Cutis

To the Editor:

A 55-year-old man presented with hyperpigmented brown macules on the lips, hands, and fingertips of 6 years’ duration. The spots were persistent, asymptomatic, and had not changed in size. The patient denied a history of alopecia or dystrophic nails. He also denied a family history of similar skin findings. He had no personal history of cancer and a colonoscopy performed 5 years prior revealed no notable abnormalities. His medications included amlodipine and hydrocodone-acetaminophen. His mother died of “abdominal bleeding” at 74 years of age and his father died of a brain tumor at 64 years of age. Physical examination demonstrated numerous well-defined, dark brown macules of variable size distributed on the lower and upper mucosal lips (Figure 1A), buccal mucosa, hard palate, and gingiva, as well as the dorsal aspect of the fingers (Figure 1B) and volar aspect of the fingertips (Figure 1C).

A shave biopsy of a dark brown macule from the lower lip (Figure 2) was performed. Histopathologic examination revealed pigmentation of the basal layer of the epidermis with pigment-laden cells in the dermis immediately deep to the surface epithelium. Immunoperoxidase stains showed a normal number and distribution of melanocytes.

A diagnosis of Laugier-Hunziker syndrome (LHS) was made given the age of onset; distribution of pigmentation; and lack of pathologic colonoscopic findings, personal history of cancer, or gastrointestinal tract symptoms.

Benign hyperpigmentation of the lips and fingers has been reported.¹ The average age of onset of LHS is 52 years, and it typically is diagnosed in white adults.^1,2 In LHS, pigmentation is most commonly distributed on the lips, especially the lower lips and oral mucosa.² Pigmentation of the nails in the form of longitudinal melanonychia is present in approximately half of cases.^2,3 There also may be pigmentation of the neck; thorax; abdomen; and acral surfaces, especially the fingertips.^1-3 Rarely, pigmented macules can occur on the genitalia or sclera.^1,2 Unlike Peutz-Jeghers syndrome, the diagnosis of LHS does not result from a germline mutation and carries no risk of gastrointestinal polyposis or internal malignancy.^3,4 The histopathology of a pigmented macule of LHS shows a normal number and morphology of melanocytes. Epidermal basement membrane pigmentation is common, with pigment-laden macrophages evident in the papillary dermis.³

RELATED ARTICLE: Asymptomatic Lower Lip Hyperpigmentation From Laugier-Hunziker Syndrome

The differential diagnosis of multiple lentigines is broad and includes Peutz-Jeghers syndrome; LEOPARD (lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonary stenosis, abnormalities of genitalia, retardation of growth, deafness) syndrome; Carney complexes, including LAMB (lentigines, atrial myxoma, mucocutaneous myxoma, blue nevi) and NAME (nevi, atrial myxoma, myxoid neurofibroma, ephelide) syndromes⁵; primary adrenocortical insufficiency (Addison disease); and idiopathic melanoplakia^.2 Peutz-Jeghers syndrome, an autosomal-dominant syndrome with mucocutaneous lentigines, has a similar clinical appearance to LHS; therefore, it is necessary to exclude this diagnosis due to its association with intestinal hamartomatous polyps and internal malignancies (Table).^3,6,7

Peutz-Jeghers syndrome is characterized by mucocutaneous hyperpigmentation and intestinal hamartomatous polyposis and is associated with internal malignancies of the colon, breast, pancreas, stomach, small intestines, ovaries, lung, and Sertoli cells in men.^6,7 Associated gastrointestinal tract malignancies in descending order of frequency are colon (39%), pancreatic (36%), gastric (29%), and small intestine (13%).¹ It is caused by a germ line mutation of the serine/threonine kinase 11 gene, STK11. Although the appearance and distribution of the mucocutaneous lentigines is similar to individuals with LHS, by contrast the lentiginosis in individuals with Peutz-Jeghers syndrome is present from birth or develops during infancy.⁶ Aggressive cancer screening guidelines aid in early detection and begin at 8 years of age with a baseline colonoscopy and esophagogastroduodenoscopy; future screening is dictated by the presence or absence of polyps. If no polyps are detected at 8 years of age, a colonoscopy and esophagogastroduodenoscopy are repeated at 18 years of age and then every 3 years until 50 years of age.⁸

In an adult patient, the diagnosis of LHS can be made clinically and a correct diagnosis prevents frequent and unpleasant gastrointestinal tract cancer screening examinations. Lampe et al² described a man with LHS who was incorrectly diagnosed with Peutz-Jeghers syndrome and experienced a colonic perforation as a complication of a screening colonoscopy. Their case report underscores the importance of making the correct diagnosis of LHS to avoid undertaking unnecessary aggressive cancer screening regimens.²

Although LHS is a benign condition that does not require treatment, Q-switched alexandrite or erbium:YAG laser therapy has been shown to improve the pigmentary findings associated with LHS.^9,10 It has been suggested that LHS should be renamed Laugier-Hunziker pigmentation² or mucocutaneous lentiginosis of Laugier and Hunziker¹ to differentiate LHS as simply a disorder of pigmentation rather than a potentially morbid genetic defect, as in Peutz-Jeghers syndrome.

To the Editor:

A 55-year-old man presented with hyperpigmented brown macules on the lips, hands, and fingertips of 6 years’ duration. The spots were persistent, asymptomatic, and had not changed in size. The patient denied a history of alopecia or dystrophic nails. He also denied a family history of similar skin findings. He had no personal history of cancer and a colonoscopy performed 5 years prior revealed no notable abnormalities. His medications included amlodipine and hydrocodone-acetaminophen. His mother died of “abdominal bleeding” at 74 years of age and his father died of a brain tumor at 64 years of age. Physical examination demonstrated numerous well-defined, dark brown macules of variable size distributed on the lower and upper mucosal lips (Figure 1A), buccal mucosa, hard palate, and gingiva, as well as the dorsal aspect of the fingers (Figure 1B) and volar aspect of the fingertips (Figure 1C).

A shave biopsy of a dark brown macule from the lower lip (Figure 2) was performed. Histopathologic examination revealed pigmentation of the basal layer of the epidermis with pigment-laden cells in the dermis immediately deep to the surface epithelium. Immunoperoxidase stains showed a normal number and distribution of melanocytes.

A diagnosis of Laugier-Hunziker syndrome (LHS) was made given the age of onset; distribution of pigmentation; and lack of pathologic colonoscopic findings, personal history of cancer, or gastrointestinal tract symptoms.

Benign hyperpigmentation of the lips and fingers has been reported.¹ The average age of onset of LHS is 52 years, and it typically is diagnosed in white adults.^1,2 In LHS, pigmentation is most commonly distributed on the lips, especially the lower lips and oral mucosa.² Pigmentation of the nails in the form of longitudinal melanonychia is present in approximately half of cases.^2,3 There also may be pigmentation of the neck; thorax; abdomen; and acral surfaces, especially the fingertips.^1-3 Rarely, pigmented macules can occur on the genitalia or sclera.^1,2 Unlike Peutz-Jeghers syndrome, the diagnosis of LHS does not result from a germline mutation and carries no risk of gastrointestinal polyposis or internal malignancy.^3,4 The histopathology of a pigmented macule of LHS shows a normal number and morphology of melanocytes. Epidermal basement membrane pigmentation is common, with pigment-laden macrophages evident in the papillary dermis.³

RELATED ARTICLE: Asymptomatic Lower Lip Hyperpigmentation From Laugier-Hunziker Syndrome

The differential diagnosis of multiple lentigines is broad and includes Peutz-Jeghers syndrome; LEOPARD (lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonary stenosis, abnormalities of genitalia, retardation of growth, deafness) syndrome; Carney complexes, including LAMB (lentigines, atrial myxoma, mucocutaneous myxoma, blue nevi) and NAME (nevi, atrial myxoma, myxoid neurofibroma, ephelide) syndromes⁵; primary adrenocortical insufficiency (Addison disease); and idiopathic melanoplakia^.2 Peutz-Jeghers syndrome, an autosomal-dominant syndrome with mucocutaneous lentigines, has a similar clinical appearance to LHS; therefore, it is necessary to exclude this diagnosis due to its association with intestinal hamartomatous polyps and internal malignancies (Table).^3,6,7

Peutz-Jeghers syndrome is characterized by mucocutaneous hyperpigmentation and intestinal hamartomatous polyposis and is associated with internal malignancies of the colon, breast, pancreas, stomach, small intestines, ovaries, lung, and Sertoli cells in men.^6,7 Associated gastrointestinal tract malignancies in descending order of frequency are colon (39%), pancreatic (36%), gastric (29%), and small intestine (13%).¹ It is caused by a germ line mutation of the serine/threonine kinase 11 gene, STK11. Although the appearance and distribution of the mucocutaneous lentigines is similar to individuals with LHS, by contrast the lentiginosis in individuals with Peutz-Jeghers syndrome is present from birth or develops during infancy.⁶ Aggressive cancer screening guidelines aid in early detection and begin at 8 years of age with a baseline colonoscopy and esophagogastroduodenoscopy; future screening is dictated by the presence or absence of polyps. If no polyps are detected at 8 years of age, a colonoscopy and esophagogastroduodenoscopy are repeated at 18 years of age and then every 3 years until 50 years of age.⁸

In an adult patient, the diagnosis of LHS can be made clinically and a correct diagnosis prevents frequent and unpleasant gastrointestinal tract cancer screening examinations. Lampe et al² described a man with LHS who was incorrectly diagnosed with Peutz-Jeghers syndrome and experienced a colonic perforation as a complication of a screening colonoscopy. Their case report underscores the importance of making the correct diagnosis of LHS to avoid undertaking unnecessary aggressive cancer screening regimens.²

Although LHS is a benign condition that does not require treatment, Q-switched alexandrite or erbium:YAG laser therapy has been shown to improve the pigmentary findings associated with LHS.^9,10 It has been suggested that LHS should be renamed Laugier-Hunziker pigmentation² or mucocutaneous lentiginosis of Laugier and Hunziker¹ to differentiate LHS as simply a disorder of pigmentation rather than a potentially morbid genetic defect, as in Peutz-Jeghers syndrome.

To the Editor:

A 55-year-old man presented with hyperpigmented brown macules on the lips, hands, and fingertips of 6 years’ duration. The spots were persistent, asymptomatic, and had not changed in size. The patient denied a history of alopecia or dystrophic nails. He also denied a family history of similar skin findings. He had no personal history of cancer and a colonoscopy performed 5 years prior revealed no notable abnormalities. His medications included amlodipine and hydrocodone-acetaminophen. His mother died of “abdominal bleeding” at 74 years of age and his father died of a brain tumor at 64 years of age. Physical examination demonstrated numerous well-defined, dark brown macules of variable size distributed on the lower and upper mucosal lips (Figure 1A), buccal mucosa, hard palate, and gingiva, as well as the dorsal aspect of the fingers (Figure 1B) and volar aspect of the fingertips (Figure 1C).

A shave biopsy of a dark brown macule from the lower lip (Figure 2) was performed. Histopathologic examination revealed pigmentation of the basal layer of the epidermis with pigment-laden cells in the dermis immediately deep to the surface epithelium. Immunoperoxidase stains showed a normal number and distribution of melanocytes.

A diagnosis of Laugier-Hunziker syndrome (LHS) was made given the age of onset; distribution of pigmentation; and lack of pathologic colonoscopic findings, personal history of cancer, or gastrointestinal tract symptoms.

Benign hyperpigmentation of the lips and fingers has been reported.¹ The average age of onset of LHS is 52 years, and it typically is diagnosed in white adults.^1,2 In LHS, pigmentation is most commonly distributed on the lips, especially the lower lips and oral mucosa.² Pigmentation of the nails in the form of longitudinal melanonychia is present in approximately half of cases.^2,3 There also may be pigmentation of the neck; thorax; abdomen; and acral surfaces, especially the fingertips.^1-3 Rarely, pigmented macules can occur on the genitalia or sclera.^1,2 Unlike Peutz-Jeghers syndrome, the diagnosis of LHS does not result from a germline mutation and carries no risk of gastrointestinal polyposis or internal malignancy.^3,4 The histopathology of a pigmented macule of LHS shows a normal number and morphology of melanocytes. Epidermal basement membrane pigmentation is common, with pigment-laden macrophages evident in the papillary dermis.³

RELATED ARTICLE: Asymptomatic Lower Lip Hyperpigmentation From Laugier-Hunziker Syndrome

The differential diagnosis of multiple lentigines is broad and includes Peutz-Jeghers syndrome; LEOPARD (lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonary stenosis, abnormalities of genitalia, retardation of growth, deafness) syndrome; Carney complexes, including LAMB (lentigines, atrial myxoma, mucocutaneous myxoma, blue nevi) and NAME (nevi, atrial myxoma, myxoid neurofibroma, ephelide) syndromes⁵; primary adrenocortical insufficiency (Addison disease); and idiopathic melanoplakia^.2 Peutz-Jeghers syndrome, an autosomal-dominant syndrome with mucocutaneous lentigines, has a similar clinical appearance to LHS; therefore, it is necessary to exclude this diagnosis due to its association with intestinal hamartomatous polyps and internal malignancies (Table).^3,6,7

Peutz-Jeghers syndrome is characterized by mucocutaneous hyperpigmentation and intestinal hamartomatous polyposis and is associated with internal malignancies of the colon, breast, pancreas, stomach, small intestines, ovaries, lung, and Sertoli cells in men.^6,7 Associated gastrointestinal tract malignancies in descending order of frequency are colon (39%), pancreatic (36%), gastric (29%), and small intestine (13%).¹ It is caused by a germ line mutation of the serine/threonine kinase 11 gene, STK11. Although the appearance and distribution of the mucocutaneous lentigines is similar to individuals with LHS, by contrast the lentiginosis in individuals with Peutz-Jeghers syndrome is present from birth or develops during infancy.⁶ Aggressive cancer screening guidelines aid in early detection and begin at 8 years of age with a baseline colonoscopy and esophagogastroduodenoscopy; future screening is dictated by the presence or absence of polyps. If no polyps are detected at 8 years of age, a colonoscopy and esophagogastroduodenoscopy are repeated at 18 years of age and then every 3 years until 50 years of age.⁸

In an adult patient, the diagnosis of LHS can be made clinically and a correct diagnosis prevents frequent and unpleasant gastrointestinal tract cancer screening examinations. Lampe et al² described a man with LHS who was incorrectly diagnosed with Peutz-Jeghers syndrome and experienced a colonic perforation as a complication of a screening colonoscopy. Their case report underscores the importance of making the correct diagnosis of LHS to avoid undertaking unnecessary aggressive cancer screening regimens.²

Although LHS is a benign condition that does not require treatment, Q-switched alexandrite or erbium:YAG laser therapy has been shown to improve the pigmentary findings associated with LHS.^9,10 It has been suggested that LHS should be renamed Laugier-Hunziker pigmentation² or mucocutaneous lentiginosis of Laugier and Hunziker¹ to differentiate LHS as simply a disorder of pigmentation rather than a potentially morbid genetic defect, as in Peutz-Jeghers syndrome.

Atypical fibroxanthoma (AFX) is a low-grade dermal malignancy comprised of atypical spindle cells.¹ Classified as a superficial fibrohistiocytic tumor with intermediate malignant potential, AFX has an incidence of approximately 0.24% worldwide.² The tumor appears mainly on the head and neck in sun-exposed areas but can occur less frequently on the trunk and limbs in non–sun-exposed areas. There is a 70% to 80% predominance in men aged 69 to 77 years, with lesions primarily occurring in sun-exposed areas of the head and neck.³ A median period of 4 months between time of onset and time of diagnosis has been previously established.⁴

When AFX does occur in non–sun-exposed areas, it tends to be in a younger patient population. Clinically, it presents as a rather nondescript, firm, erythematous papule or nodule less than 2 cm in diameter. Atypical fibroxanthoma most often presents asymptomatically, but the tumor may ulcerate and bleed, though pain and pruritus are uncommon.5 Findings are nonspecific, and the diagnosis must be confirmed with biopsy, as it can resemble other common dermatological lesions. The pathogenesis of AFX has been controversial. Two different studies looked at AFX using electron microscopy and concluded that the tumor most closely resembled a myofibroblast,^6,7 which is consistent with current thinking today.

Atypical fibroxanthoma is believed to be associated with p53 mutation and is closely linked with exposure to UV radiation due to its predominance in sun-exposed areas. Other predisposing factors may include prior exposure to UV radiation, history of organ transplantation, immunosuppression, advanced age in men, and xeroderma pigmentosum. The differential diagnosis for AFX encompasses basal cell carcinoma, squamous cell carcinoma, Merkel cell carcinoma, adnexal tumor, and pyogenic granuloma.

Case Report

A 93-year-old man was referred to our clinic for treatment of erosive pustular dermatosis of the scalp with photodynamic therapy (PDT). He had a more than 20-year history of multiple skin lesions including basal cell carcinoma, squamous cell carcinoma, and actinic keratoses (AKs). For one year prior to the current presentation the patient had concerns of pustules, scaling, itching, and scabbing on the scalp. The patient admitted that the pruritus caused him to pick at the scabs on the scalp. He had previously been treated with lactic acid 12% neutralized with ammonium hydroxide, tacrolimus, and halobetasol, all to no avail.

On physical examination, the lesions appeared erosive with crusting and granulation tissue (Figure 1A). The presentation was consistent with erosive pustular dermatosis of the scalp. Biopsy revealed granulation tissue. The patient underwent PDT and prednisone treatment with improvement. Additional biopsies revealed AKs. His condition improved with 2 PDT sessions but never fully cleared. During the PDT sessions, the patient reported intense unilateral headaches without visual changes. The headaches were intermittent and not apparently related to the treatments. He was referred for a temporal artery biopsy and rebiopsy of the remaining lesion on the scalp. The temporal artery biopsy was negative. The lesion that remained was a large nodule on the vertex scalp, and biopsy revealed AFX.

Immunohistochemical marker studies for S-100 and cytokeratin were negative. Invasion into subcutaneous fat was encountered (Figure 2A). Highly atypical spindle cells and mitoses were present (Figure 2B). Neoplastic cells were noted adjacent to nerve (Figure 2C). Excision of the lesion was curative, and his symptoms of pain and erosive pustular dermatosis resolved weeks thereafter (Figure 1B). The area of erosive pustular dermatosis was not excised, but symptoms resolved weeks following excision of the AFX.

Comment

Our case of AFX is unique due to the patient’s atypical presentation of severe pain. Because AFX usually presents asymptomatically, pain is an uncommon symptom. Based on the histologic findings in our case, we suspected that neural involvement of the tumor most likely explained the intense pain that our patient experienced.

The presence of erosive pustular dermatosis of the scalp also is interesting in our case. This elderly man had an extensive history of actinic damage and had reported pustules, scaling, itching, and scabbing of the scalp. It is possible that erosive pustular dermatosis was superimposed over the tumor and could have been the reason that multiple biopsies were needed to eventually arrive at a diagnosis. The coexistence of the 2 entities suggests that the chronic actinic damage played a role in the etiology of both.

Classification
There is a question regarding nomenclature when discussing AFX. Atypical fibroxanthoma has been referred to as a variant of undifferentiated pleomorphic sarcoma, which is a type of soft tissue sarcoma. Atypical fibroxanthoma can be referred to as undifferentiated pleomorphic sarcoma if it is more than 2 cm in diameter, if it involves the fascia or subcutaneous tissue, or if there is evidence of necrosis.³ Atypical fibroxanthoma generally is confined to the head and neck region and usually is less than 2 cm in diameter. In this patient, the presentation was consistent with AFX, as there was evidence of necrosis and invasion into the subcutaneous fat. The fact that the lesion also appeared on the scalp further supported the diagnosis of AFX.

Pathology
Biopsy of AFX typically reveals a spindle cell proliferation that usually arises in the setting of profound actinic damage. The epidermis may or may not be ulcerated, and in most cases, it is seen in close proximity to the overlying epidermis but not arising from it.8 Classic AFX is composed of highly atypical histiocytelike (epithelioid) cells admixed with pleomorphic spindle cells and giant cells, all showing frequent mitoses including atypical ones.9 Several histologic subtypes of AFX have been described, including clear cell, granular cell, pigmented cell, chondroid, osteoid, osteoclastic, and the most common spindle cell subtype.9 Features that indicate potential aggressive behavior include infiltration into the subcutaneous tissue, vascular invasion, and presence of necrosis. A diagnosis of AFX is made by exclusion of other malignant neoplasms with similar morphology, namely spindle cell squamous cell carcinoma, spindle cell melanoma, and leiomyoscarcoma.9 As such, immunohistochemistry plays a critical role in distinguishing these lesions, as they arise as part of the differential diagnosis. A panel of immunohistochemical stains is helpful for diagnosis and commonly includes but is not limited to S-100, Melan-A, smooth muscle actin, desmin, and cytokeratin.

Sampling error is an inherent flaw in any biopsy specimen. The eventual diagnosis of AFX in our case supports the argument for multiple biopsies of an unknown lesion, seeing as the affected area was interpreted as both granulation tissue and AK prior to the eventual diagnosis. Repeat biopsies, especially if a lesion is nonhealing, often can help clinicians arrive at a definitive diagnosis.

Treatment
Different treatment options have been used to manage AFX. Mohs micrographic surgery is most often used because of its tissue-sparing potential, often giving the most cosmetically appealing result. Wide local excision is another surgical technique utilized, generally with fixed margins of at least 1 cm.¹⁰ Radiation at the tumor site is used as a treatment method but most often during cases of reoccurrence. Cryotherapy as well as electrodesiccation and curettage are possible treatment options but are not the standard of care.

Atypical fibroxanthoma (AFX) is a low-grade dermal malignancy comprised of atypical spindle cells.¹ Classified as a superficial fibrohistiocytic tumor with intermediate malignant potential, AFX has an incidence of approximately 0.24% worldwide.² The tumor appears mainly on the head and neck in sun-exposed areas but can occur less frequently on the trunk and limbs in non–sun-exposed areas. There is a 70% to 80% predominance in men aged 69 to 77 years, with lesions primarily occurring in sun-exposed areas of the head and neck.³ A median period of 4 months between time of onset and time of diagnosis has been previously established.⁴

When AFX does occur in non–sun-exposed areas, it tends to be in a younger patient population. Clinically, it presents as a rather nondescript, firm, erythematous papule or nodule less than 2 cm in diameter. Atypical fibroxanthoma most often presents asymptomatically, but the tumor may ulcerate and bleed, though pain and pruritus are uncommon.5 Findings are nonspecific, and the diagnosis must be confirmed with biopsy, as it can resemble other common dermatological lesions. The pathogenesis of AFX has been controversial. Two different studies looked at AFX using electron microscopy and concluded that the tumor most closely resembled a myofibroblast,^6,7 which is consistent with current thinking today.

Atypical fibroxanthoma is believed to be associated with p53 mutation and is closely linked with exposure to UV radiation due to its predominance in sun-exposed areas. Other predisposing factors may include prior exposure to UV radiation, history of organ transplantation, immunosuppression, advanced age in men, and xeroderma pigmentosum. The differential diagnosis for AFX encompasses basal cell carcinoma, squamous cell carcinoma, Merkel cell carcinoma, adnexal tumor, and pyogenic granuloma.

Case Report

A 93-year-old man was referred to our clinic for treatment of erosive pustular dermatosis of the scalp with photodynamic therapy (PDT). He had a more than 20-year history of multiple skin lesions including basal cell carcinoma, squamous cell carcinoma, and actinic keratoses (AKs). For one year prior to the current presentation the patient had concerns of pustules, scaling, itching, and scabbing on the scalp. The patient admitted that the pruritus caused him to pick at the scabs on the scalp. He had previously been treated with lactic acid 12% neutralized with ammonium hydroxide, tacrolimus, and halobetasol, all to no avail.

On physical examination, the lesions appeared erosive with crusting and granulation tissue (Figure 1A). The presentation was consistent with erosive pustular dermatosis of the scalp. Biopsy revealed granulation tissue. The patient underwent PDT and prednisone treatment with improvement. Additional biopsies revealed AKs. His condition improved with 2 PDT sessions but never fully cleared. During the PDT sessions, the patient reported intense unilateral headaches without visual changes. The headaches were intermittent and not apparently related to the treatments. He was referred for a temporal artery biopsy and rebiopsy of the remaining lesion on the scalp. The temporal artery biopsy was negative. The lesion that remained was a large nodule on the vertex scalp, and biopsy revealed AFX.

Immunohistochemical marker studies for S-100 and cytokeratin were negative. Invasion into subcutaneous fat was encountered (Figure 2A). Highly atypical spindle cells and mitoses were present (Figure 2B). Neoplastic cells were noted adjacent to nerve (Figure 2C). Excision of the lesion was curative, and his symptoms of pain and erosive pustular dermatosis resolved weeks thereafter (Figure 1B). The area of erosive pustular dermatosis was not excised, but symptoms resolved weeks following excision of the AFX.

Comment

Our case of AFX is unique due to the patient’s atypical presentation of severe pain. Because AFX usually presents asymptomatically, pain is an uncommon symptom. Based on the histologic findings in our case, we suspected that neural involvement of the tumor most likely explained the intense pain that our patient experienced.

The presence of erosive pustular dermatosis of the scalp also is interesting in our case. This elderly man had an extensive history of actinic damage and had reported pustules, scaling, itching, and scabbing of the scalp. It is possible that erosive pustular dermatosis was superimposed over the tumor and could have been the reason that multiple biopsies were needed to eventually arrive at a diagnosis. The coexistence of the 2 entities suggests that the chronic actinic damage played a role in the etiology of both.

Classification
There is a question regarding nomenclature when discussing AFX. Atypical fibroxanthoma has been referred to as a variant of undifferentiated pleomorphic sarcoma, which is a type of soft tissue sarcoma. Atypical fibroxanthoma can be referred to as undifferentiated pleomorphic sarcoma if it is more than 2 cm in diameter, if it involves the fascia or subcutaneous tissue, or if there is evidence of necrosis.³ Atypical fibroxanthoma generally is confined to the head and neck region and usually is less than 2 cm in diameter. In this patient, the presentation was consistent with AFX, as there was evidence of necrosis and invasion into the subcutaneous fat. The fact that the lesion also appeared on the scalp further supported the diagnosis of AFX.

Pathology
Biopsy of AFX typically reveals a spindle cell proliferation that usually arises in the setting of profound actinic damage. The epidermis may or may not be ulcerated, and in most cases, it is seen in close proximity to the overlying epidermis but not arising from it.8 Classic AFX is composed of highly atypical histiocytelike (epithelioid) cells admixed with pleomorphic spindle cells and giant cells, all showing frequent mitoses including atypical ones.9 Several histologic subtypes of AFX have been described, including clear cell, granular cell, pigmented cell, chondroid, osteoid, osteoclastic, and the most common spindle cell subtype.9 Features that indicate potential aggressive behavior include infiltration into the subcutaneous tissue, vascular invasion, and presence of necrosis. A diagnosis of AFX is made by exclusion of other malignant neoplasms with similar morphology, namely spindle cell squamous cell carcinoma, spindle cell melanoma, and leiomyoscarcoma.9 As such, immunohistochemistry plays a critical role in distinguishing these lesions, as they arise as part of the differential diagnosis. A panel of immunohistochemical stains is helpful for diagnosis and commonly includes but is not limited to S-100, Melan-A, smooth muscle actin, desmin, and cytokeratin.

Sampling error is an inherent flaw in any biopsy specimen. The eventual diagnosis of AFX in our case supports the argument for multiple biopsies of an unknown lesion, seeing as the affected area was interpreted as both granulation tissue and AK prior to the eventual diagnosis. Repeat biopsies, especially if a lesion is nonhealing, often can help clinicians arrive at a definitive diagnosis.

Treatment
Different treatment options have been used to manage AFX. Mohs micrographic surgery is most often used because of its tissue-sparing potential, often giving the most cosmetically appealing result. Wide local excision is another surgical technique utilized, generally with fixed margins of at least 1 cm.¹⁰ Radiation at the tumor site is used as a treatment method but most often during cases of reoccurrence. Cryotherapy as well as electrodesiccation and curettage are possible treatment options but are not the standard of care.

Atypical fibroxanthoma (AFX) is a low-grade dermal malignancy comprised of atypical spindle cells.¹ Classified as a superficial fibrohistiocytic tumor with intermediate malignant potential, AFX has an incidence of approximately 0.24% worldwide.² The tumor appears mainly on the head and neck in sun-exposed areas but can occur less frequently on the trunk and limbs in non–sun-exposed areas. There is a 70% to 80% predominance in men aged 69 to 77 years, with lesions primarily occurring in sun-exposed areas of the head and neck.³ A median period of 4 months between time of onset and time of diagnosis has been previously established.⁴

When AFX does occur in non–sun-exposed areas, it tends to be in a younger patient population. Clinically, it presents as a rather nondescript, firm, erythematous papule or nodule less than 2 cm in diameter. Atypical fibroxanthoma most often presents asymptomatically, but the tumor may ulcerate and bleed, though pain and pruritus are uncommon.5 Findings are nonspecific, and the diagnosis must be confirmed with biopsy, as it can resemble other common dermatological lesions. The pathogenesis of AFX has been controversial. Two different studies looked at AFX using electron microscopy and concluded that the tumor most closely resembled a myofibroblast,^6,7 which is consistent with current thinking today.

Atypical fibroxanthoma is believed to be associated with p53 mutation and is closely linked with exposure to UV radiation due to its predominance in sun-exposed areas. Other predisposing factors may include prior exposure to UV radiation, history of organ transplantation, immunosuppression, advanced age in men, and xeroderma pigmentosum. The differential diagnosis for AFX encompasses basal cell carcinoma, squamous cell carcinoma, Merkel cell carcinoma, adnexal tumor, and pyogenic granuloma.

Case Report

A 93-year-old man was referred to our clinic for treatment of erosive pustular dermatosis of the scalp with photodynamic therapy (PDT). He had a more than 20-year history of multiple skin lesions including basal cell carcinoma, squamous cell carcinoma, and actinic keratoses (AKs). For one year prior to the current presentation the patient had concerns of pustules, scaling, itching, and scabbing on the scalp. The patient admitted that the pruritus caused him to pick at the scabs on the scalp. He had previously been treated with lactic acid 12% neutralized with ammonium hydroxide, tacrolimus, and halobetasol, all to no avail.

On physical examination, the lesions appeared erosive with crusting and granulation tissue (Figure 1A). The presentation was consistent with erosive pustular dermatosis of the scalp. Biopsy revealed granulation tissue. The patient underwent PDT and prednisone treatment with improvement. Additional biopsies revealed AKs. His condition improved with 2 PDT sessions but never fully cleared. During the PDT sessions, the patient reported intense unilateral headaches without visual changes. The headaches were intermittent and not apparently related to the treatments. He was referred for a temporal artery biopsy and rebiopsy of the remaining lesion on the scalp. The temporal artery biopsy was negative. The lesion that remained was a large nodule on the vertex scalp, and biopsy revealed AFX.

Immunohistochemical marker studies for S-100 and cytokeratin were negative. Invasion into subcutaneous fat was encountered (Figure 2A). Highly atypical spindle cells and mitoses were present (Figure 2B). Neoplastic cells were noted adjacent to nerve (Figure 2C). Excision of the lesion was curative, and his symptoms of pain and erosive pustular dermatosis resolved weeks thereafter (Figure 1B). The area of erosive pustular dermatosis was not excised, but symptoms resolved weeks following excision of the AFX.

Comment

Our case of AFX is unique due to the patient’s atypical presentation of severe pain. Because AFX usually presents asymptomatically, pain is an uncommon symptom. Based on the histologic findings in our case, we suspected that neural involvement of the tumor most likely explained the intense pain that our patient experienced.

The presence of erosive pustular dermatosis of the scalp also is interesting in our case. This elderly man had an extensive history of actinic damage and had reported pustules, scaling, itching, and scabbing of the scalp. It is possible that erosive pustular dermatosis was superimposed over the tumor and could have been the reason that multiple biopsies were needed to eventually arrive at a diagnosis. The coexistence of the 2 entities suggests that the chronic actinic damage played a role in the etiology of both.

Classification
There is a question regarding nomenclature when discussing AFX. Atypical fibroxanthoma has been referred to as a variant of undifferentiated pleomorphic sarcoma, which is a type of soft tissue sarcoma. Atypical fibroxanthoma can be referred to as undifferentiated pleomorphic sarcoma if it is more than 2 cm in diameter, if it involves the fascia or subcutaneous tissue, or if there is evidence of necrosis.³ Atypical fibroxanthoma generally is confined to the head and neck region and usually is less than 2 cm in diameter. In this patient, the presentation was consistent with AFX, as there was evidence of necrosis and invasion into the subcutaneous fat. The fact that the lesion also appeared on the scalp further supported the diagnosis of AFX.

Pathology
Biopsy of AFX typically reveals a spindle cell proliferation that usually arises in the setting of profound actinic damage. The epidermis may or may not be ulcerated, and in most cases, it is seen in close proximity to the overlying epidermis but not arising from it.8 Classic AFX is composed of highly atypical histiocytelike (epithelioid) cells admixed with pleomorphic spindle cells and giant cells, all showing frequent mitoses including atypical ones.9 Several histologic subtypes of AFX have been described, including clear cell, granular cell, pigmented cell, chondroid, osteoid, osteoclastic, and the most common spindle cell subtype.9 Features that indicate potential aggressive behavior include infiltration into the subcutaneous tissue, vascular invasion, and presence of necrosis. A diagnosis of AFX is made by exclusion of other malignant neoplasms with similar morphology, namely spindle cell squamous cell carcinoma, spindle cell melanoma, and leiomyoscarcoma.9 As such, immunohistochemistry plays a critical role in distinguishing these lesions, as they arise as part of the differential diagnosis. A panel of immunohistochemical stains is helpful for diagnosis and commonly includes but is not limited to S-100, Melan-A, smooth muscle actin, desmin, and cytokeratin.

Sampling error is an inherent flaw in any biopsy specimen. The eventual diagnosis of AFX in our case supports the argument for multiple biopsies of an unknown lesion, seeing as the affected area was interpreted as both granulation tissue and AK prior to the eventual diagnosis. Repeat biopsies, especially if a lesion is nonhealing, often can help clinicians arrive at a definitive diagnosis.

Treatment
Different treatment options have been used to manage AFX. Mohs micrographic surgery is most often used because of its tissue-sparing potential, often giving the most cosmetically appealing result. Wide local excision is another surgical technique utilized, generally with fixed margins of at least 1 cm.¹⁰ Radiation at the tumor site is used as a treatment method but most often during cases of reoccurrence. Cryotherapy as well as electrodesiccation and curettage are possible treatment options but are not the standard of care.