Basaloid Follicular Hamartoma 

Updated: Dec 15, 2017
Author: Kara Melissa T Torres, MD, DPDS; Chief Editor: Dirk M Elston, MD 

Overview

Background

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 two 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] Unilateral and segmentally arranged basaloid follicular hamartomas are associated with Happle-Tinschert syndrome.[12, 13]

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, 14, 15, 16, 17] and nonfamilial systematized unilateral epithelial nevus.[11, 17]

Pathophysiology

Basaloid follicular hamartoma (BFH) is considered an abortive growth of secondary hair germs, with differentiation limited to the upper part of the follicles.[18]

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.[19, 20, 21] Genetic studies have implicated a patched (PTCH) gene mutation on band 9q23.[19, 22] The levels of PTCH 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.[20, 22]

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, 22, 23, 24]

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.[25]

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, 21, 26, 27, 28, 29, 30] 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.[23]

Age

Hereditary basaloid follicular hamartoma

The age of onset of basaloid follicular hamartoma (BFH) varies considerably.[7, 8, 9, 22, 23, 31]

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, 21, 26, 27, 28, 29, 30]

For linear unilateral basaloid follicular hamartoma (LUBFH), the majority of reported patients displayed basaloid follicular hamartoma at birth or in early childhood.[25, 32] Rarely, the onset of lesions has been documented as late as the second decade of life.[33, 34]

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.[23]

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.[17, 35, 33]

 

Presentation

History

In general, basaloid follicular hamartoma (BFH) lesions are asymptomatic small papules that remain stable for many years.[22] In hereditary basaloid follicular hamartoma, the lesions may gradually increase in size throughout childhood and then stabilize and become static upon reaching adulthood.[9, 31]

Generalized basaloid follicular hamartoma syndrome (GBFHS) is most commonly associated with alopecia and myasthenia gravis.[2, 36] Other associations reported with the syndrome are systemic lupus erythematosus (SLE),[2] cystic fibrosis,[4] and chondrosarcoma.[11]

Physical Examination

The skin lesions of basaloid follicular hamartoma (BFH) may present as macules, papules, nodules, plaques, or skin tags.[2, 9, 37]

Hereditary basaloid follicular hamartoma

Lesions most often manifest on the face and scalp. The lesions also commonly develop diffusely on the skin of the neck, back, chest, and extremities.[9] Patients may have few to hundreds of lesions. Most commonly, they appear as 1- to 2-mm flesh-colored papules. However, hyperpigmented or hypopigmented lesions are not uncommon.[9, 22] Palmar pitting has been documented in some cases of hereditary basaloid follicular hamartoma.[9, 22, 24]

Additional clinical features associated with generalized basaloid follicular hamartoma syndrome (GBFHS), especially those with no systemic affection, include milia and comedonelike papules,[14] hypohidrosis,[36] alopecia or hypotrichosis, and dermatosis papulosa nigra–like growths.[9] Generalized basaloid follicular hamartoma syndrome has also been reportedly associated in a patient with acrochordons, seborrheic keratoses, and a history of chondrosarcoma.[11]

Linear unilateral basaloid follicular hamartoma (LUBFH) displays multiple flesh-colored to pigmented lesions in a linear, bandlike pattern running along the lines of Blaschko.[2] In their early stages, the lesions may be hypopigmented, smooth, and striaelike. Lesional skin in an atypical case of linear unilateral basaloid follicular hamartoma was described as an atrophic, depressed patch.[25] A patient with linear unilateral basaloid follicular hamartoma with an unusual and extensive proliferation of trichoblastoma has also been reported.[38]

Acquired basaloid follicular hamartoma

The papules or plaques of basaloid follicular hamartoma are found on the eyelids, face, and scalp.[23, 39] The lesions may range from 0.1 cm to 3 cm. They may appear hypopigmented, hyperpigmented, or flesh colored. Hypotrichosis or alopecia may develop at sites of solitary basaloid follicular hamartoma. A case of a localized basaloid follicular hamartoma arising in an epithelioid blue nevus has been reported.[40]

Complications

Although rare, malignant transformation in the basaloid follicular hamartoma (BFH) lesions in generalized basaloid follicular hamartoma syndrome (GBFHS)[41] and within a localized basaloid follicular hamartoma[42] has been reported. Continual monitoring is imperative.

 

DDx

Diagnostic Considerations

The clinical differential diagnoses of solitary/localized basaloid follicular hamartoma (BFH) includes the following[2, 17, 23, 39] :

  • Basal cell carcinoma (BCC)

  • Trichoepithelioma

  • Fibroepithelioma of Pinkus

  • Folliculocentric basaloid proliferation

  • Trichofolliculoma

  • Fibrofolliculoma

  • Trichoblastic fibroma

  • Tumor of the follicular infundibulum

  • Melanocytic nevus

  • Seborrheic keratosis

  • Sebaceous hyperplasia

  • Poroma

  • Merkel cell carcinoma

  • Hair follicle nevus

  • Nevus sebaceous (scalp localization)

  • Lupus erythematosus (scalp localization)

  • Sarcoidosis (scalp localization)

  • Alopecia neoplastica (scalp localization)

The clinical differential diagnoses of multiple basaloid follicular hamartoma/generalized basaloid follicular hamartoma syndrome (GBFHS) includes the following[2, 9, 23] :

  • Nevoid basal cell carcinoma syndrome (NBCCS)

  • Multiple infundibulocystic basal cell carcinoma

  • Multiple trichoepithelioma

  • Cowden syndrome (trichilemmomas)

  • Birt-Hogg-Dubé syndrome (trichodiscomas, fibrofolliculomas)

  • Tuberous sclerosis (angiofibromas)

  • Eruptive syringoma

  • Multiple minute digitate hyperkeratoses

  • Generalized keratoacanthoma

  • Bazex-Dupré-Christol syndrome

  • Rombo syndrome

The clinical differential diagnoses of linear unilateral basaloid follicular hamartoma (LUBFH) includes the following[33, 25, 32] :

  • Linear unilateral basal cell nevus

  • Linear epidermal nevus

  • Lichen striatus

  • Linear trichoepithelioma

  • Unilateral nevoid basal cell carcinoma syndrome

  • Linear syringoma

  • Nevus comedonicus

  • Linear eccrine nevus

  • Linear morphea

The histological differential diagnoses of basaloid follicular hamartoma includes the following[17] :

  • Trichoepithelioma

  • Basal cell carcinoma

  • Infundibulocystic basal cell carcinoma

  • Fibroepithelioma of Pinkus

  • Fibrofolliculoma

  • Trichofolliculoma

  • Hair follicle nevus

  • Nevus sebaceous

  • Trichoblastic fibroma

Differential Diagnoses

 

Workup

Laboratory Studies

No specific tests are required to establish a diagnosis of basaloid follicular hamartoma (BFH) other than skin biopsy. However, given the association between multiple basaloid follicular hamartoma and autoimmune diseases such as systemic lupus erythematosus (SLE) and myasthenia gravis, a comprehensive history and physical examination should be performed. If the clinical index of suspicion for autoimmune disease is strong, the following laboratory tests may be ordered:

  • Antinuclear antibody testing

  • Double-stranded (ds) DNA antibody testing

  • Ro (ssA) and La (ssB) antibody testing

  • CBC count with differential

  • Urinalysis

  • Chemistry panel

  • Complement levels

  • Antiacetylcholine antibody testing

Patients may present clinically with nevoid basal cell carcinoma syndrome (NBCCS) with overlapping features of basaloid follicular hamartoma. To avoid excessive surgical treatment should the lesion be a benign basaloid follicular hamartoma, the identification of a de novo mutation of c.1291delC in the PTCH1 gene helps to confirm the diagnosis of nevoid basal cell carcinoma syndrome.[43]

Imaging Studies

Imaging studies may be useful to distinguish patients with multiple basaloid follicular hamartoma (BFH) from those with nevoid basal cell carcinoma syndrome (NBCCS). Specifically, nevoid basal cell carcinoma syndrome patients may display odontogenic jaw keratocysts, intracranial calcification (eg, of the falx cerebri), and rib anomalies. The following specific studies may be obtained to identify patients suggested of having nevoid basal cell carcinoma syndrome:

  • Panorex films of the jaw

  • Skull radiography

  • Chest radiography

Other Tests

If the clinical index of suspicion is high that a patient with multiple basaloid follicular hamartoma (BFH) has myasthenia gravis, electromyography may be obtained.

Procedures

Skin biopsy is important for distinguishing basaloid follicular hamartoma (BFH) lesions from other lesions in the differential diagnoses.

Histologic Findings

The definitive diagnosis of basaloid follicular hamartoma (BFH) is based on histologic findings. Despite the wide range of clinical manifestations, the histologic features of basaloid follicular hamartoma are relatively consistent for all its forms.[44, 45, 46] See the image below.

Basaloid follicular hamartoma. Courtesy of L Wozni Basaloid follicular hamartoma. Courtesy of L Wozniak & KW Zielinski (own work), via Wikimedia Commons.

Anastomosing thick cords and thin strands of basaloid cells are localized to the superficial dermis.[17, 47] In contrast, infundibulocystic basal cell carcinoma (BCC) may involve the subcutaneous fat and skeletal muscle.[47]

Lesions of basaloid follicular hamartoma are unattached to the epidermis and extend from the infundibular portion of vellus hair follicles.[22]

Mitoses and single cell necrosis are generally few, if at all present, in basaloid follicular hamartoma.[22, 23, 48] A prominence of these findings is more consistent with basal cell carcinoma.[22, 23]

The stroma in basaloid follicular hamartoma is mildly cellular and fibromyxoid.[17, 23] The peritumoral stroma was found to have positive CD34 and CD10 staining.[39, 48, 49]

Specific immunostaining studies may help to distinguish basaloid follicular hamartoma from basal cell carcinoma. Basaloid follicular hamartoma has a lower cell proliferative index of the proliferative cell nuclear antigen (PCNA) and Ki-67 compared with basal cell carcinoma.[22, 48] Basaloid follicular hamartoma also has positive immunoreactivity to CK20 and plectin homology–like domain, family A, and member 1 protein (PHLDA1) that is typically negative in basal cell carcinoma.[1] Bcl-2 is positive only within the outermost cells bordering the stroma in basaloid follicular hamartoma, in contrast to a significant bcl-2 expression found in the more aggressive forms of basal cell carcinoma.[39, 49, 50, 51] Other positive stains that may be seen in basaloid follicular hamartoma are S100 in the epithelial nests and stroma and factor VIIIa in the dendritic cells adjacent to the epithelial nests.[18]

 

Treatment

Medical Care

Systemic isotretinoin has been reported to decrease the size of lesions and improve associated alopecia in a patient with multiple basaloid follicular hamartoma (BFH) and systemic lupus erythematosus (SLE).[21] 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.[17, 35, 33]

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.[52] This form of therapy is considered the treatment of choice in children.

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).[42] Biopsy should be performed on lesions if they change size or appearance.

 

Medication

Medication Summary

No medications have been approved for basaloid follicular hamartoma (BFH) treatment.