Florid cutaneous papillomatosis and acanthosis nigricans as cutaneous findings in a patient with ovarian carcinoma

To the Editor, A 49yearold female patient with an unremarkable personal medical history complained of the gradual onset of multiple itchy warty papules located on her face, trunk, and extremities, for almost 1 year. The patient had failed multiple wart treatments, including salicylic acid 36.3 mg/20 mm patch, cryotherapy, and CO2 laser. Physical examination showed the presence of numerous, fleshcolored, discrete papules with a verrucous surface either solitary on the trunk and dorsal hands and feet or clustered, for instance, along eyelid margins. A 4mm punch biopsy of the right axilla showed papillomatosis, hyperkeratosis, and acanthosis; no signs of viral inclusions were seen. The polymerase chain reaction for human papilloma viral DNA detection was performed using general GP5+/6+ on a specimen section, yielding negative results. The diagnosis of epidermodysplasia verruciformis was ruled out by negative HPV testing, including HPV5 and HPV8. In the followup visit, the patient developed velvety hyperpigmentation on the major folds, namely the armpits, groins, and neck, consistent with a diagnosis of acanthosis nigricans (AN) (Figure 1). Wood lamp examinations and bacterial and fungal swabs were negative. A complete blood count, liver and renal function, glucose and glycated hemoglobin, serum chemistry, urinalysis, and abdominal ultrasound were requested to investigate possible internal diseases. While most lab tests were within normal values, the cancer antigen 125 level turned elevated 625.5 U/mL (normal, <35 U/mL). The abdominal ultrasound examination showed a hypoechoic lesion involving both ovaries. The subsequent CT scan and MRI detected a 10 × 5 × 7 cm mass in the right ovary and a 5 × 6 × 4 cm mass in the left. Both of them involved nearby tissues, including the bowel, iliopsoas muscle, and ureters. The radical surgical excision yielded the histological diagnosis of a lowgrade ovarian serous carcinoma, and a chemotherapy regimen with carboplatin + paclitaxel every 3 weeks was initiated. After six cycles the patient achieved a complete remission and is now attending periodic followups for 1 year. Interestingly, all the warty lesions disappeared immediately after surgery, and the AN faded away in the following months. Florid cutaneous papillomatosis (FCP) is a paraneoplastic syndrome consisting of the sudden onset of numerous cutaneous warty lesions that are clinically indistinguishable from viral warts. FCP often presents accompanying signs such as malignant AN and LeserTrélat sign. The etiology of FCP and the other associated paraneoplastic syndromes is not yet fully understood, but they are all likely caused by a tumorsecreted epidermal growth factor.1 Acanthosis nigricans is a symmetric hyperpigmented and velvety cutaneous eruption that most commonly affects the axillae, groin, and sides of the neck. It has been associated with insulin resistance and is a common finding in obese patients suffering from metabolic syndrome.2 Less frequently, AN can be a spy of internal malignancies, and therefore is called malignant AN. Malignant AN is often associated with aggressive cancers, more often gastric, but it can be also caused by carcinomas of the uterus, intestines, liver, rectum,


Florid cutaneous papillomatosis and acanthosis nigricans as cutaneous findings in a patient with ovarian carcinoma
To the Editor, A 49-year-old female patient with an unremarkable personal medical history complained of the gradual onset of multiple itchy warty papules located on her face, trunk, and extremities, for almost 1 year. The patient had failed multiple wart treatments, including salicylic acid 36.3 mg/20 mm patch, cryotherapy, and CO 2 laser.
Physical examination showed the presence of numerous, fleshcolored, discrete papules with a verrucous surface either solitary on the trunk and dorsal hands and feet or clustered, for instance, along eyelid margins. A 4-mm punch biopsy of the right axilla showed papillomatosis, hyperkeratosis, and acanthosis; no signs of viral inclusions were seen. The polymerase chain reaction for human papilloma viral DNA detection was performed using general GP5+/6+ on a specimen section, yielding negative results.
The diagnosis of epidermodysplasia verruciformis was ruled out by negative HPV testing, including HPV5 and HPV8.
In the follow-up visit, the patient developed velvety hyperpigmentation on the major folds, namely the armpits, groins, and neck, consistent with a diagnosis of acanthosis nigricans (AN) (Figure 1).
Wood lamp examinations and bacterial and fungal swabs were negative.
A complete blood count, liver and renal function, glucose and glycated hemoglobin, serum chemistry, urinalysis, and abdominal ultrasound were requested to investigate possible internal diseases. While most lab tests were within normal values, the cancer antigen 125 level turned elevated 625.5 U/mL (normal, <35 U/mL).
The abdominal ultrasound examination showed a hypoechoic lesion involving both ovaries. The subsequent CT scan and MRI detected a 10 × 5 × 7 cm mass in the right ovary and a 5 × 6 × 4 cm mass in the left. Both of them involved nearby tissues, including the bowel, iliopsoas muscle, and ureters. The radical surgical excision yielded the histological diagnosis of a low-grade ovarian serous carcinoma, and a chemotherapy regimen with carboplatin + paclitaxel every 3 weeks was initiated. After six cycles the patient achieved a complete remission and is now attending periodic follow-ups for 1 year.
Interestingly, all the warty lesions disappeared immediately after surgery, and the AN faded away in the following months. colon, or ovary. It usually regresses after tumor remission but may recur in case of metastasis. 3,4 Florid cutaneous papillomatosis is a rare obligatory paraneoplastic syndrome and consists of multiple lesions beginning on the extremities and then disseminating to the entire body. Pruritus is an important accompanying symptom that should not be overlooked since it may precede the skin lesions. 5 FCP is most commonly associated with gastric adenocarcinoma but is also described in the lung, breast, bladder, uterus, ovary, and prostate cancers. 4 To our knowledge, this is the first case described of an asymptomatic ovarian serous carcinoma presenting with both AN and FCP at the time of the diagnosis. The recognition of this condition is essential to diagnose the associated malignancy early and start the appropriate treatment. The disappearance of skin lesions after obtaining complete cancer remission further confirmed their paraneoplastic genesis (Figure 2A-D).

ACK N OWLED G M ENTS
None declared.

E TH I C A L A PPROVA L
The authors confirm that the ethical policies of the journal, as noted on the journal's author guidelines page, have been adhered to.
Patient Informed Consent was obtained.

DATA AVA I L A B I L I T Y S TAT E M E N T
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.