Practice Essentials
Basaloid follicular hamartoma (BFH) is a rare, benign adnexal tumor. A variety of clinical patterns have been noted with identical histopathologic features and possible associations with numerous disorders. The tumor is morphologically similar to infundibulocystic basal cell carcinoma. [1]
In general, basaloid follicular hamartomas occur in 2 forms: hereditary and acquired. Hereditary types of basaloid follicular hamartoma can be either generalized or localized. Acquired types of basaloid follicular hamartoma can be localized, solitary, or multiple.
Hereditary basaloid follicular hamartomas
Generalized basaloid follicular hamartoma syndrome (GBFHS) subtype is inherited in an autosomal dominant pattern and has additional cutaneous features that include milia, comedonelike lesions, alopecia or hypotrichosis, and hypohidrosis. The syndrome is usually associated with some autoimmune disease, [2, 3, 4] but widespread lesions with no associated systemic disorders also have been reported. [2] When multiple basaloid follicular hamartomas are associated specifically with myasthenia gravis and diffuse alopecia, the syndrome is known as Brown-Crounse syndrome. [5]
Linear unilateral basaloid follicular hamartoma (LUBFH) subtype is also known as linear unilateral basal cell nevus with comedones, linear unilateral basal cell nevus, and basal cell and linear unilateral adnexal hamartoma. [6] The lesions associated with linear unilateral basaloid follicular hamartoma occur along the lines of Blaschko in a limited, mosaic pattern. [2, 7]
Familial multiple basaloid familiar hamartoma type of is an autosomal dominant disease that may or may not have the clinical features of hypotrichosis, hypohidrosis, and palmoplantar pitting. [2, 8, 9]
Other hereditary syndromes are recognized. Multiple basaloid follicular hamartomas have been reported to be associated with the nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome or basal cell nevus syndrome, [10] and Bazex-Dupré-Christol syndrome. [11] BFH is sometimes considered a required diagnostic component of NBCCS. [12] Unilateral and segmentally arranged basaloid follicular hamartomas are associated with Happle-Tinschert syndrome. [13, 14]
Acquired basaloid follicular hamartomas
Solitary/localized lesions are the usual presentations of acquired basaloid follicular hamartoma.
There are few reported cases of multiple basaloid follicular hamartomas with no evidence of autosomal dominance inheritance [11, 15, 16, 17, 18] and nonfamilial systematized unilateral epithelial nevus. [11, 18]
Signs and symptoms
The skin lesions of basaloid follicular hamartoma (BFH) may present as macules, papules, nodules, plaques, or skin tags. [2, 9, 19]
In general, basaloid follicular hamartoma (BFH) lesions are asymptomatic small papules that remain stable for many years. [20] In hereditary basaloid follicular hamartoma, the lesions may gradually increase in size throughout childhood and then stabilize and become static upon reaching adulthood. [9, 21]
Generalized basaloid follicular hamartoma syndrome (GBFHS) is most commonly associated with alopecia and myasthenia gravis. [2, 22] Other associations reported with the syndrome are systemic lupus erythematosus (SLE), [2] cystic fibrosis, [4] and chondrosarcoma. [11]
For a full discussion, see Physical Examination.
Complications
Although rare, malignant transformation in the basaloid follicular hamartoma (BFH) lesions in generalized basaloid follicular hamartoma syndrome (GBFHS) [23] and within a localized basaloid follicular hamartoma [24] has been reported. Continual monitoring is imperative.
Del Barrio-Diaz et al have suggested that local inflammation of BFH lesions is a clinical sign of malignant transformation. [25]
Diagnostics
Skin biopsy is important for distinguishing basaloid follicular hamartoma (BFH) lesions from other lesions in the differential diagnoses.
On dermoscopy with polarized light, one case of linear BFH showed as white-colored globules of various dimension with some globules exhibiting brownish clods or smaller globules and 1-2 central fine hairs. The globules occurred on a network of dense brown pigment and eccrine openings. [26]
If the clinical index of suspicion is high that a patient with multiple basaloid follicular hamartoma (BFH) has myasthenia gravis, electromyography may be obtained.
For a full discussion, including histopathology, see Workup.
Treatment
Although no medications have been approved for basaloid follicular hamartoma (BFH) treatment, systemic isotretinoin has been reported to decrease the size of lesions and improve associated alopecia in a patient with multiple BFH and systemic lupus erythematosus (SLE). [27] Topical tazarotene 0.1% gel maintained hair regrowth after discontinuation of isotretinoin therapy. However, the potential for adverse effects with long-term usage, lack of information on long-term benefits, and paucity of reported cases treated with isotretinoin warrant caution. If associated with an autoimmune disease, treatment of the primary disease may result in clinical improvement of the cutaneous lesions.
Surgical care
Basaloid follicular hamartomas (BFHs) are typically indolent and innocuous lesions. They may be excised for cosmetic reasons. Nonetheless, basaloid follicular hamartoma lesions should be excised if suspicious changes develop. [18, 28, 29]
Effective treatment of widespread, numerous basaloid follicular hamartoma was achieved in a nevoid basal cell carcinoma syndrome (NBCCS) patient using photodynamic therapy with topical 5-aminolevulinic acid, either in a filtered tungsten-halogen lamp (590-700 nm) or argon dye–pumped laser. [30] This form of therapy is considered the treatment of choice in children.
Both carbon dioxide laser [31] and pulsed dye laser [32] therapy have been reportedly used in BFH cases for cosmetic concerns with good results.
Consultations
A rheumatologist should be consulted for patients with multiple basaloid follicular hamartomas (BFHs) who manifest features of systemic lupus erythematosus (SLE). Similarly, a neurologist should be consulted for patients with multiple basaloid follicular hamartomas suspected of having myasthenia gravis.
Long-term monitoring
Follow-up visits for monitoring basaloid follicular hamartoma (BFH) lesions may be considered given rare reports of the development of basal cell carcinoma (BCC). [24] Biopsy should be performed on lesions if they change size or appearance.
Background
Pathophysiology
Basaloid follicular hamartoma (BFH) is considered an abortive growth of secondary hair germs, with differentiation limited to the upper part of the follicles. [33]
The causative gene for this hamartoma is still unknown. Deregulation of the sonic hedgehog (SHH) signaling pathway, which is central to the pathogenesis of basal cell carcinoma (BCC), with increased Gli-1 transcription, has been implicated in its pathogenesis. [34, 35, 27] Genetic studies have implicated a patched (PTCH1) gene mutation on band 9q22.3-q31. [34, 20, 36, 37] The levels of PTCH1 mRNA were found to be significantly lower in basaloid follicular hamartoma compared with basal cell carcinoma, suggesting that the magnitude of SHH signaling strongly influences tumor phenotype. [35, 20] Blanchard et al concluded that PTCH1 inactivation alone can cause basaloid follicular hamartoma in the setting of pediatric NBCCS. [38]
BFH has been reported in association with follicular mucinosis and inflammation. [39]
Basaloid follicular hamartoma may be histologically identical to infundibulocystic basal cell carcinoma. In addition to findings on hematoxylin and eosin (H&E) staining, both entities were found to have positive CK20 staining, suggesting that basaloid follicular hamartoma and infundibulocystic basal cell carcinoma might actually represent the same lesion. [1]
Etiology
No gene defect that confers specific increased susceptibility to basaloid follicular hamartoma (BFH) for the hereditary or acquired forms has been identified. [8, 9, 20, 40, 41]
Linear unilateral basaloid follicular hamartoma (LUBFH) is believed to be caused by a postzygotic, somatic mutation during embryogenesis in an as-yet unidentified gene. This gene defect would therefore be present only in cells derived from the precursor cell that acquired the mutation, accounting for the mosaic, linear, and unilateral pattern following the lines of Blaschko. [42]
Epidemiology
Frequency
Both hereditary and nonhereditary forms of multiple basaloid follicular hamartoma (BFH) and linear unilateral basaloid follicular hamartoma (LUBFH) are very rare. No records describe an annual incidence or prevalence for basaloid follicular hamartoma. Sporadic cases are observed, but must be differentiated from infundibulocystic basal cell carcinoma (BCC). The incidence may be underappreciated in the general population, given its limited distribution and benign nature.
Race
Basaloid follicular hamartoma (BFH) has been reported worldwide in people of various races and ethnic backgrounds, including Latin Americans, [8] African Americans, [9] East Asians, [3] Egyptians, [2] and whites.
Sex
Hereditary basaloid follicular hamartoma
Reported cases of multiple basaloid follicular hamartomas (BFHs) associated with systemic lupus erythematosus (SLE) or myasthenia gravis involve only female patients. [3, 5, 27, 43, 44, 45, 46, 47] Other presentations of hereditary and nonhereditary multiple basaloid follicular hamartoma appear to be equally distributed between men and women.
Acquired basaloid follicular hamartoma
In a report describing 56 patients, basaloid follicular hamartoma was documented most frequently in middle-aged or elderly women. [40]
Age
Hereditary basaloid follicular hamartoma
The age of onset of basaloid follicular hamartoma (BFH) varies considerably. [7, 8, 9, 20, 40, 21]
For multiple basaloid follicular hamartomas associated with autoimmune disease, the onset typically occurs in early adulthood, ranging in age from 20-33 years. Most patients showed onset of basaloid follicular hamartoma simultaneously with or soon after the diagnosis of an autoimmune disease was established. [3, 5, 27, 43, 44, 45, 46, 47]
For linear unilateral basaloid follicular hamartoma (LUBFH), the majority of reported patients displayed basaloid follicular hamartoma at birth or in early childhood. [42, 48] Rarely, the onset of lesions has been documented as late as the second decade of life. [29, 49]
Acquired basaloid follicular hamartoma
Lesions typically manifest later in life. Published cases report the age of onset ranging from 20-88 years, with a median of 66 years and a mean of 63 years. [40]
Prognosis
The prognosis for basaloid follicular hamartoma (BFH) is usually excellent, unless associated systemic disorders and/or basal cell carcinoma (BCC) develop. Basaloid follicular hamartomas are generally benign, superficial, and stable lesions; however, they may be unsightly or of cosmetic concern to patients. Rarely, the development of basal cell carcinoma within basaloid follicular hamartoma lesions has been reported. [18, 28, 29]
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Basaloid follicular hamartoma. Courtesy of L Wozniak & KW Zielinski (own work), via Wikimedia Commons.
