Dirk M. Elston, MD

The Diagnosis: Idiopathic Guttate Hypomelanosis

A biopsy of the largest lesion from the left leg 
superior to the lateral malleolus was performed. 
 Histopathologic examination revealed solar elastosis, diminished number of focal melanocytes and pigment within keratinocytes compared to uninvolved skin, and presence of hyperkeratosis with flattening of rete ridges. The clinical presentation along with histopathologic analysis confirmed a diagnosis of idiopathic guttate hypomelanosis (IGH). The lesions were treated with short-exposure cryotherapy, which resulted in partial repigmentation after several treatments.

Idiopathic guttate hypomelanosis is a common but underreported condition in elderly patients that usually presents with small, discrete, asymptomatic, hypopigmented macules. The frequency of IGH increases with age.¹ Frequency of the condition is much lower in patients aged 21 to 30 years and does not exceed 7%. Lesions of IGH have a predilection for sun-exposed areas such as the arms and legs but rarely can be seen on the face and trunk. Facial lesions of IGH are more frequently reported in women.¹ The size of lesions can be up to 1.5 cm in diameter. The condition generally is self-limited, but some patients may express aesthetic concerns. Rare cases of IGH in children have been associated with prolonged sun exposure.²

The etiology of IGH is unknown but an association with sun exposure has been noted. Patients with IGH frequently show other signs of photoaging, such as numerous seborrheic keratoses, solar lentigines, xeroses, freckles, and actinic keratoses.¹ Short-term exposure to UVB radiation and psoralen plus UVA therapy has been shown to cause IGH in patients with chronic diseases such as mycosis fungoides.^3-5 One small study that examined renal transplant recipients determined an association between HLA-DQ3 antigens and IGH, whereas HLA-DR8 antigens were not identified in any patients with IGH, indicating it may have some advantage in preventing the development of IGH.⁶ Shin et al¹ reported that IGH was prevalent among patients who regularly traumatized their skin by scrubbing.

Clinically, IGH should be differentiated from other conditions characterized by hypopigmentation, such as pityriasis alba, pityriasis versicolor, postinflammatory hypopigmentation, progressive macular hypomelanosis, and vitiligo. Aside from clinical examination, histopathologic studies are helpful in making a definitive diagnosis. The differential diagnosis of IGH is presented in the Table.

Histopathology of IGH lesions usually reveals slight atrophy of the epidermis with flattening of rete ridges and concomitant hyperkeratosis. A thickened stratum granulosum also has been noted in lesions of IGH.² The diminished number of melanocytes and melanin pigment granules along with hyperkeratosis both appear to contribute to the hypopigmentation noted in IGH.⁷ Ultrastructural studies of lesions of IGH can confirm melanocytic degeneration and a decreased number of melanosomes in melanocytes and keratinocytes.^2,8

There is no uniformly effective treatment of IGH. Topical application of tacrolimus and tretinoin have shown efficacy in repigmenting IGH lesions.^8,9 Short-exposure cryotherapy with a duration of 3 to 
5 seconds, localized chemical peels, and/or local dermabrasion can be helpful.^10-12 CO₂ lasers also have demonstrated promising results.¹³

The Diagnosis: Idiopathic Guttate Hypomelanosis

A biopsy of the largest lesion from the left leg 
superior to the lateral malleolus was performed. 
 Histopathologic examination revealed solar elastosis, diminished number of focal melanocytes and pigment within keratinocytes compared to uninvolved skin, and presence of hyperkeratosis with flattening of rete ridges. The clinical presentation along with histopathologic analysis confirmed a diagnosis of idiopathic guttate hypomelanosis (IGH). The lesions were treated with short-exposure cryotherapy, which resulted in partial repigmentation after several treatments.

Idiopathic guttate hypomelanosis is a common but underreported condition in elderly patients that usually presents with small, discrete, asymptomatic, hypopigmented macules. The frequency of IGH increases with age.¹ Frequency of the condition is much lower in patients aged 21 to 30 years and does not exceed 7%. Lesions of IGH have a predilection for sun-exposed areas such as the arms and legs but rarely can be seen on the face and trunk. Facial lesions of IGH are more frequently reported in women.¹ The size of lesions can be up to 1.5 cm in diameter. The condition generally is self-limited, but some patients may express aesthetic concerns. Rare cases of IGH in children have been associated with prolonged sun exposure.²

The etiology of IGH is unknown but an association with sun exposure has been noted. Patients with IGH frequently show other signs of photoaging, such as numerous seborrheic keratoses, solar lentigines, xeroses, freckles, and actinic keratoses.¹ Short-term exposure to UVB radiation and psoralen plus UVA therapy has been shown to cause IGH in patients with chronic diseases such as mycosis fungoides.^3-5 One small study that examined renal transplant recipients determined an association between HLA-DQ3 antigens and IGH, whereas HLA-DR8 antigens were not identified in any patients with IGH, indicating it may have some advantage in preventing the development of IGH.⁶ Shin et al¹ reported that IGH was prevalent among patients who regularly traumatized their skin by scrubbing.

Clinically, IGH should be differentiated from other conditions characterized by hypopigmentation, such as pityriasis alba, pityriasis versicolor, postinflammatory hypopigmentation, progressive macular hypomelanosis, and vitiligo. Aside from clinical examination, histopathologic studies are helpful in making a definitive diagnosis. The differential diagnosis of IGH is presented in the Table.

Histopathology of IGH lesions usually reveals slight atrophy of the epidermis with flattening of rete ridges and concomitant hyperkeratosis. A thickened stratum granulosum also has been noted in lesions of IGH.² The diminished number of melanocytes and melanin pigment granules along with hyperkeratosis both appear to contribute to the hypopigmentation noted in IGH.⁷ Ultrastructural studies of lesions of IGH can confirm melanocytic degeneration and a decreased number of melanosomes in melanocytes and keratinocytes.^2,8

There is no uniformly effective treatment of IGH. Topical application of tacrolimus and tretinoin have shown efficacy in repigmenting IGH lesions.^8,9 Short-exposure cryotherapy with a duration of 3 to 
5 seconds, localized chemical peels, and/or local dermabrasion can be helpful.^10-12 CO₂ lasers also have demonstrated promising results.¹³

The Diagnosis: Idiopathic Guttate Hypomelanosis

A biopsy of the largest lesion from the left leg 
superior to the lateral malleolus was performed. 
 Histopathologic examination revealed solar elastosis, diminished number of focal melanocytes and pigment within keratinocytes compared to uninvolved skin, and presence of hyperkeratosis with flattening of rete ridges. The clinical presentation along with histopathologic analysis confirmed a diagnosis of idiopathic guttate hypomelanosis (IGH). The lesions were treated with short-exposure cryotherapy, which resulted in partial repigmentation after several treatments.

Idiopathic guttate hypomelanosis is a common but underreported condition in elderly patients that usually presents with small, discrete, asymptomatic, hypopigmented macules. The frequency of IGH increases with age.¹ Frequency of the condition is much lower in patients aged 21 to 30 years and does not exceed 7%. Lesions of IGH have a predilection for sun-exposed areas such as the arms and legs but rarely can be seen on the face and trunk. Facial lesions of IGH are more frequently reported in women.¹ The size of lesions can be up to 1.5 cm in diameter. The condition generally is self-limited, but some patients may express aesthetic concerns. Rare cases of IGH in children have been associated with prolonged sun exposure.²

The etiology of IGH is unknown but an association with sun exposure has been noted. Patients with IGH frequently show other signs of photoaging, such as numerous seborrheic keratoses, solar lentigines, xeroses, freckles, and actinic keratoses.¹ Short-term exposure to UVB radiation and psoralen plus UVA therapy has been shown to cause IGH in patients with chronic diseases such as mycosis fungoides.^3-5 One small study that examined renal transplant recipients determined an association between HLA-DQ3 antigens and IGH, whereas HLA-DR8 antigens were not identified in any patients with IGH, indicating it may have some advantage in preventing the development of IGH.⁶ Shin et al¹ reported that IGH was prevalent among patients who regularly traumatized their skin by scrubbing.

Clinically, IGH should be differentiated from other conditions characterized by hypopigmentation, such as pityriasis alba, pityriasis versicolor, postinflammatory hypopigmentation, progressive macular hypomelanosis, and vitiligo. Aside from clinical examination, histopathologic studies are helpful in making a definitive diagnosis. The differential diagnosis of IGH is presented in the Table.

Histopathology of IGH lesions usually reveals slight atrophy of the epidermis with flattening of rete ridges and concomitant hyperkeratosis. A thickened stratum granulosum also has been noted in lesions of IGH.² The diminished number of melanocytes and melanin pigment granules along with hyperkeratosis both appear to contribute to the hypopigmentation noted in IGH.⁷ Ultrastructural studies of lesions of IGH can confirm melanocytic degeneration and a decreased number of melanosomes in melanocytes and keratinocytes.^2,8

There is no uniformly effective treatment of IGH. Topical application of tacrolimus and tretinoin have shown efficacy in repigmenting IGH lesions.^8,9 Short-exposure cryotherapy with a duration of 3 to 
5 seconds, localized chemical peels, and/or local dermabrasion can be helpful.^10-12 CO₂ lasers also have demonstrated promising results.¹³

The coexistence of more than one cutaneous adnexal neoplasm in a single biopsy specimen is unusual and is most frequently recognized in the context of a nevus sebaceous or Brooke-Spiegler syndrome, an autosomal-dominant inherited disease characterized by cutaneous adnexal neoplasms, most commonly cylindromas and trichoepitheliomas.^1-3 Brooke-Spiegler syndrome is caused by germline mutations in the cylindromatosis gene, CYLD, located on band 16q12; it functions as a tumor suppressor gene and has regulatory roles in development, immunity, and inflammation.¹ Weyers et al³ first recognized the tendency for adnexal collision tumors to present in patients with Brooke-Spiegler syndrome; they reported a patient with Brooke-Spiegler syndrome with spiradenomas found in the immediate vicinity of trichoepitheliomas and in continuity with hair follicles.

Spiradenomas are composed of large, sharply demarcated, rounded nodules of basaloid cells with little cytoplasm (Figure 1).⁴ The basaloid nodules may demonstrate a trabecular architecture, and on close inspection 2 cell types—paler cells with more cytoplasm and darker cells with less cytoplasm—are distinguishable (Figure 2A). Lymphocytes often are scattered within the tumor nodules and/or stroma. In Brooke-Spiegler syndrome, collision tumors containing a spiradenomatous component in collision with trichoepithelioma are not uncommon.¹ Spiradenomas in Brooke-Spiegler syndrome have been reported to contain sebaceous differentiation or foci with an adenoid cystic carcinoma (ACC)–like pattern and are known to occur as hybrid lesions of spiradenoma and cylindroma or trichoepithelioma (as in this case).

Figure 1. Two distinct neoplasms are apparent, side by side, with an intervening hair follicle. The spirade-noma (right) is a large, sharply demarcated, rounded nodule of basaloid cells containing little cytoplasm. The trichoepithelioma (left) is composed of lobules of basaloid cells with a cribriform architecture, surrounded by a fibroblast-rich stroma. Mucin is apparent within the cystic spaces (H&E, original magnification ×2).

In this case, 2 distinct neoplasms (spiradenoma and trichoepithelioma) are apparent, side by side, with an intervening hair follicle (Figure 1). Trichoepitheliomas, also known as cribriform trichoblastomas,⁵ are characterized by lobules of basaloid cells resembling basal cell carcinoma surrounded by a fibroblast-rich stroma. They often contain fingerlike projections and adopt a cribriform morphology within the tumor lobules (Figure 2B).⁴ Numerous horn cysts may be present, but their absence does not preclude the diagnosis. Mucin may be present within the cribriform tumor islands (Figure 2B) but not in the stroma. Characteristically, trichoepitheliomas are distinctly negative for CK7 (Figure 3), and unlike spiradenomas, they lack a myoepithelial component.⁶ This staining pattern in combination with the tumor’s proximity to an adjacent hair follicle makes a diagnosis of trichoepithelioma and spiradenoma collision tumor most likely and supports a clinical suspicion for Brooke-Spiegler syndrome.

Figure 2. Spiradenomas may demonstrate a trabecular architecture, and on close inspection 2 cell types—paler cells with more cytoplasm and darker cells with less cytoplasm—are distinguishable. Lymphocytes are scattered within the tumor nodules and/or stroma (A)(H&E, original magnification ×100).The individual lobules within a trichoepithelioma can adopt a cribriform morphology, and mucin may be present within the cystic spaces (B)(H&E, original magnification ×90).

Although spiradenomas sometimes contain cystic cavities (microcystic change), they typically are filled with finely granular eosinophilic material, not mucin, that is diastase resistant and periodic acid–Schiff positive (Figure 4).⁷ Spiradenomas classically stain positive with CK7 (Figure 3), epithelial membrane antigen, and carcinoembryonic antigen, and have a substantial myoepithelial component, as evidenced by the myoepithelial component staining with p63, S-100, and smooth muscle actin (SMA).^7-9 The distinct lack of staining with CK7 and SMA in the tumor on the left in Figure 3 confirms that these tumors are of different lineage, rather than representing cystic change within a spiradenoma.

Figure 3. Positive staining with CK7 can be noted in the spiradenoma (right) and negative staining is noted in the trichoepithelioma (left)(original magnification ×3).

Figure 4. Cystic cavities within a spiradenoma are filled with finely granular eosinophilic material, not mucin, that is diastase resistant and periodic acid–Schiff positive (H&E, original magnification ×30).

Adenoid cystic carcinoma is a rare neoplasm that may occur in a primary cutaneous form, as a direct extension from an underlying salivary gland neoplasm, or rarely as a focal pattern within spiradenomas occurring both sporadically or in the context of Brooke-Spiegler syndrome.^2,7 The tumor is composed of variably sized cribriform islands of basaloid to pink cells concentrically arranged around glandlike spaces filled with mucin (Figure 5A). In contrast to trichoepithelioma, ACC occurs in the mid to deep dermis, often extending into subcutaneous fat with an infiltrative border, and is not often found in close proximity to hair follicles.⁷ Characteristically, hyaline basement membrane–like material that is periodic acid–Schiff positive is found between the tumor cells and also surrounding the individual lobules. Immunohistochemically, ACC has a myoepithelial component that stains positive with SMA, S-100, and p63; additionally, the tumor cells express low- and high-molecular-weight keratin and demonstrate variable epithelial membrane antigen positivity.¹⁰ In the current case, the superficial location, close association with a hair follicle, and lack of staining with both CK7 (Figure 3) and SMA (not shown) make ACC arising within a spiradenoma a less likely diagnosis.

Cylindromas are composed of basaloid islands interconnected in a jigsaw puzzle configuration (Figure 5B).⁴ Similar to spiradenomas, they also are composed of 2 cell populations. Characteristically, the tumor islands are outlined by a hyalinized eosinophilic basement membrane. Hyalinized droplets of basement membrane zone material also may be noted in the islands. Unlike spiradenomas, they lack both intratumoral lymphocytes and a trabecular growth pattern. Although spiradenocylindromas (cylindroma and spiradenoma collision tumors) are perhaps the most common collision tumor associated with Brooke-Spiegler syndrome, there is no evidence suggesting the presence of a cylindroma in the current case.

Figure 5. Adenoid cystic carcinoma is composed of variably sized cribriform islands of basaloid to pink cells concentrically arranged around glandlike spaces filled with mucin (A)(H&E, original magnification ×20). Cylindromas are composed of basaloid islands interconnected in a jigsaw puzzle configuration. Characteristically, the tumor islands are outlined by a hyalinized eosinophilic basement membrane (B) (H&E, original magnification ×100).

Primary cutaneous mucinous carcinoma is a rare neoplasm with a predilection for the eyelids; lesions occurring outside of this facial distribution, particularly of the breast, warrant a workup for metastatic disease.⁷ It typically occurs in the deeper dermis with involvement of the subcutaneous fat and is characterized by delicate fibrous septa enveloping large lakes of mucin, which contain islands of tumor cells (Figure 6). It has not been reported in association with spiradenomas. In addition, the tumor cells typically are CK7 positive.

Figure 6. Mucinous carcinoma is characterized by delicate fibrous septa enclosing large lakes of mucin containing islands of tumor cells (H&E, original magnification ×20).

The coexistence of more than one cutaneous adnexal neoplasm in a single biopsy specimen is unusual and is most frequently recognized in the context of a nevus sebaceous or Brooke-Spiegler syndrome, an autosomal-dominant inherited disease characterized by cutaneous adnexal neoplasms, most commonly cylindromas and trichoepitheliomas.^1-3 Brooke-Spiegler syndrome is caused by germline mutations in the cylindromatosis gene, CYLD, located on band 16q12; it functions as a tumor suppressor gene and has regulatory roles in development, immunity, and inflammation.¹ Weyers et al³ first recognized the tendency for adnexal collision tumors to present in patients with Brooke-Spiegler syndrome; they reported a patient with Brooke-Spiegler syndrome with spiradenomas found in the immediate vicinity of trichoepitheliomas and in continuity with hair follicles.

Spiradenomas are composed of large, sharply demarcated, rounded nodules of basaloid cells with little cytoplasm (Figure 1).⁴ The basaloid nodules may demonstrate a trabecular architecture, and on close inspection 2 cell types—paler cells with more cytoplasm and darker cells with less cytoplasm—are distinguishable (Figure 2A). Lymphocytes often are scattered within the tumor nodules and/or stroma. In Brooke-Spiegler syndrome, collision tumors containing a spiradenomatous component in collision with trichoepithelioma are not uncommon.¹ Spiradenomas in Brooke-Spiegler syndrome have been reported to contain sebaceous differentiation or foci with an adenoid cystic carcinoma (ACC)–like pattern and are known to occur as hybrid lesions of spiradenoma and cylindroma or trichoepithelioma (as in this case).

Figure 1. Two distinct neoplasms are apparent, side by side, with an intervening hair follicle. The spirade-noma (right) is a large, sharply demarcated, rounded nodule of basaloid cells containing little cytoplasm. The trichoepithelioma (left) is composed of lobules of basaloid cells with a cribriform architecture, surrounded by a fibroblast-rich stroma. Mucin is apparent within the cystic spaces (H&E, original magnification ×2).

In this case, 2 distinct neoplasms (spiradenoma and trichoepithelioma) are apparent, side by side, with an intervening hair follicle (Figure 1). Trichoepitheliomas, also known as cribriform trichoblastomas,⁵ are characterized by lobules of basaloid cells resembling basal cell carcinoma surrounded by a fibroblast-rich stroma. They often contain fingerlike projections and adopt a cribriform morphology within the tumor lobules (Figure 2B).⁴ Numerous horn cysts may be present, but their absence does not preclude the diagnosis. Mucin may be present within the cribriform tumor islands (Figure 2B) but not in the stroma. Characteristically, trichoepitheliomas are distinctly negative for CK7 (Figure 3), and unlike spiradenomas, they lack a myoepithelial component.⁶ This staining pattern in combination with the tumor’s proximity to an adjacent hair follicle makes a diagnosis of trichoepithelioma and spiradenoma collision tumor most likely and supports a clinical suspicion for Brooke-Spiegler syndrome.

Figure 2. Spiradenomas may demonstrate a trabecular architecture, and on close inspection 2 cell types—paler cells with more cytoplasm and darker cells with less cytoplasm—are distinguishable. Lymphocytes are scattered within the tumor nodules and/or stroma (A)(H&E, original magnification ×100).The individual lobules within a trichoepithelioma can adopt a cribriform morphology, and mucin may be present within the cystic spaces (B)(H&E, original magnification ×90).

Although spiradenomas sometimes contain cystic cavities (microcystic change), they typically are filled with finely granular eosinophilic material, not mucin, that is diastase resistant and periodic acid–Schiff positive (Figure 4).⁷ Spiradenomas classically stain positive with CK7 (Figure 3), epithelial membrane antigen, and carcinoembryonic antigen, and have a substantial myoepithelial component, as evidenced by the myoepithelial component staining with p63, S-100, and smooth muscle actin (SMA).^7-9 The distinct lack of staining with CK7 and SMA in the tumor on the left in Figure 3 confirms that these tumors are of different lineage, rather than representing cystic change within a spiradenoma.

Figure 3. Positive staining with CK7 can be noted in the spiradenoma (right) and negative staining is noted in the trichoepithelioma (left)(original magnification ×3).

Figure 4. Cystic cavities within a spiradenoma are filled with finely granular eosinophilic material, not mucin, that is diastase resistant and periodic acid–Schiff positive (H&E, original magnification ×30).

Adenoid cystic carcinoma is a rare neoplasm that may occur in a primary cutaneous form, as a direct extension from an underlying salivary gland neoplasm, or rarely as a focal pattern within spiradenomas occurring both sporadically or in the context of Brooke-Spiegler syndrome.^2,7 The tumor is composed of variably sized cribriform islands of basaloid to pink cells concentrically arranged around glandlike spaces filled with mucin (Figure 5A). In contrast to trichoepithelioma, ACC occurs in the mid to deep dermis, often extending into subcutaneous fat with an infiltrative border, and is not often found in close proximity to hair follicles.⁷ Characteristically, hyaline basement membrane–like material that is periodic acid–Schiff positive is found between the tumor cells and also surrounding the individual lobules. Immunohistochemically, ACC has a myoepithelial component that stains positive with SMA, S-100, and p63; additionally, the tumor cells express low- and high-molecular-weight keratin and demonstrate variable epithelial membrane antigen positivity.¹⁰ In the current case, the superficial location, close association with a hair follicle, and lack of staining with both CK7 (Figure 3) and SMA (not shown) make ACC arising within a spiradenoma a less likely diagnosis.

Cylindromas are composed of basaloid islands interconnected in a jigsaw puzzle configuration (Figure 5B).⁴ Similar to spiradenomas, they also are composed of 2 cell populations. Characteristically, the tumor islands are outlined by a hyalinized eosinophilic basement membrane. Hyalinized droplets of basement membrane zone material also may be noted in the islands. Unlike spiradenomas, they lack both intratumoral lymphocytes and a trabecular growth pattern. Although spiradenocylindromas (cylindroma and spiradenoma collision tumors) are perhaps the most common collision tumor associated with Brooke-Spiegler syndrome, there is no evidence suggesting the presence of a cylindroma in the current case.

Figure 5. Adenoid cystic carcinoma is composed of variably sized cribriform islands of basaloid to pink cells concentrically arranged around glandlike spaces filled with mucin (A)(H&E, original magnification ×20). Cylindromas are composed of basaloid islands interconnected in a jigsaw puzzle configuration. Characteristically, the tumor islands are outlined by a hyalinized eosinophilic basement membrane (B) (H&E, original magnification ×100).

Primary cutaneous mucinous carcinoma is a rare neoplasm with a predilection for the eyelids; lesions occurring outside of this facial distribution, particularly of the breast, warrant a workup for metastatic disease.⁷ It typically occurs in the deeper dermis with involvement of the subcutaneous fat and is characterized by delicate fibrous septa enveloping large lakes of mucin, which contain islands of tumor cells (Figure 6). It has not been reported in association with spiradenomas. In addition, the tumor cells typically are CK7 positive.

Figure 6. Mucinous carcinoma is characterized by delicate fibrous septa enclosing large lakes of mucin containing islands of tumor cells (H&E, original magnification ×20).

The coexistence of more than one cutaneous adnexal neoplasm in a single biopsy specimen is unusual and is most frequently recognized in the context of a nevus sebaceous or Brooke-Spiegler syndrome, an autosomal-dominant inherited disease characterized by cutaneous adnexal neoplasms, most commonly cylindromas and trichoepitheliomas.^1-3 Brooke-Spiegler syndrome is caused by germline mutations in the cylindromatosis gene, CYLD, located on band 16q12; it functions as a tumor suppressor gene and has regulatory roles in development, immunity, and inflammation.¹ Weyers et al³ first recognized the tendency for adnexal collision tumors to present in patients with Brooke-Spiegler syndrome; they reported a patient with Brooke-Spiegler syndrome with spiradenomas found in the immediate vicinity of trichoepitheliomas and in continuity with hair follicles.

Spiradenomas are composed of large, sharply demarcated, rounded nodules of basaloid cells with little cytoplasm (Figure 1).⁴ The basaloid nodules may demonstrate a trabecular architecture, and on close inspection 2 cell types—paler cells with more cytoplasm and darker cells with less cytoplasm—are distinguishable (Figure 2A). Lymphocytes often are scattered within the tumor nodules and/or stroma. In Brooke-Spiegler syndrome, collision tumors containing a spiradenomatous component in collision with trichoepithelioma are not uncommon.¹ Spiradenomas in Brooke-Spiegler syndrome have been reported to contain sebaceous differentiation or foci with an adenoid cystic carcinoma (ACC)–like pattern and are known to occur as hybrid lesions of spiradenoma and cylindroma or trichoepithelioma (as in this case).

Figure 1. Two distinct neoplasms are apparent, side by side, with an intervening hair follicle. The spirade-noma (right) is a large, sharply demarcated, rounded nodule of basaloid cells containing little cytoplasm. The trichoepithelioma (left) is composed of lobules of basaloid cells with a cribriform architecture, surrounded by a fibroblast-rich stroma. Mucin is apparent within the cystic spaces (H&E, original magnification ×2).

In this case, 2 distinct neoplasms (spiradenoma and trichoepithelioma) are apparent, side by side, with an intervening hair follicle (Figure 1). Trichoepitheliomas, also known as cribriform trichoblastomas,⁵ are characterized by lobules of basaloid cells resembling basal cell carcinoma surrounded by a fibroblast-rich stroma. They often contain fingerlike projections and adopt a cribriform morphology within the tumor lobules (Figure 2B).⁴ Numerous horn cysts may be present, but their absence does not preclude the diagnosis. Mucin may be present within the cribriform tumor islands (Figure 2B) but not in the stroma. Characteristically, trichoepitheliomas are distinctly negative for CK7 (Figure 3), and unlike spiradenomas, they lack a myoepithelial component.⁶ This staining pattern in combination with the tumor’s proximity to an adjacent hair follicle makes a diagnosis of trichoepithelioma and spiradenoma collision tumor most likely and supports a clinical suspicion for Brooke-Spiegler syndrome.

Figure 2. Spiradenomas may demonstrate a trabecular architecture, and on close inspection 2 cell types—paler cells with more cytoplasm and darker cells with less cytoplasm—are distinguishable. Lymphocytes are scattered within the tumor nodules and/or stroma (A)(H&E, original magnification ×100).The individual lobules within a trichoepithelioma can adopt a cribriform morphology, and mucin may be present within the cystic spaces (B)(H&E, original magnification ×90).

Although spiradenomas sometimes contain cystic cavities (microcystic change), they typically are filled with finely granular eosinophilic material, not mucin, that is diastase resistant and periodic acid–Schiff positive (Figure 4).⁷ Spiradenomas classically stain positive with CK7 (Figure 3), epithelial membrane antigen, and carcinoembryonic antigen, and have a substantial myoepithelial component, as evidenced by the myoepithelial component staining with p63, S-100, and smooth muscle actin (SMA).^7-9 The distinct lack of staining with CK7 and SMA in the tumor on the left in Figure 3 confirms that these tumors are of different lineage, rather than representing cystic change within a spiradenoma.

Figure 3. Positive staining with CK7 can be noted in the spiradenoma (right) and negative staining is noted in the trichoepithelioma (left)(original magnification ×3).

Figure 4. Cystic cavities within a spiradenoma are filled with finely granular eosinophilic material, not mucin, that is diastase resistant and periodic acid–Schiff positive (H&E, original magnification ×30).

Adenoid cystic carcinoma is a rare neoplasm that may occur in a primary cutaneous form, as a direct extension from an underlying salivary gland neoplasm, or rarely as a focal pattern within spiradenomas occurring both sporadically or in the context of Brooke-Spiegler syndrome.^2,7 The tumor is composed of variably sized cribriform islands of basaloid to pink cells concentrically arranged around glandlike spaces filled with mucin (Figure 5A). In contrast to trichoepithelioma, ACC occurs in the mid to deep dermis, often extending into subcutaneous fat with an infiltrative border, and is not often found in close proximity to hair follicles.⁷ Characteristically, hyaline basement membrane–like material that is periodic acid–Schiff positive is found between the tumor cells and also surrounding the individual lobules. Immunohistochemically, ACC has a myoepithelial component that stains positive with SMA, S-100, and p63; additionally, the tumor cells express low- and high-molecular-weight keratin and demonstrate variable epithelial membrane antigen positivity.¹⁰ In the current case, the superficial location, close association with a hair follicle, and lack of staining with both CK7 (Figure 3) and SMA (not shown) make ACC arising within a spiradenoma a less likely diagnosis.

Cylindromas are composed of basaloid islands interconnected in a jigsaw puzzle configuration (Figure 5B).⁴ Similar to spiradenomas, they also are composed of 2 cell populations. Characteristically, the tumor islands are outlined by a hyalinized eosinophilic basement membrane. Hyalinized droplets of basement membrane zone material also may be noted in the islands. Unlike spiradenomas, they lack both intratumoral lymphocytes and a trabecular growth pattern. Although spiradenocylindromas (cylindroma and spiradenoma collision tumors) are perhaps the most common collision tumor associated with Brooke-Spiegler syndrome, there is no evidence suggesting the presence of a cylindroma in the current case.

Figure 5. Adenoid cystic carcinoma is composed of variably sized cribriform islands of basaloid to pink cells concentrically arranged around glandlike spaces filled with mucin (A)(H&E, original magnification ×20). Cylindromas are composed of basaloid islands interconnected in a jigsaw puzzle configuration. Characteristically, the tumor islands are outlined by a hyalinized eosinophilic basement membrane (B) (H&E, original magnification ×100).

Primary cutaneous mucinous carcinoma is a rare neoplasm with a predilection for the eyelids; lesions occurring outside of this facial distribution, particularly of the breast, warrant a workup for metastatic disease.⁷ It typically occurs in the deeper dermis with involvement of the subcutaneous fat and is characterized by delicate fibrous septa enveloping large lakes of mucin, which contain islands of tumor cells (Figure 6). It has not been reported in association with spiradenomas. In addition, the tumor cells typically are CK7 positive.

Figure 6. Mucinous carcinoma is characterized by delicate fibrous septa enclosing large lakes of mucin containing islands of tumor cells (H&E, original magnification ×20).