Melanoma risk after in vitro fertilization: A review of the literature.

BACKGROUND: The role of female sex hormones in the pathogenesis of malignant melanoma (MM) remains controversial. Although melanocytes appear to be hormonally responsive, the effect of estrogen on MM cells is less clear. Available clinical data does not consistently demonstrate that increased endogenous hormones from pregnancy or increased exogenous hormones from oral contraceptive pills and hormone replacement affect MM prevalence and outcome. OBJECTIVE: We sought to examine potential associations between in vitro fertilization (IVF) and melanoma. METHODS: A literature review was conducted. Primary outcomes were reported as associations between IVF and melanoma risk compared with the general population. Secondary outcomes included associations stratified by type of IVF regimen and subgroup, such as parous versus nulliparous patients. RESULTS: Eleven studies met our inclusion criteria. Five studies found no increased risk for MM among IVF users compared with the general population. Two studies found an increase in MM in clomiphene users, and 4 studies found an increase in MM among patients who were gravid or parous either before or after IVF. CONCLUSION: The reviewed studies do not reveal consistent patterns of association between IVF and MM among all infertile women. However, the data indicates a potential increased risk for MM in ever-parous patients treated with IVF. High-quality studies including a large number of MM cases that control for well-established MM risk factors are needed to adequately assess the relationship between IVF and MM, particularly among ever-parous women.

Pregnancy and melanoma.

Malignant melanoma is the most common malignancy during pregnancy, and is diagnosed during childbearing age in approximately one-third of women diagnosed with melanoma. The impact of hormonal changes during pregnancy and from iatrogenic hormones on melanoma is controversial. Women undergo immunologic changes during pregnancy that may decrease tumor surveillance. In addition, hormone receptors are found on some melanomas. In spite of these observations, the preponderance of evidence does not support a poorer prognosis for pregnancy-associated melanomas. There is also a lack of evidence that oral contraceptives or hormone replacement therapy worsens melanoma prognosis.

Nevi and pregnancy.

Changes in the moles of pregnant women are frequently attributed to pregnancy, but recent studies suggest that pregnancy does not induce significant physiologic changes in nevi. It is common for nevi on the breasts and abdomen to grow with normal skin expansion, but studies that have examined melanocytic nevi on the backs or lower extremities have found no significant changes in size during pregnancy. Several studies have also investigated the belief that moles darken during pregnancy and have found insufficient evidence to support this idea. Dermoscopically, transient changes have been identified, but none are suggestive of melanoma. Results vary in terms of histologic changes seen in samples taken from pregnant women, but all authors agree that any histopathologic features consistent with melanoma should be viewed as melanoma and not attributed to pregnancy. Biopsy specimens should be obtained promptly from any changing mole that would raise concern for malignancy in a nonpregnant patient. Such procedures can be performed safely during pregnancy.

Idiopathic scleredema.

Scleredema, which also is known as scleredemaadultorum of Buschke, is an uncommonsclerodermiform condition that is characterizedby progressive thickening and hardening of theskin due to excessive dermal mucin and collagendeposition. The clinical course is variable, andprogression of disease may lead to functionalimpairment with limitations in mobility. The etiologyand pathogenesis are unknown although severalwell-known associations include streptococcalinfection; diabetes mellitus, particularly withmetabolic syndrome; and monoclonal gammopathy.We present a case of scleredema in a 52-year-oldman with no identifiable associated condition,who experienced improvemement with UVBphototherapy.

Scrotal lymphangioma circumscriptum.

Lymphangioma circumscriptum (LC) is anuncommon, benign, cutaneous disorder thatinvolves lymphatic dilatation to cause vesicularand papular lesions on the trunk, extremities, andanogenital areas. It may be a diagnostic challengewhen appearing in the anogenital region andoften is misdiagnosed and mistreated as infectiousetiologies, which include molluscum contagiosumand condylomata accuminata. We report a healthy40-year-old man with a six-month history of aneruption of multiple, asymptomatic, scrotal papulesthat were diagnosed as lymphangiomas. Awarenessof scrotal LC in adult men without prior disease orsymptoms is necessary for proper diagnosis andavoidance of unnecessary treatment.

Cowden syndrome presenting with trichilemmomas.

Cowden syndrome (CS) is a genetic cancerpredisposition syndrome that is associated withgermline mutations in the phosphate and tensinhomologue deleted on chromosome ten (PTEN)tumor suppressor gene. It is characterizedby the formation of benign and malignanttumors. Characteristic benign tumors includetrichilemmommas, acral keratoses, mucocutaneousneuromas, and oral papillomas. The most commonmalignant condition include breast, thyroid, andendometrial cancers. We present a case of a30-year-old woman with CS, who initially presentedwith trichilemmomas that were misdiagnosed ascomedonal acne. Recognition of the presentingfeatures of CS is important to ensure proper referral,management, and treatment for these patients.

Acral keratoses and squamous-cell carcinomas likely associated with arsenic exposure.

Chronic arsenic exposure is known to inducepunctate keratoses with an increased risk ofprimary squamous-cell carcinoma. Drinking wateris currently the major source of arsenic exposureworldwide and is considered one of the mostsubstantial environmental carcinogens. We describethe case of a 61-year-old Hungarian woman withscattered, acral, hyperkeratotic papules and a historyof five palmoplantar squamous-cell carcinomasas well as two other extremity non-melanomaskin cancers. Prior to immigration, she had livedin a county of Southern Hungary that is known tohave elevated concentrations of inorganic arsenicin the drinking water above the World HealthOrganization's current maximum threshold forsafety. To date, this report is the first to describethe phenomenon of palmoplantar squamouscellcarcinomas in a patient from this region andunderscores the importance of vigilant screening inthose individuals who have spent substantial time inhigh-risk regions internationally and domestically.

Darier-White disease.

We present a 58-year-old woman with bipolardisorder and with a longstanding history of yellowbrown,hyperkeratotic papules in a seborrheicdistribution and nail changes. Her father andpaternal grandmother had similar eruptions and alsohad psychiatric disease. Histopathologic examinationshowed acantholysis and dyskeratosis, which wasconsistent with Darier-White disease. Darier-Whitedisease is a rare, hereditary disorder that is inheritedin an autosomal dominant manner and that usuallypresents in adolescence or early adulthood dueto mutations in the SERCA2 calcium pump. Theresultant alterations in calcium homeostasis affectdesmosome assembly and lead to acantholysis andapoptosis, which creates the characteristic eruption.Genetic linkage analysis of affected families showsthat a susceptibility locus for bipolar disorder cosegregateswith genetic markers that are found inthe Darier-White disease region. Treatments, whichinclude topical emollients, mild keratolytics, andtopical or oral retinoids, are aimed at improvingthe appearance of skin, relieving symptoms, andpreventing or treating infectious complications.

Cutis verticis gyrata.

Cutis verticis gyrata that involves only the face isa rare presentation of this even rarer cutaneousanomaly. We present a 61-year-old man, whodeveloped primary essential progressive cutis verticisgyrata of the face.

Photodistributed granuloma annulare.

Annular elastolytic giant cell granuloma (AEGCG) is a controversial entity that is considered by many to be a variant of granuloma annulare (GA). The majority of cases of AEGCG occur in Caucasian women (3:2) between the ages of 40 and 70, with the distribution of the mostly annular lesions favoring exposed areas of skin and rarely involving covered skin. The most common systemic association has been with diabetes mellitus. We present a 52-year-old woman with an asymptomatic, annular, erythematous, photodistributed eruption of two-years duration. As part of her evaluation, it was detected that she had a hemoglobin A1C of 10.3% and a diagnosis of diabetes mellitus was made. We review the literature on the clinical and histopathologic features of GA and AEGCG and the overlap between these entities.

Extragenital bullous lichen sclerosus.

Lichen sclerosus (LS) is a chronic, inflammatory dermatosis that is characterized by pruritic, white, atrophic plaques that classically affect the anogenital region of postmenopausal women. Extragenital involvement also may occur with several reported morphologic variants. Extragenital bullous LS is a rare variant, which presents as flaccid bullae that favor the trunk and proximal aspects of the extremities. The treatment of extragenital bullous LS is similar to that of genital LS. However, extragenital LS is often less responsive and may present a therapeutic challenge. We describe a 65-year-old woman with a two-year history of vulvar and extragenital LS, who developed a bullous eruption within a pre-existing patch of lichen sclerosis on the breast. We review the clinical and histopathologic features of extragenital bullous LS and discuss current treatment options, which include those for recalcitrant cases.

Paraneoplastic erythema annulare centrifugum eruption (PEACE).

Erythema annulare centrifugum (EAC) is a reactive erythema with distinct, annular, erythematous plaques with trailing scale. This condition has been associated with various etiologies, which include an associated malignant condition. EAC with cancers or paraneoplastic erythema annulare centrifugum eruptions (PEACE), is more likely to be associated with lymphoproliferative malignancies such as lymphomas and leukemias. Histopathologic features include a superficial and deep, lymphohistiocytic perivascular infiltrate. We present a patient with a history of diffuse large B cell lymphoma in remission for two years, who presented with a one-year history of EAC.

Linear atrophoderma of Moulin.

We present a 40-year-old woman with asymptomatic, linear, hyperpigmented atrophic plaques in a Blaschkoid distribution on the right back and right upper extremity that is consistent with a diagnosis of linear atrophoderma of Moulin. Clinical lesions developed with a biphasic pattern in late adolescence and in adulthood. The pathogenesis of this acquired, progressive Blaschkolinear dermatosis may hold insight into the pathogenesis of this rare dermatologic condition, as well as other dermotoses, which include those resulting from post-zygotic genetic mosaicism.

IgA vasculitis (Henoch-Schönlein purpura).

We report the first case of direct immunoflourescence-proven immunoglobulin A (IgA) vasculitis associated with influenza infection in an adult patient. IgA vasculitis, which was previously known as Henoch-Schönlein purpura, is the most common systemic vasculitis in children but rarely occurs in adults. Disease onset often occurs after upper respiratory tract infections that are caused by adenovirus or enterovirus. The American College of Rheumatology defines IgA vasculitis by the presence of any two of the following four criteria: age ≤ 20 years at disease onset, palpable purpura, acute abdominal pain, and a biopsy specimen that shows granulocytes in the walls of small arterioles or venules. Purpura, abdominal pain, and arthralgia comprise the classic triad. Renal involvement may be severe, especially in adults. Treatment is most often supportive but glucocorticoids and/or immunosuppressive agents are recommended in severe or refractory cases.

Vulvar nevi, melanosis, and melanoma: an epidemiologic, clinical, and histopathologic review.

Pigmented vulvar lesions are present in approximately 1 in 10 women and include melanocytic and nonmelanocytic proliferations. Vulvar nevi, melanosis, and melanoma are particularly challenging because of the similarity of their clinical and/or histopathological presentation. As a result, they are often difficult to diagnose, may result in patient and physician anxiety, and can lead to unneeded, potentially disfiguring surgical procedures. Because it is often detected late, vulvar melanoma carries a poor prognosis with associated significant morbidity and mortality, underscoring the importance of prompt recognition and treatment. In this review, we analyze the distinct epidemiologic, clinical, and histopathologic characteristics of vulvar nevi, melanosis, and melanoma, discuss treatment options, and propose a practical, systematic approach to facilitate formulation of a differential diagnosis and initiation of appropriate management.

Collision tumor of eccrine poroma, seborrheic keratosis, and a viral wart.

A 68-year-old woman presented for evaluation of a large, red-brown plaque on her left buttock with irregular borders and prominent overlying verrucous changes. The plaque had been present since childhood but over a three-year period had been enlarging with increasing nodularity and easy bleeding with trauma. Histopathologic examination demonstrated an enlarged papillated and polypoid heterogeneous lesion. In part of the specimen, there are bulbous aggregates of small squamous cells with foci of eccrine ductal differentiation. There are other areas with horn pseudocysts, hypergranulosis, and compact orthokeratosis with parakeratosis. There are scattered enlarged heavily pigmented melanocytes, some of which have long and thick dendrites. This collision tumor consisted of an eccrine poroma, a seborrheic keratosis, and a viral wart. The clinical and histopathologic features of collision tumors and poromas are reviewed.

New world cutaneous leishmaniasis.

A 24-year-old Bangladeshi man presented with a 12-week history of a pruritic papule on his left elbow that had enlarged and ulcerated. He was without any constitutional or systemic symptoms. He reported a history of extensive travel in the two years prior to presentation that included Bangladesh, South and Central America, and Mexico. Histopathologic features were consistent with leishmaniasis. Speciation by the Centers for Disease Control showed L. brasiliensis.