Timothy Patton, DO

To the Editor:

Eosinophilic pustular folliculitis (EPF) is a noninfectious dermatosis that typically manifests as recurrent follicular papulopustules that generally affect the face and occasionally the trunk and arms. There are several subtypes of EPF: classic EPF (Ofuji disease), infancy-associated EPF, and immunosuppression-associated EPF.^1,2 We report a rare case of EPF in the setting of untreated chronic lymphocytic leukemia (CLL), a subtype of immunosuppression­-associated EPF that has been associated with hematologic malignancy EPF (HM-EPF).^3-5

A 69-year-old woman presented with diffusely scattered, pruritic, erythematous, erosive lesions on the back, arms, legs, and forehead (Figure 1) of 4 months’ duration, as well as an ulcerative lesion on the left third toe due to a suspected insect bite. She had a history of untreated CLL that was diagnosed 2 years prior. The patient was empirically started on clindamycin for presumed infection of the toe. A punch biopsy of the left wrist revealed superficial and deep dermal perivascular and interstitial inflammatory infiltrates composed of lymphocytes, histiocytes, and numerous eosinophils in association with edema and necrosis. Histopathology was overall most consistent with an exuberant arthropod reaction; however, at 2-week follow-up, the patient reported that the pustular lesions improved upon starting antibiotics, which raised concerns for a bacterial process. The patient initially was continued on clindamycin given subjective improvement but was later switched to daptomycin, as she developed clindamycin-resistant methicillin-resistant Staphylococcus aureus osteomyelitis from the necrotic toe.

A month later, the patient returned with new papules and pustules on the arms and trunk. A repeat biopsy showed notable dermal collections comprised predominantly of neutrophils and eosinophils as well as involvement of follicular structures by dense inflammation (Figure 2). Immunohistochemistry demonstrated a predominant population of small CD3⁺ T cells, which raised concern for cutaneous T-cell lymphoma. However, retention of CD5 expression made this less likely. Few scattered CD20⁺ B cells with limited CD23 reactivity and without CD5 co-expression were detected, which ruled out cutaneous involvement of the patient’s CLL. Bacterial culture and Grocott methenamine-silver, Gram, acid-fast bacilli, and periodic acid-Schiff stains were negative. Polymerase chain reaction testing for varicella-zoster virus and herpes simplex virus also were negative. Thus, a diagnosis of EPF secondary to CLL was favored, as an infectious process also was unlikely. The patient was started on triamcinolone cream 0.1% with gradual improvement.

Cases of HM-EPF predominantly have been reported in patients who have undergone chemotherapy, bone marrow transplantation, or hematopoietic stem cell transplantation. Furthermore, a vast majority of these cases have been reported in older males.^3-16 In a retrospective study of more than 750 patients with established CLL, Agnew et al⁷ identified 125 different skin complications in 40 patients. Of this subset, only a small number (2/40) were associated with eosinophilic folliculitis, with 1 case noted in a middle-aged woman with a history of CLL treatment.⁷ Moreover, Motaparthi et al⁴ reported 3 additional cases of HM-EPF, with all patients identified as middle-aged men who were treated with chemotherapy for underlying CLL. Our patient represents a case of EPF in the context of untreated CLL in a woman.

Although topical corticosteroids remain the first-line treatment for EPF, a survey study conducted across 67 hospitals in Japan indicated that antibiotics were moderately or highly effective in 79% of EPF patients (n=143).¹⁷ This association may explain the subjective improvement reported by our patient upon starting clindamycin. Furthermore, in HIV-associated EPF, high-dose cetirizine, itraconazole, and metronidazole have been successful when topical therapies have failed.¹⁸ Although the precise pathogenesis of EPF is unknown, histopathologic features, clinical appearance, and identification of the accurate EPF subtype can still prove valuable in informing empiric treatment strategies. Consequently, the initial histopathologic diagnosis of an arthropod bite reaction in our patient highlights the importance of clinical correlation and additional ancillary studies in the determination of EPF vs other inflammatory dermatoses that manifest microscopically with lymphocytic infiltrates, prominent eosinophils, and follicular involvement.⁴ The histopathologic features of EPF demonstrate considerable overlap with eosinophilic dermatosis of hematologic malignancy (also known as eosinophilic dermatosis of myeloproliferative disease). It is suspected that eosinophilic dermatosis of hematologic malignancy and EPF may exist on a spectrum, and additional cases may improve categorization of these entities.¹⁹

In conclusion, this report adds to the medical practitioner’s awareness of EPF manifestations in patients with underlying CLL, an infrequently reported subtype of HM-EPF.

To the Editor:

Eosinophilic pustular folliculitis (EPF) is a noninfectious dermatosis that typically manifests as recurrent follicular papulopustules that generally affect the face and occasionally the trunk and arms. There are several subtypes of EPF: classic EPF (Ofuji disease), infancy-associated EPF, and immunosuppression-associated EPF.^1,2 We report a rare case of EPF in the setting of untreated chronic lymphocytic leukemia (CLL), a subtype of immunosuppression­-associated EPF that has been associated with hematologic malignancy EPF (HM-EPF).^3-5

A 69-year-old woman presented with diffusely scattered, pruritic, erythematous, erosive lesions on the back, arms, legs, and forehead (Figure 1) of 4 months’ duration, as well as an ulcerative lesion on the left third toe due to a suspected insect bite. She had a history of untreated CLL that was diagnosed 2 years prior. The patient was empirically started on clindamycin for presumed infection of the toe. A punch biopsy of the left wrist revealed superficial and deep dermal perivascular and interstitial inflammatory infiltrates composed of lymphocytes, histiocytes, and numerous eosinophils in association with edema and necrosis. Histopathology was overall most consistent with an exuberant arthropod reaction; however, at 2-week follow-up, the patient reported that the pustular lesions improved upon starting antibiotics, which raised concerns for a bacterial process. The patient initially was continued on clindamycin given subjective improvement but was later switched to daptomycin, as she developed clindamycin-resistant methicillin-resistant Staphylococcus aureus osteomyelitis from the necrotic toe.

A month later, the patient returned with new papules and pustules on the arms and trunk. A repeat biopsy showed notable dermal collections comprised predominantly of neutrophils and eosinophils as well as involvement of follicular structures by dense inflammation (Figure 2). Immunohistochemistry demonstrated a predominant population of small CD3⁺ T cells, which raised concern for cutaneous T-cell lymphoma. However, retention of CD5 expression made this less likely. Few scattered CD20⁺ B cells with limited CD23 reactivity and without CD5 co-expression were detected, which ruled out cutaneous involvement of the patient’s CLL. Bacterial culture and Grocott methenamine-silver, Gram, acid-fast bacilli, and periodic acid-Schiff stains were negative. Polymerase chain reaction testing for varicella-zoster virus and herpes simplex virus also were negative. Thus, a diagnosis of EPF secondary to CLL was favored, as an infectious process also was unlikely. The patient was started on triamcinolone cream 0.1% with gradual improvement.

Cases of HM-EPF predominantly have been reported in patients who have undergone chemotherapy, bone marrow transplantation, or hematopoietic stem cell transplantation. Furthermore, a vast majority of these cases have been reported in older males.^3-16 In a retrospective study of more than 750 patients with established CLL, Agnew et al⁷ identified 125 different skin complications in 40 patients. Of this subset, only a small number (2/40) were associated with eosinophilic folliculitis, with 1 case noted in a middle-aged woman with a history of CLL treatment.⁷ Moreover, Motaparthi et al⁴ reported 3 additional cases of HM-EPF, with all patients identified as middle-aged men who were treated with chemotherapy for underlying CLL. Our patient represents a case of EPF in the context of untreated CLL in a woman.

Although topical corticosteroids remain the first-line treatment for EPF, a survey study conducted across 67 hospitals in Japan indicated that antibiotics were moderately or highly effective in 79% of EPF patients (n=143).¹⁷ This association may explain the subjective improvement reported by our patient upon starting clindamycin. Furthermore, in HIV-associated EPF, high-dose cetirizine, itraconazole, and metronidazole have been successful when topical therapies have failed.¹⁸ Although the precise pathogenesis of EPF is unknown, histopathologic features, clinical appearance, and identification of the accurate EPF subtype can still prove valuable in informing empiric treatment strategies. Consequently, the initial histopathologic diagnosis of an arthropod bite reaction in our patient highlights the importance of clinical correlation and additional ancillary studies in the determination of EPF vs other inflammatory dermatoses that manifest microscopically with lymphocytic infiltrates, prominent eosinophils, and follicular involvement.⁴ The histopathologic features of EPF demonstrate considerable overlap with eosinophilic dermatosis of hematologic malignancy (also known as eosinophilic dermatosis of myeloproliferative disease). It is suspected that eosinophilic dermatosis of hematologic malignancy and EPF may exist on a spectrum, and additional cases may improve categorization of these entities.¹⁹

In conclusion, this report adds to the medical practitioner’s awareness of EPF manifestations in patients with underlying CLL, an infrequently reported subtype of HM-EPF.

To the Editor:

Eosinophilic pustular folliculitis (EPF) is a noninfectious dermatosis that typically manifests as recurrent follicular papulopustules that generally affect the face and occasionally the trunk and arms. There are several subtypes of EPF: classic EPF (Ofuji disease), infancy-associated EPF, and immunosuppression-associated EPF.^1,2 We report a rare case of EPF in the setting of untreated chronic lymphocytic leukemia (CLL), a subtype of immunosuppression­-associated EPF that has been associated with hematologic malignancy EPF (HM-EPF).^3-5

A 69-year-old woman presented with diffusely scattered, pruritic, erythematous, erosive lesions on the back, arms, legs, and forehead (Figure 1) of 4 months’ duration, as well as an ulcerative lesion on the left third toe due to a suspected insect bite. She had a history of untreated CLL that was diagnosed 2 years prior. The patient was empirically started on clindamycin for presumed infection of the toe. A punch biopsy of the left wrist revealed superficial and deep dermal perivascular and interstitial inflammatory infiltrates composed of lymphocytes, histiocytes, and numerous eosinophils in association with edema and necrosis. Histopathology was overall most consistent with an exuberant arthropod reaction; however, at 2-week follow-up, the patient reported that the pustular lesions improved upon starting antibiotics, which raised concerns for a bacterial process. The patient initially was continued on clindamycin given subjective improvement but was later switched to daptomycin, as she developed clindamycin-resistant methicillin-resistant Staphylococcus aureus osteomyelitis from the necrotic toe.

A month later, the patient returned with new papules and pustules on the arms and trunk. A repeat biopsy showed notable dermal collections comprised predominantly of neutrophils and eosinophils as well as involvement of follicular structures by dense inflammation (Figure 2). Immunohistochemistry demonstrated a predominant population of small CD3⁺ T cells, which raised concern for cutaneous T-cell lymphoma. However, retention of CD5 expression made this less likely. Few scattered CD20⁺ B cells with limited CD23 reactivity and without CD5 co-expression were detected, which ruled out cutaneous involvement of the patient’s CLL. Bacterial culture and Grocott methenamine-silver, Gram, acid-fast bacilli, and periodic acid-Schiff stains were negative. Polymerase chain reaction testing for varicella-zoster virus and herpes simplex virus also were negative. Thus, a diagnosis of EPF secondary to CLL was favored, as an infectious process also was unlikely. The patient was started on triamcinolone cream 0.1% with gradual improvement.

Cases of HM-EPF predominantly have been reported in patients who have undergone chemotherapy, bone marrow transplantation, or hematopoietic stem cell transplantation. Furthermore, a vast majority of these cases have been reported in older males.^3-16 In a retrospective study of more than 750 patients with established CLL, Agnew et al⁷ identified 125 different skin complications in 40 patients. Of this subset, only a small number (2/40) were associated with eosinophilic folliculitis, with 1 case noted in a middle-aged woman with a history of CLL treatment.⁷ Moreover, Motaparthi et al⁴ reported 3 additional cases of HM-EPF, with all patients identified as middle-aged men who were treated with chemotherapy for underlying CLL. Our patient represents a case of EPF in the context of untreated CLL in a woman.

Although topical corticosteroids remain the first-line treatment for EPF, a survey study conducted across 67 hospitals in Japan indicated that antibiotics were moderately or highly effective in 79% of EPF patients (n=143).¹⁷ This association may explain the subjective improvement reported by our patient upon starting clindamycin. Furthermore, in HIV-associated EPF, high-dose cetirizine, itraconazole, and metronidazole have been successful when topical therapies have failed.¹⁸ Although the precise pathogenesis of EPF is unknown, histopathologic features, clinical appearance, and identification of the accurate EPF subtype can still prove valuable in informing empiric treatment strategies. Consequently, the initial histopathologic diagnosis of an arthropod bite reaction in our patient highlights the importance of clinical correlation and additional ancillary studies in the determination of EPF vs other inflammatory dermatoses that manifest microscopically with lymphocytic infiltrates, prominent eosinophils, and follicular involvement.⁴ The histopathologic features of EPF demonstrate considerable overlap with eosinophilic dermatosis of hematologic malignancy (also known as eosinophilic dermatosis of myeloproliferative disease). It is suspected that eosinophilic dermatosis of hematologic malignancy and EPF may exist on a spectrum, and additional cases may improve categorization of these entities.¹⁹

In conclusion, this report adds to the medical practitioner’s awareness of EPF manifestations in patients with underlying CLL, an infrequently reported subtype of HM-EPF.

Lesions of porokeratosis are thought to arise from disordered keratinization, though the exact pathogenesis remains uncertain. At least 5 clinical subtypes of porokeratosis have been identified: porokeratosis of Mibelli, disseminated superficial porokeratosis and disseminated superficial actinic porokeratosis (DSAP), linear porokeratosis, punctuate porokeratosis, and porokeratosis palmaris et plantaris disseminata (PPPD).^1,2 Linear porokeratosis is a rare subtype with a clinical differential diagnosis that includes lichen striatus, linear lichen planus, linear verrucous epidermal nevus, segmental Darier disease, and incontinentia pigmenti.³ Definitive diagnosis of linear porokeratosis is made by histopathologic examination demonstrating a cornoid lamella, defined as a column of parakeratotic cells that lies at 45°to the surface of the epidermis and contains pyknotic basophilic nuclei.⁴ Patients with linear porokeratosis typically develop lesions along the lines of Blaschko in infancy or childhood.^5,6 Among the different subtypes of porokeratosis, linear porokeratosis demonstrates the highest rate of malignant transformation, therefore requiring close clinical observation.⁷

Case Report

An 83-year-old woman presented to the outpatient clinic with a large linear plaque on the right leg that had been present since birth. Ten years prior to presentation, a portion of the lesion started to bleed; biopsy of the area was performed by an outside provider demonstrating squamous cell carcinoma (SCC), which was treated with wide local excision. One year prior to presentation, a separate portion of the plaque was biopsied by an outside provider and another diagnosis of SCC was made.

On examination performed during the initial presentation to our clinic, there was a well-demarcated tan to violaceous linear plaque present at the lower buttock and extending along the posterior leg to the skin overlying the Achilles tendon and dorsal aspect of the right foot. Within the plaque, there were areas of atrophy and areas of inflammation, induration, and hyperkeratosis (Figures 1 and 2). Two punch biopsies were performed: one from the edge of the plaque and one from a hyperkeratotic region within the plaque. Histology from the edge of the plaque demonstrated a cornoid lamella, consistent with a porokeratosis (Figure 3), whereas the histology from the hyperkeratotic region demonstrated a lichenoid infiltrate (Figure 4).

Several treatment options directed at the entire lesion were offered to the patient, but she declined these therapies and opted to address only those areas with clinical features of SCC, such as hyperkeratosis, bleeding, and rapid growth. Although biopsies performed by an outside provider were consistent with SCC, it had not been detected on biopsy performed during her initial visit to our clinic.

The patient was educated on the risk associated with her condition and instructed to follow up every 6 months to monitor for the development of SCC.

Comment

Porokeratosis is a disorder of keratinization with at least 5 clinical subtypes that share histologic similarities: porokeratosis of Mibelli, disseminated superficial porokeratosis and DSAP, linear porokeratosis, punctate porokeratosis, and PPPD.^1,2 Other less common variants of porokeratosis include porokeratosis ptychotropica (a verrucous variant confined to the perianal area) and congenital unilateral linear porokeratosis.^8,9

Linear porokeratosis appears in infancy or childhood with plaques that follow the lines of Blaschko.^5,6 Most commonly, it presents unilaterally with annular plaques and linear hyperkeratotic papules that preferentially affect the extremities, though it also may present in a more generalized form or appear in a zosteriform pattern.^10,11 Linear porokeratosis affects fewer than 20,000 individuals in the United States and accounts for fewer than 13% of all porokeratosis cases.^12,13

Despite its relatively low prevalence, early identification of linear porokeratosis is important due to its high oncogenic potential, with malignant transformation to basal cell carcinoma or, more commonly, SCC reported in 19% of reported cases.^1,5,7,14 The malignant transformation rate of linear porokeratosis is reported to be higher than rates seen in other porokeratosis subtypes (9.5%, 7.6%, and 3.4% for PPPD, porokeratosis of Mibelli, and DSAP, respectively).⁷ The risk of malignant transformation from porokeratosis increases with exposure to ionizing radiation, duration of the lesion, larger or coalescing lesions, and advanced age.^7,15,16 Histologic studies have provided support for correlation between lesion size and oncogenic potential, with greater numbers of mitotic cells and more abnormal DNA ploidy seen in larger lesions.¹⁷

Histopathology
All subtypes of porokeratosis share certain histopathologic features that aid in the diagnosis of the disorder.¹⁸ Identification of the clinically observed hyperkeratotic ridged border or cornoid lamella is the primary means of definitively diagnosing porokeratosis; however, cornoid lamellae may be observed in other conditions, including verruca vulgaris and actinic keratosis.^4,14

The cornoid lamella appears as a skewed column of densely packed parakeratotic cells with pyknotic basophilic nuclei extending through the stratum corneum from an epidermal invagination.⁴ Directly beneath the cornoid lamella, the granular layer is markedly diminished or absent, and cells of the stratum spinosum may demonstrate vacuolar changes or dyskeratosis.^4,19 The superficial layer of the cornoid lamella may appear to be more centrifugally located and the cornoid lamella may be seen in several locations throughout the lesion.^2,20 The degree of epidermal invagination, which is present under the cornoid lamella, varies by porokeratosis subtype; the central portion of the lesion may contain epidermis that ranges from hyperplastic to atrophic.² Shumack et al²¹ noted that histologic changes under the cornoid lamella may include a lichenoid tissue reaction, papillary dermal lymphocytic infiltrate, vacuolar changes, dyskeratosis, and liquefaction degeneration of the basal layer. Because many of these histologic features also can be identified in lichen planus, a biopsy of the edge of lesions of porokeratosis is essential for making the correct diagnosis.

Heritability
Although linear porokeratosis has no identified pattern of inheritance and appears sporadic in onset, reports have described concomitant occurrence of linear porokeratosis and DSAP as well as linear porokeratosis arising in children of parents who have a diagnosis of DSAP.^5,18,22,23 Based on these findings, it has been hypothesized that linear porokeratosis may represent a mosaic or segmental form of autosomal-dominant inherited subtypes of porokeratosis, such as DSAP.⁵ According to this hypothesis, loss of heterozygosity in patients with a DSAP mutation during early embryogenesis leads to proliferation of cells that are homozygous or hemizygous for the underlying mutation along lines of Blaschko.²⁴ It has been suggested that the allelic loss implicated in the development of linear porokeratosis is the first step in a multistage process of carcinogenesis, which may help to explain the higher rates of malignant transformation that can be seen in linear porokeratosis.²⁴

Management
Several treatment options exist for porokeratosis, including cryotherapy, topical 5-fluorouracil with or without adjunctive retinoid treatment, topical imiquimod, CO₂ laser, shave and linear excision, curettage, dermabrasion, and oral acitretin for widespread lesions.^1,25-29 One case report detailed successful treatment of adult-onset linear porokeratosis with tacrolimus ointment 0.1%.³⁰ Treatments for porokeratosis demonstrate variable degrees of success, with the aim of eradicating the clonal population of mutant keratinocytes.² Additionally, protection from UV radiation should be encouraged, especially in patients who have lesions that occur in areas of high actinic damage.¹

Conclusion

We report of a case of linear porokeratosis with associated multiple SCCs that developed within the lesion. Definitive diagnosis of linear porokeratosis is important due to the higher rate of malignant transformation than the rate seen in other porokeratoses. In larger lesions, appropriate sampling and orientation of the pathology specimen is essential for identifying cornoid lamellae, thus allowing for appropriate follow-up and management. Several treatment options are available, though evidence for the effectiveness of any particular therapy is lacking. Research has shed light on possible genetic and molecular abnormalities in linear porokeratosis, but the exact pathogenesis of the disorder remains unclear.

Lesions of porokeratosis are thought to arise from disordered keratinization, though the exact pathogenesis remains uncertain. At least 5 clinical subtypes of porokeratosis have been identified: porokeratosis of Mibelli, disseminated superficial porokeratosis and disseminated superficial actinic porokeratosis (DSAP), linear porokeratosis, punctuate porokeratosis, and porokeratosis palmaris et plantaris disseminata (PPPD).^1,2 Linear porokeratosis is a rare subtype with a clinical differential diagnosis that includes lichen striatus, linear lichen planus, linear verrucous epidermal nevus, segmental Darier disease, and incontinentia pigmenti.³ Definitive diagnosis of linear porokeratosis is made by histopathologic examination demonstrating a cornoid lamella, defined as a column of parakeratotic cells that lies at 45°to the surface of the epidermis and contains pyknotic basophilic nuclei.⁴ Patients with linear porokeratosis typically develop lesions along the lines of Blaschko in infancy or childhood.^5,6 Among the different subtypes of porokeratosis, linear porokeratosis demonstrates the highest rate of malignant transformation, therefore requiring close clinical observation.⁷

Case Report

An 83-year-old woman presented to the outpatient clinic with a large linear plaque on the right leg that had been present since birth. Ten years prior to presentation, a portion of the lesion started to bleed; biopsy of the area was performed by an outside provider demonstrating squamous cell carcinoma (SCC), which was treated with wide local excision. One year prior to presentation, a separate portion of the plaque was biopsied by an outside provider and another diagnosis of SCC was made.

On examination performed during the initial presentation to our clinic, there was a well-demarcated tan to violaceous linear plaque present at the lower buttock and extending along the posterior leg to the skin overlying the Achilles tendon and dorsal aspect of the right foot. Within the plaque, there were areas of atrophy and areas of inflammation, induration, and hyperkeratosis (Figures 1 and 2). Two punch biopsies were performed: one from the edge of the plaque and one from a hyperkeratotic region within the plaque. Histology from the edge of the plaque demonstrated a cornoid lamella, consistent with a porokeratosis (Figure 3), whereas the histology from the hyperkeratotic region demonstrated a lichenoid infiltrate (Figure 4).

Several treatment options directed at the entire lesion were offered to the patient, but she declined these therapies and opted to address only those areas with clinical features of SCC, such as hyperkeratosis, bleeding, and rapid growth. Although biopsies performed by an outside provider were consistent with SCC, it had not been detected on biopsy performed during her initial visit to our clinic.

The patient was educated on the risk associated with her condition and instructed to follow up every 6 months to monitor for the development of SCC.

Comment

Porokeratosis is a disorder of keratinization with at least 5 clinical subtypes that share histologic similarities: porokeratosis of Mibelli, disseminated superficial porokeratosis and DSAP, linear porokeratosis, punctate porokeratosis, and PPPD.^1,2 Other less common variants of porokeratosis include porokeratosis ptychotropica (a verrucous variant confined to the perianal area) and congenital unilateral linear porokeratosis.^8,9

Linear porokeratosis appears in infancy or childhood with plaques that follow the lines of Blaschko.^5,6 Most commonly, it presents unilaterally with annular plaques and linear hyperkeratotic papules that preferentially affect the extremities, though it also may present in a more generalized form or appear in a zosteriform pattern.^10,11 Linear porokeratosis affects fewer than 20,000 individuals in the United States and accounts for fewer than 13% of all porokeratosis cases.^12,13

Despite its relatively low prevalence, early identification of linear porokeratosis is important due to its high oncogenic potential, with malignant transformation to basal cell carcinoma or, more commonly, SCC reported in 19% of reported cases.^1,5,7,14 The malignant transformation rate of linear porokeratosis is reported to be higher than rates seen in other porokeratosis subtypes (9.5%, 7.6%, and 3.4% for PPPD, porokeratosis of Mibelli, and DSAP, respectively).⁷ The risk of malignant transformation from porokeratosis increases with exposure to ionizing radiation, duration of the lesion, larger or coalescing lesions, and advanced age.^7,15,16 Histologic studies have provided support for correlation between lesion size and oncogenic potential, with greater numbers of mitotic cells and more abnormal DNA ploidy seen in larger lesions.¹⁷

Histopathology
All subtypes of porokeratosis share certain histopathologic features that aid in the diagnosis of the disorder.¹⁸ Identification of the clinically observed hyperkeratotic ridged border or cornoid lamella is the primary means of definitively diagnosing porokeratosis; however, cornoid lamellae may be observed in other conditions, including verruca vulgaris and actinic keratosis.^4,14

The cornoid lamella appears as a skewed column of densely packed parakeratotic cells with pyknotic basophilic nuclei extending through the stratum corneum from an epidermal invagination.⁴ Directly beneath the cornoid lamella, the granular layer is markedly diminished or absent, and cells of the stratum spinosum may demonstrate vacuolar changes or dyskeratosis.^4,19 The superficial layer of the cornoid lamella may appear to be more centrifugally located and the cornoid lamella may be seen in several locations throughout the lesion.^2,20 The degree of epidermal invagination, which is present under the cornoid lamella, varies by porokeratosis subtype; the central portion of the lesion may contain epidermis that ranges from hyperplastic to atrophic.² Shumack et al²¹ noted that histologic changes under the cornoid lamella may include a lichenoid tissue reaction, papillary dermal lymphocytic infiltrate, vacuolar changes, dyskeratosis, and liquefaction degeneration of the basal layer. Because many of these histologic features also can be identified in lichen planus, a biopsy of the edge of lesions of porokeratosis is essential for making the correct diagnosis.

Heritability
Although linear porokeratosis has no identified pattern of inheritance and appears sporadic in onset, reports have described concomitant occurrence of linear porokeratosis and DSAP as well as linear porokeratosis arising in children of parents who have a diagnosis of DSAP.^5,18,22,23 Based on these findings, it has been hypothesized that linear porokeratosis may represent a mosaic or segmental form of autosomal-dominant inherited subtypes of porokeratosis, such as DSAP.⁵ According to this hypothesis, loss of heterozygosity in patients with a DSAP mutation during early embryogenesis leads to proliferation of cells that are homozygous or hemizygous for the underlying mutation along lines of Blaschko.²⁴ It has been suggested that the allelic loss implicated in the development of linear porokeratosis is the first step in a multistage process of carcinogenesis, which may help to explain the higher rates of malignant transformation that can be seen in linear porokeratosis.²⁴

Management
Several treatment options exist for porokeratosis, including cryotherapy, topical 5-fluorouracil with or without adjunctive retinoid treatment, topical imiquimod, CO₂ laser, shave and linear excision, curettage, dermabrasion, and oral acitretin for widespread lesions.^1,25-29 One case report detailed successful treatment of adult-onset linear porokeratosis with tacrolimus ointment 0.1%.³⁰ Treatments for porokeratosis demonstrate variable degrees of success, with the aim of eradicating the clonal population of mutant keratinocytes.² Additionally, protection from UV radiation should be encouraged, especially in patients who have lesions that occur in areas of high actinic damage.¹

Conclusion

We report of a case of linear porokeratosis with associated multiple SCCs that developed within the lesion. Definitive diagnosis of linear porokeratosis is important due to the higher rate of malignant transformation than the rate seen in other porokeratoses. In larger lesions, appropriate sampling and orientation of the pathology specimen is essential for identifying cornoid lamellae, thus allowing for appropriate follow-up and management. Several treatment options are available, though evidence for the effectiveness of any particular therapy is lacking. Research has shed light on possible genetic and molecular abnormalities in linear porokeratosis, but the exact pathogenesis of the disorder remains unclear.

Lesions of porokeratosis are thought to arise from disordered keratinization, though the exact pathogenesis remains uncertain. At least 5 clinical subtypes of porokeratosis have been identified: porokeratosis of Mibelli, disseminated superficial porokeratosis and disseminated superficial actinic porokeratosis (DSAP), linear porokeratosis, punctuate porokeratosis, and porokeratosis palmaris et plantaris disseminata (PPPD).^1,2 Linear porokeratosis is a rare subtype with a clinical differential diagnosis that includes lichen striatus, linear lichen planus, linear verrucous epidermal nevus, segmental Darier disease, and incontinentia pigmenti.³ Definitive diagnosis of linear porokeratosis is made by histopathologic examination demonstrating a cornoid lamella, defined as a column of parakeratotic cells that lies at 45°to the surface of the epidermis and contains pyknotic basophilic nuclei.⁴ Patients with linear porokeratosis typically develop lesions along the lines of Blaschko in infancy or childhood.^5,6 Among the different subtypes of porokeratosis, linear porokeratosis demonstrates the highest rate of malignant transformation, therefore requiring close clinical observation.⁷

Case Report

An 83-year-old woman presented to the outpatient clinic with a large linear plaque on the right leg that had been present since birth. Ten years prior to presentation, a portion of the lesion started to bleed; biopsy of the area was performed by an outside provider demonstrating squamous cell carcinoma (SCC), which was treated with wide local excision. One year prior to presentation, a separate portion of the plaque was biopsied by an outside provider and another diagnosis of SCC was made.

On examination performed during the initial presentation to our clinic, there was a well-demarcated tan to violaceous linear plaque present at the lower buttock and extending along the posterior leg to the skin overlying the Achilles tendon and dorsal aspect of the right foot. Within the plaque, there were areas of atrophy and areas of inflammation, induration, and hyperkeratosis (Figures 1 and 2). Two punch biopsies were performed: one from the edge of the plaque and one from a hyperkeratotic region within the plaque. Histology from the edge of the plaque demonstrated a cornoid lamella, consistent with a porokeratosis (Figure 3), whereas the histology from the hyperkeratotic region demonstrated a lichenoid infiltrate (Figure 4).

Several treatment options directed at the entire lesion were offered to the patient, but she declined these therapies and opted to address only those areas with clinical features of SCC, such as hyperkeratosis, bleeding, and rapid growth. Although biopsies performed by an outside provider were consistent with SCC, it had not been detected on biopsy performed during her initial visit to our clinic.

The patient was educated on the risk associated with her condition and instructed to follow up every 6 months to monitor for the development of SCC.

Comment

Porokeratosis is a disorder of keratinization with at least 5 clinical subtypes that share histologic similarities: porokeratosis of Mibelli, disseminated superficial porokeratosis and DSAP, linear porokeratosis, punctate porokeratosis, and PPPD.^1,2 Other less common variants of porokeratosis include porokeratosis ptychotropica (a verrucous variant confined to the perianal area) and congenital unilateral linear porokeratosis.^8,9

Linear porokeratosis appears in infancy or childhood with plaques that follow the lines of Blaschko.^5,6 Most commonly, it presents unilaterally with annular plaques and linear hyperkeratotic papules that preferentially affect the extremities, though it also may present in a more generalized form or appear in a zosteriform pattern.^10,11 Linear porokeratosis affects fewer than 20,000 individuals in the United States and accounts for fewer than 13% of all porokeratosis cases.^12,13

Despite its relatively low prevalence, early identification of linear porokeratosis is important due to its high oncogenic potential, with malignant transformation to basal cell carcinoma or, more commonly, SCC reported in 19% of reported cases.^1,5,7,14 The malignant transformation rate of linear porokeratosis is reported to be higher than rates seen in other porokeratosis subtypes (9.5%, 7.6%, and 3.4% for PPPD, porokeratosis of Mibelli, and DSAP, respectively).⁷ The risk of malignant transformation from porokeratosis increases with exposure to ionizing radiation, duration of the lesion, larger or coalescing lesions, and advanced age.^7,15,16 Histologic studies have provided support for correlation between lesion size and oncogenic potential, with greater numbers of mitotic cells and more abnormal DNA ploidy seen in larger lesions.¹⁷

Histopathology
All subtypes of porokeratosis share certain histopathologic features that aid in the diagnosis of the disorder.¹⁸ Identification of the clinically observed hyperkeratotic ridged border or cornoid lamella is the primary means of definitively diagnosing porokeratosis; however, cornoid lamellae may be observed in other conditions, including verruca vulgaris and actinic keratosis.^4,14

The cornoid lamella appears as a skewed column of densely packed parakeratotic cells with pyknotic basophilic nuclei extending through the stratum corneum from an epidermal invagination.⁴ Directly beneath the cornoid lamella, the granular layer is markedly diminished or absent, and cells of the stratum spinosum may demonstrate vacuolar changes or dyskeratosis.^4,19 The superficial layer of the cornoid lamella may appear to be more centrifugally located and the cornoid lamella may be seen in several locations throughout the lesion.^2,20 The degree of epidermal invagination, which is present under the cornoid lamella, varies by porokeratosis subtype; the central portion of the lesion may contain epidermis that ranges from hyperplastic to atrophic.² Shumack et al²¹ noted that histologic changes under the cornoid lamella may include a lichenoid tissue reaction, papillary dermal lymphocytic infiltrate, vacuolar changes, dyskeratosis, and liquefaction degeneration of the basal layer. Because many of these histologic features also can be identified in lichen planus, a biopsy of the edge of lesions of porokeratosis is essential for making the correct diagnosis.

Heritability
Although linear porokeratosis has no identified pattern of inheritance and appears sporadic in onset, reports have described concomitant occurrence of linear porokeratosis and DSAP as well as linear porokeratosis arising in children of parents who have a diagnosis of DSAP.^5,18,22,23 Based on these findings, it has been hypothesized that linear porokeratosis may represent a mosaic or segmental form of autosomal-dominant inherited subtypes of porokeratosis, such as DSAP.⁵ According to this hypothesis, loss of heterozygosity in patients with a DSAP mutation during early embryogenesis leads to proliferation of cells that are homozygous or hemizygous for the underlying mutation along lines of Blaschko.²⁴ It has been suggested that the allelic loss implicated in the development of linear porokeratosis is the first step in a multistage process of carcinogenesis, which may help to explain the higher rates of malignant transformation that can be seen in linear porokeratosis.²⁴

Management
Several treatment options exist for porokeratosis, including cryotherapy, topical 5-fluorouracil with or without adjunctive retinoid treatment, topical imiquimod, CO₂ laser, shave and linear excision, curettage, dermabrasion, and oral acitretin for widespread lesions.^1,25-29 One case report detailed successful treatment of adult-onset linear porokeratosis with tacrolimus ointment 0.1%.³⁰ Treatments for porokeratosis demonstrate variable degrees of success, with the aim of eradicating the clonal population of mutant keratinocytes.² Additionally, protection from UV radiation should be encouraged, especially in patients who have lesions that occur in areas of high actinic damage.¹

Conclusion

We report of a case of linear porokeratosis with associated multiple SCCs that developed within the lesion. Definitive diagnosis of linear porokeratosis is important due to the higher rate of malignant transformation than the rate seen in other porokeratoses. In larger lesions, appropriate sampling and orientation of the pathology specimen is essential for identifying cornoid lamellae, thus allowing for appropriate follow-up and management. Several treatment options are available, though evidence for the effectiveness of any particular therapy is lacking. Research has shed light on possible genetic and molecular abnormalities in linear porokeratosis, but the exact pathogenesis of the disorder remains unclear.