0.01\% of all cutaneous carcinomas {[}1{]}.

The pathogenesis is not fully understood; it was proposed that \emph{de
novo} PC may develop from a pre-existing poroma through various
triggers, including exposure to chemical agents, ultraviolet light,
trauma, burning or radiotherapy, immunosuppressive drugs, especially
after organ transplantation, and acquired immunodeficiency syndrome. It
mainly occurs in adults aged between 21 to 90 years, according to
different studies. PC occurs in both sexes equally {[}2-5{]}.

Recent literature has reported that PC most commonly arises on the lower
limbs (33\%), head and neck (32\%), trunk (14.7\%), genitalia/buttocks
(11.2\%), and upper limbs (7.4\%). The location on the arms represents
only 4.8\% of PC common sites (only 14 cases have been registered at the
moment) {[}6-16{]}.

In this case report, we present a case of PC that gradually ulcerated
over about 10 months on the left arm of a 93-year-old male patient with
various comorbidities with a literature review on PC and its potential
therapy.

\textbf{Case Presentation}

A 93-year-old Caucasian male patient came to our observation after
undergoing resection of a grayish-yellow polypoid neoplasm with
irregular contours and 2.5-cm maximum diameter in the skin of the distal
third of the left arm approximately 8 months ago.

Originally, the neoplasm was mobile, with a brownish-red color, an
irregularly circular base, and a maximum diameter of less than one
centimeter, and asymptomatic (Fig. 1). Following rapid growth, the
patient underwent surgical excision of a skin and subcutis lozenge
measuring 5.5 \selectlanguage{ngerman}× 2.3 × 1.5 cm under local anesthesia with lidocaine.
Histological examination revealed a largely ulcerated and necrotic PC
infiltrating the papillary dermis and the first portion of the reticular
dermis (Fig. 2).

On clinical examination, the patient, transported in a wheelchair due to
a severe degenerative joint disease limiting walking, had a very poor
general condition, a ECOG (Eastern Cooperative Oncology Group) PS
(performance status) of 3, and declining edema without other skin
lesions or palpable superficial lymphadenopathy.

The histological picture and clinical history made it possible to
formulate the diagnosis of PC that probably arose on a pre-existing
poroma. Ultrasound of the abdomen and main lymph nodes and a chest X-ray
were normal, excluding metastases.

Considering the patient's age, poor general condition, comorbidities,
and absent distant metastasis, periodic checks in the dermatological
clinic were indicated. Written informed consent was obtained from the
patient for publication of this case report and accompanying images.

\textbf{Discussion}

PC is a rare, aggressive, and chemoresistant skin cancer arising from
one of the four primary adnexal structures of the skin: the hair
follicle and sebaceous, eccrine, and apocrine glands; more exactly, it
derives from terminal cells of the intraepithelial part of the eccrine
duct called the acrosyringium {[}4{]}.

This aggressive tumor can metastasize to local lymph nodes or distant
organs. Skin metastases may be found near the primary tumor. Other less
usual metastatic sites include lung, liver, breast, ovaries, bone,
bladder, and retroperitoneum.~ The most common locations affected by PC
are the lower extremities, head and neck, trunk, genitalia/buttocks, and
upper extremities {[}5{]}.

PCs located on the genitalia and buttocks have a higher propensity for
distant metastases compared to those arising in the head and neck area.
Metastatic disease is already present at diagnosis in up to 31\% of
cases, where the most common sites involved are regional lymph nodes
(60\%) and lungs (13\%). The related prognosis is poor, with 50\%-- 80\%
mortality and 9\% of overall survival rates of 10-years.

To date, only 15 cases occurring on the arms (including the current
case) have been documented in the literature {[}7-31{]}. Clinically, PC
presents as a slow-growing, red, dome-shaped skin nodule with a shiny
surface or as a wart-like plaque, papule, or polyp that is sometimes
painful and ulcerative. The lesion size can range from less than 1 cm to
up to 10 cm.

Due to its rarity, PC can mimic other skin conditions and could be
misdiagnosed as other cutaneous neoplasms, particularly as squamous cell
carcinoma. Differential diagnosis is mandatory in the presence of other
skin lesions, such as amelanotic melanoma, seborrheic keratosis,
pyogenic granuloma, Bowen's disease, verruca vulgaris, fibroma, or even
metastatic adenocarcinoma. Thus, diagnosis is often delayed, and optimal
management is lacking. Due to its aggressive nature, the prognosis for
local recurrence after standard-wide local excision is poor, with a
recurrence rate of 20\% {[}10{]}.

Histologically, PC can be recognized by lobules and cords of pleomorphic
basaloid cells with enlarged hyperchromatic nuclei and mitotic activity.
Two histopathological variants of PC exist: trabecular and
epidermotropic. The second one is more aggressive than the first and is
frequently associated with local recurrences and metastatic lesions
{[}6{]}.

The survival for patients with distant metastases is reported to be 5 to
24 months. Mortality is high, reaching 80\% in distant diseases and
65\%--67\% when lymph nodes are involved.~ Given its rare occurrence,
most of the literature has reported single clinical cases and a few case
series, and there are currently no uniform international guidelines for
these patients {[}7-31{]}.

There is no standard treatment for metastatic disease. Undoubtedly, the
treatment of choice is wide excision, which results in cure rates of
70\% to 80\%. Although good results have been reported with 3- to 5-mm
resection margins, surgical margins should range from 1 to 2 cm. When
the disease is inoperable or advanced, systemic treatment represents a
challenge. Mohs micrographic surgery may be a valid effective treatment
option for PC. The role of sentinel lymph node biopsy is not yet well
defined, although it could be useful for high-risk PC in cases with
signs of histological aggression or intralymphatic involvement {[}10{]}.

Treatment of distant metastatic PC is not yet well defined. Neither
chemotherapy nor radiotherapy has been clinically advantageous in
metastatic disease. In this regard, various therapeutic schemes have
been evaluated with many uncertain results. Among these, taxane-based
regimes have proven to be effective, with a response in 50\% of cases.
Paclitaxel plus cetuximab have been observed to provide an almost
complete morphological response and a complete metabolic response at all
locations of metastatic PC with strong epidermal growth factor receptor
(EGF-R) expression, except for persistent bone metastases, where,
however, metabolic activity was low due to the radiation therapy
{[}32{]}.

In the literature, we found other interesting case reports. Complete
remission was also seen with polychemotherapy with doxorubicin,
mitomycin C, vincristine, and 5-fluorouracil (5-FU), alternating with
cisplatin and bleomycin or hyperthermic perfusion with 5-FU and
melphalan. Other agents have been administered in combination, including
cisplatin and docetaxel, carboplatin and paclitaxel; doxorubicin,
mitomycin, vincristine, and 5-fluorouracil; anthracycline,
cyclophosphamide, vincristine, and bleomycin; isotretinoin and
interferon-alpha {[}33-35{]}. Other case series described using topical
5-FU and intraarterial docetaxel and docetaxel as a single agent.
Furthermore, long-term outcomes have been recently achieved with
pembrolizumab {[}36{]}.

Radiosensitivity of PC is suggested by some case reports. Adjuvant
radiotherapy is not yet standard of care, but it would be recommended in
high-risk situations, such as cases with positive surgical margins,
tumors larger than 5 cm, lymphovascular involvement, and tumors with
moderate to poorly differentiated grading {[}37{]}. Metastatic cervical
lymph nodes successfully treated with cyberknife radiosurgery have also
been mentioned {[}38{]}.

In conclusion, the best chance for cure is early diagnosis and surgery
because neither chemotherapy nor radiotherapy has shown some clinical
benefit in metastatic PC.



\textbf{Conclusions}

PC is rare and challenging to recognize skin cancer with a high risk of
recurrence and metastasis. Despite its rarity, eccrine PC is the most
common sweat gland. The differential diagnosis for every suspicious
cutaneous lesion is needed to prevent delays in treatment.

Our clinical case suggests that early identification and complete
excision offer the best chances of feasible recovery even in elderly
patients in poor general condition and with numerous comorbidities.

No treatment has been standardized yet. Surgery is the first and only
therapeutic option that could significantly affect patient outcomes.
Chemotherapy and radiotherapy have not shown clinical benefits in the
management of advanced PC.

Due to its rarity, further research, including case reports, is
necessary to improve the diagnosis and therapy of PC.

\textbf{Authors' contributions.}

Conceptualization: CS. Data Curation: CS. Investigation: CS EMR LZC VR
AP. Visualization: CS VR. Writing -- Original Draft Preparation: CS.
Writing -- Review \& Editing: CS EMR. All authors have read and approved
the final manuscript.

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\par\null

\par\null

\textbf{Figures}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

\textbf{Fig. 1} \textbf{Porocarcinoma of the left arm.}

Clinical appearance of the 2.5 cm of maximum diameter brownish-red color
polypoid neoformation with irregular contours and circular base arising
at the skin level of the distal third of the left arm.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/Figures-2A,-2B,-2C.tiff}

\end{center}
\end{figure}

\textbf{Fig. 2 Photomicrograph of histopathology of the resected tumor.}

\textbf{(A, B)} Hematoxylin eosin stain (25x): invasive porocarcinoma
displays an intradermal proliferation with infiltrative borders and
atypical cytological features; \textbf{(C)} Hematoxylin eosin stain
(40x): The cytonuclear atypia are~clearly visible at higher
magnification.

\selectlanguage{english}
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