Cutaneous Manifestations of Internal Malignancy

1

List the five criteria that establish an association between a skin disease and internal malignancy.

Helen Curth, while evaluating acanthosis nigricans, established the five criteria known as Curth's postulates:

• 1.

  Concurrent onset of the cutaneous disease and internal malignancy.

• 2.

  Parallel course of the skin disease and internal malignancy.

• 3.

  A specific type or site of malignancy associated with the skin disease.

• 4.

  Sound statistical evidence that the malignancy is more frequent in patients with the skin disease.

• 5.

  A genetic link between a syndrome with skin manifestations and an internal malignancy.

2

Describe the clinical appearance of acanthosis nigricans.

Acanthosis nigricans appears as velvety, hyperpigmented, papillomatous, dirty-appearing skin. It is most frequently seen on the neck, axilla, groin, and dorsal hand surfaces. It is often associated with numerous skin tags and rarely affects mucosal surfaces ( Fig. 34.1 ).

3

What clinical disease states are associated with acanthosis nigricans?

Acanthosis nigricans is a common skin finding, reported in 7.1% of children, but more common in people with darker skin pigmentation, and is frequently associated with obesity and insulin resistance. Paraneoplastic acanthosis nigricans is rare and is most commonly associated with gastrointestinal cancer, especially gastric carcinoma. When associated with malignancy, it is usually abrupt in onset, is severe, and may involve mucous membranes and palmar skin (tripe palms). Paraneoplastic acanthosis nigricans is usually accompanied by weight loss.

Stuart CA, Pate CJ, Peters EJ. Prevalence of acanthosis nigricans in an unselected population. Am J Med. 1989;87(3):269–272.

4

Is the sign of Leser-Trélat (eruptive seborrheic keratoses) associated with internal malignancy?

The sign of Leser-Trélat is defined as the abrupt appearance of multiple seborrheic keratoses increasing in size and number caused by an associated cancer. This association remains controversial. Seborrheic keratoses are common in older patients, and so is cancer. Patients with Leser-Trélat often have coexisting paraneoplastic acanthosis nigricans and pruritus.

Schwartz R, Elston DM. The sign of Leser-Trélat. eMedicine Online. www.emedicine.com . Accessed April 23, 2018.

5

What is hypertrichosis lanuginosa?

Hypertrichosis lanuginosa (malignant down) is an acquired excessive growth of lanugo hair, usually on the face. Glossitis is frequently an associated finding. If anorexia nervosa or drug-related causes (such as minoxidil, diazoxide, and cyclosporine) can be excluded, there is a high association with internal malignancy, such as carcinoma of the lung, breast, and colon.

6

What is Sweet's syndrome?

Sweet's syndrome (acute febrile neutrophilic dermatosis) occurs mostly in women 30 to 60 years of age and consists of characteristic skin lesions, fever, malaise, and leukocytosis. Less commonly, there is involvement of the joints, eyes, lungs, kidneys, and liver. Approximately 20% of cases have an association with a hematologic malignancy, most commonly acute myelogenous leukemia.

7

Describe the cutaneous lesions of Sweet's syndrome.

The clinical hallmark of Sweet's syndrome is the presence of sharply demarcated, painful, juicy, edematous plaques on the face, neck, upper trunk, and extremities ( Fig. 34.2 ). Occasionally, papulovesicles and pustules are noted. Oral mucous membrane lesions are less common. Pathergy (lesions appearing in areas of trauma) can be seen.

8

Are any laboratory abnormalities found in Sweet's syndrome?

Leukocytosis with neutrophilia is common and present in 60% of patients. Elevated sedimentation rates and increased C-reactive protein levels are commonly seen.

9

What cancers are associated with Sweet's syndrome?

The most commonly associated malignancy is acute myelogenous leukemia, but chronic myelogenous leukemia, lymphocytic leukemia, T- and B-cell lymphomas, polycythemia, and, rarely, solid tumors also have been reported. Patients with persistent laboratory abnormalities, especially anemia, thrombocytosis, and thrombocytopenia, require close observation and thorough diagnostic evaluation.

Cohen PR. Sweet's syndrome—a comprehensive review of an acute febrile neutrophilic dermatosis. Orphanet J Rare Dis. 2007;2:34.

10

What other neutrophilic dermatosis can be associated with internal malignancy?

Pyoderma gangrenosum (PG) is an ulcerative skin disease with a distinctive clinical presentation. The lesions are painful, may rapidly enlarge, and are characterized by an erythematous or violaceous undermined border with a necrotic center ( Fig. 34.3 ). The most common diseases associated with PG are inflammatory bowel disease and rheumatoid arthritis. A small subset may have monoclonal immunoglobulin A (IgA) gammopathy and other hematologic disorders. In a review of several studies, PG was associated with internal malignancy in 7.2% of patients. Leukemia is the most frequently reported malignancy, with myelocytic and myelomonocytic leukemia accounting for the majority of cases.

Callen JP, Jackson JM. Pyoderma gangrenosum: an update. Rheum Dis Clin North Am. 2007;33:787–802.

11

What is necrolytic migratory erythema?

This characteristic skin eruption is associated with an α-cell tumor of the pancreas, and most patients have elevated glucagon serum levels (glucagonoma syndrome). It presents as erythema with superficial pustules and erosions, typically involving the face, intertriginous skin, and acral extremities ( Fig. 34.4 ). Weight loss, glossitis, stomatitis, and diabetes are frequent associations. Skin biopsy shows necrosis of the upper portion of the epidermis and is usually diagnostic.

Silva JA, Mesquita Kde C, Igreja AC, et al. Paraneoplastic cutaneous manifestations: concepts and updates. An Bras Dermatol. 2013;88(1):9–22.

12

What is the characteristic finding in erythema gyratum repens?

This rare skin eruption is characterized by a widespread figurate erythema composed of concentric rings with a wood grain appearance. The erythematous circinate lesions may have a fine scale and move up to 1 cm a day. Almost all patients with this unique dermatosis have an associated malignancy, most commonly carcinoma of the lung. It has also been reported with breast, bladder, cervical, and prostate cancers. The skin lesions clear within a few weeks after removal of the malignancy and usually recur if the cancer returns.

Ufkes N, Elston D. Erythema gyratum repens. eMedicine Online. www.emedicine.com . Accessed February 11, 2019.

13

What is Bazex syndrome (acrokeratosis paraneoplastica)?

This syndrome begins with acral violaceous psoriasiform plaques on the ears, nose, hands, and feet, likening to “blue psoriasis.” Paronychia and nail dystrophy are common. Later, the eruption may generalize, and lesions on the face may appear dermatitic or lupus-like. The syndrome is more common in men and is associated with squamous cell carcinoma of the upper aerodigestive tract ( Fig. 34.5 ).

There is another Bazex syndrome inherited as an autosomal dominant disease. This syndrome is characterized by follicular atrophoderma, early development of multiple facial basal cell carcinomas, and, in some patients, hypohidrosis.