Florid Cutaneous Papillomatosis

Updated: Apr 16, 2021
Author: Robert A Schwartz, MD, MPH; Chief Editor: Dirk M Elston, MD 



Florid cutaneous papillomatosis (FCP) is a disorder consisting of the rapid onset of numerous warty papules on the trunk and the extremities that are clinically indistinguishable from viral warts.[1, 2, 3, 4] Florid cutaneous papillomatosis was first described and the name florid cutaneous papillomatosis was coined in 1978 by Schwartz and Burgess.[5]

Florid cutaneous papillomatosis usually occurs in association with malignant acanthosis nigricans and an internal malignancy (see Acanthosis Nigricans).[6, 7] In fact, florid cutaneous papillomatosis is believed to be an obligatory paraneoplastic syndrome in that it has always been associated with an internal malignancy (see Paraneoplastic Diseases and Paraneoplastic Syndromes). The cancer, which is usually intra-abdominal and most often gastric in origin, tends to evolve in parallel with florid cutaneous papillomatosis.[8] The onset of florid cutaneous papillomatosis often becomes evident before or concurrent with the diagnosis of the internal tumor.

In a review of 46 patients, Stieler and Plewig[9] noted that each patient had an underlying cancer. The most common type was gastric adenocarcinoma, which occurred in more than half the patients. One patient had a gastric adenocarcinoma and a second malignancy, namely, breast adenocarcinoma. Other neoplasms that are reported to occur with florid cutaneous papillomatosis include other intra-abdominal tumors, such as cancer of the urinary bladder, biliary ducts, ovaries, and uterus; breast adenocarcinoma; squamous cell carcinoma of the lungs; and non-Hodgkin lymphoma.

Florid cutaneous papillomatosis occurs with signs of internal cancer. Although acanthosis nigricans and the sign of Leser-Trélat (ie, eruptive seborrheic keratoses) are most frequently linked to florid cutaneous papillomatosis, other signs, such as hypertrichosis lanuginosa acquisita, can be present.[10] See Sign of Leser-Trelat for more information on this topic.


The etiology of florid cutaneous papillomatosis is not known, as is the cause of the other 2 eruptive paraneoplastic syndromes that occur with florid cutaneous papillomatosis: malignant acanthosis nigricans and the sign of Leser-Trélat. These 3 paraneoplastic syndromes are probably directly induced by their underlying neoplasms, most likely by means of a tumor-secreted growth factor.[1]

In 1976, Millard and Gould[11] found high levels of immunoreactive human growth hormone in 2 patients with tylosis, one of whom had the sign of Leser-Trélat. In another report, a patient was described as having a small cutaneous melanoma, acanthosis nigricans, the sign of Leser-Trélat, and multiple acrochordons. In this patient, the lesions of the cutaneous paraneoplastic syndrome were stimulated by the epidermal growth factor receptor.[12] Increased epidermal staining for the epidermal growth factor receptor was initially noted in skin specimens of acanthosis nigricans, seborrheic keratoses, and cutaneous papillomas. Both the staining and the urine level of alpha-transforming growth factor markedly decreased after the primary nonmetastatic melanoma was removed. Alpha-transforming growth factor is structurally related to epidermal growth factor but antigenically distinct from it.

Florid cutaneous papillomatosis, malignant acanthosis nigricans, and the sign of Leser-Trélat should be viewed as part of a continuum. These conditions develop by means of a common or similar pathogenic pathway due to an underlying malignancy that produces a factor possibly similar to human epidermal growth factor.


The cause of florid cutaneous papillomatosis is not known. Florid cutaneous papillomatosis may be due to a tumor-secreted growth factor, although, to the author's knowledge, none has been identified (see Pathophysiology in Overview). Its association with acanthosis nigricans and the sign of Leser-Trélat suggests a common pathogenic mechanism.[13]



Florid cutaneous papillomatosis is a rare disease. So far, only about 25 patients have been reported.


From the limited number of patients described to date, florid cutaneous papillomatosis is almost twice as common in men than in women.


Florid cutaneous papillomatosis is usually diagnosed in individuals aged 53-72 years (mean patient age, 58.5 y).


Florid cutaneous papillomatosis is an obligate paraneoplastic syndrome, the underlying case is most commonly of gastric origin as documented in the 9 patients described since 2000.[2, 14]




The patient usually reports an eruption of wartlike growths. Unusually marked verrucous changes may cause disfigurement of the hands and feet.[15, 16]

Pruritus is an important sign that is evident in about one half of patients. Pruritus may precede the onset of florid cutaneous papillomatosis. It can occur in the affected regions, or it can be generalized.

The unsightly clinical appearance of florid cutaneous papillomatosis may result in social exclusion.[17]

Physical Examination

Clinically, the papulonodules of florid cutaneous papillomatosis are usually indistinguishable from common viral warts. The papulonodules begin on the extremities, particularly on the dorsa of the hands and the wrists. The papules may spread to involve the entire body, including the face. The papulonodules can be as large as 1 cm in diameter, or they can be as small as 2-3 mm in diameter. Pruritus may be associated. The esophagus may be involved.[18]

Florid cutaneous papillomatosis is usually associated with signs of internal cancer.[13] Malignant acanthosis nigricans develops eventually, many times with the sign of Leser-Trélat. Marked acanthosis nigricans, especially when associated with either florid cutaneous papillomatosis or so-called tripe palms, mandates a thorough search for malignancy.[19, 20, 21, 22, 23, 24] Florid cutaneous papillomatosis may be seen in patients with multiple visceral carcinomas[25] or with an adenocarcinoma of unknown primary site.[26]



Diagnostic Considerations

Verrucous mycosis fungoides may occasionally require distinction. Verrucous mucocutaneous acanthosis nigricans of the lips and buccal mucosa may represent, as described by Pentenero et al[27] in 2004, a patient with underlying cancer also beginning to develop florid cutaneous papillomatosis (FCP).

Florid papillomatosis of the nipple has been described, a change reminiscent of the hyperkeratosis of nipple sometimes associated with acanthosis nigricans.[28, 29] Histologically, florid papillomatosis of nipple represented an adenoma.

FCP would not be confused with oral florid papillomatosis.[30]

Differential Diagnoses



Histologic Findings

The cutaneous papillomas are uniform with pronounced hyperkeratosis, acanthosis, and papillomatosis. They lack evidence of epidermal vacuolization, parakeratosis, or eosinophilic inclusions suggestive of viral warts; however, patients in one study[31] did have these findings.

Results of ultrastructural evaluation, immunofluorescence tests, viral serologic tests, and DNA hybridization analyses to detect human papillomavirus in skin papillomas have been negative.[1] Accordingly, a viral origin is unlikely.

The principle concern in the differential diagnosis of florid cutaneous papillomatosis is viral warts. Florid cutaneous papillomatosis may morphologically resemble viral warts, but the microscopic changes in the granular layer of florid cutaneous papillomatosis are not present as they are in verruca vulgaris. The verrucous velvety pattern of malignant acanthosis nigricans facilitates the distinction, although acanthosis nigricans and florid cutaneous papillomatosis often occur together.

The sudden eruption of multiple seborrheic keratoses or the sign of Leser-Trélat may occur with acanthosis nigricans and florid cutaneous papillomatosis. Each seborrheic keratosis is a discrete verrucous nodule that appears as if it has been stuck on the skin. This nodule is easily distinguished from viral warts after careful scrutiny. However, patients have been reported to have oral acanthosis nigricans with multiple verrucouslike nodules on all of the extremities or rice- to pea-sized nodules on the trunk; these findings do not allow the reader to distinguish between the sign of Leser-Trélat and florid cutaneous papillomatosis.[32, 33]



Medical Care

Although follow-up evaluation has been limited in most reported cases of florid cutaneous papillomatosis (FCP), marked improvement of the cutaneous lesions was observed in seven patients after they underwent surgical or chemotherapeutic treatment of the internal cancer. Tumor recurrence may be associated with a recurrence of florid cutaneous papillomatosis.[34] In other cases, generalization of the cancer was associated with severe worsening of the cutaneous lesions.

To the author's knowledge, the palliative treatment of cutaneous papillomas has not produced any significant improvement, except in one patient in whom topical 5-fluorouracil was used. Such palliative treatments include systemic therapy with oral retinoids, radiation, or smallpox vaccination. Topical treatments with steroids, vitamin A acid, urea, salicylic acid, podophyllotoxin,[17] and liquid nitrogen have also been tried.

Long-Term Monitoring

Monitor patients for any recurrence of florid cutaneous papillomatosis (FCP) (assuming that it regresses after tumor therapy) because the reappearance of florid cutaneous papillomatosis can indicate a new tumor.