PAGET'S DISEASE
Diagnosis
Perianal Paget's is quite uncommon, with only 195 cases reported in the literature from 1963 to 1995.13 It is an intraepithelial adenocarcinoma arising from the dermal apocrine sweat glands. It is most commonly found in older patients (average age 66 years), shows a preponderance for women, and is often initially confused with benign conditions, which can lead to a delay in diagnosis. Perianal Paget's should be considered in patients who present with perianal itching or rash refractory to local therapy. There may also be drainage, bleeding, or pain. Lesions are usually erythematous and crusty, eczematoid, or scaly-appearing. Differential diagnosis includes leukoplakia, Bowen's disease, melanoma, basal and squamous cell carcinoma, condylomata acuminata, dermatitis, eczema, and psoriasis.14,15
Full-thickness biopsies of the affected anal margin skin must be obtained. Perianal mapping biopsies should be obtained; the accepted method is described in the section on Bowen's disease. Microscopic examination of perianal skin affected by Paget's disease will show classic Paget cells, which appear as large rounded cells with pale vacuolated cytoplasm and hyperchromatic eccentric nuclei.16 There may be hyperkeratosis, parakeratosis, and acanthosis of the epidermal cells. Periodic acid-Schiff stain (PAS) may identify sialomucin, whereas Bowen's disease does not display positive PAS staining. A correct diagnosis is important for treatment and prognosis; though progression to invasive cancer occurs in ~5% of Bowen's cases, invasive cancer has been reported in up to 40% of patients with untreated Paget's disease.
Management
After exclusion of other potential perianal diseases and proper diagnosis of perianal Paget's disease on a histologic basis, treatment is essentially surgical in nature. However, prior to proceeding with local treatment exclusion of an associated underlying malignancy is obligatory. Mammary Paget's is generally associated with underlying ductal carcinoma. In contrast, extramammary disease is associated with an underlying neoplasm in a significant percentage of cases.17 Association with tuboovarian adenocarcinoma is seen in 7 to 24% of cases and gastrointestinal carcinoma in 12 to 14% of cases.18,19 Appropriate imaging studies and fiberoptic endoscopy are recommended preoperatively to rule out other associated malignancies, the presence of which may alter treatment recommendations.20
If the disease appears to be locally confined on preoperative workup and is noninvasive on biopsy, wide local excision is the treatment of choice.15,18,20,21 Because Paget's disease can extend horizontally in the dermis well beyond the boundary of clinically evident disease, it is imperative to perform perianal mapping biopsies prior to formal wide excision. As traditional frozen section without histochemical staining may show falsely negative results, perianal mapping biopsies should be done several days before definitive treatment.15 Groin lymph node dissection should be performed if the patient presents with clinically positive nodes and should be considered if Paget's cells are seen throughout the dermis on histologic inspection of the resected specimen. If an associated malignancy of the anorectum is detected on preoperative workup, an APR is the procedure of choice to treat the anorectal cancer with the addition of wide local excision to treat the cutaneous Paget's disease20 (Table 2). More advanced tumors may benefit from preoperative radiation or chemoradiation therapy; however the use of these modalities in the treatment of perianal Paget's remains controversial.
Table 2
Table 2
Staging and Treatment for Perianal Paget's Disease
Although primary closure of the resulting defect after wide local excision is often possible, several methods have been described to provide coverage for defects too large for primary closure including myocutaneous flaps, rotational or advancement skin flaps, as well as skin grafting.15,22 Although fecal diversion is not mandatory for all flap closures, larger defects requiring flap or graft closure may benefit from proximal fecal diversion to prevent wound infection and subsequent flap failure. In general, defects involving more than half the circumference of the anus or those with a radius of more than 3 cm should be considered for diversion.23 We feel that absolute size of the defect is less important than the amount of the circumference of anal margin skin that is involved. Proximal diversion can lower rates of wound infection, which may result in higher incidences of dehiscence, prolonged recovery, and ultimately poor functional outcome, especially for larger flaps.20
Several noninvasive modalities have been proposed as well for the treatment of perianal Paget's disease including radiation therapy, chemotherapy, photodynamic therapy, and topical imiquimod.24,25,26 Patients who have multifocal widespread cutaneous disease may benefit most from these therapies, either alone or in conjunction with wide local excision of disease that is clinically evident on physical examination. Unfortunately, because the number of patients in these reports is quite small, it is difficult to objectively compare these modalities, and they are often reserved for medically high-risk patients or those who refuse to undergo more radical therapy.
Patients who present with a more advanced stage of perianal Paget's disease tend to have a worse prognosis than patients in whom disease is confined to the epidermis.15,20,21 The largest series of patients in the literature is from McCarter et al consisting of 27 patients treated at Memorial Sloan-Kettering Cancer Center between 1950 and 2000. The overall disease-free 5-year survival rate of patients without an invasive component was 64% compared with 59% in those with an invasive component.21
Local recurrence has been reported to be as high as 60% in some series, and may be higher in patients with more advanced or multifocal disease.15,27 Although there is some variation with regard to recommendations for follow-up of these patients, most authors agree that annual physical examination and random perianal skin biopsies is appropriate.20 Fiberoptic endoscopy is recommended every 2 to 3 years as well because of the association with underlying gastrointestinal malignancy. Wolfgang et al also recommend a CT scan every 1 to 2 years.20 Obviously, any of these tests may be performed earlier if warranted clinically.
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Diagnosis
Perianal Paget's is quite uncommon, with only 195 cases reported in the literature from 1963 to 1995.13 It is an intraepithelial adenocarcinoma arising from the dermal apocrine sweat glands. It is most commonly found in older patients (average age 66 years), shows a preponderance for women, and is often initially confused with benign conditions, which can lead to a delay in diagnosis. Perianal Paget's should be considered in patients who present with perianal itching or rash refractory to local therapy. There may also be drainage, bleeding, or pain. Lesions are usually erythematous and crusty, eczematoid, or scaly-appearing. Differential diagnosis includes leukoplakia, Bowen's disease, melanoma, basal and squamous cell carcinoma, condylomata acuminata, dermatitis, eczema, and psoriasis.14,15
Full-thickness biopsies of the affected anal margin skin must be obtained. Perianal mapping biopsies should be obtained; the accepted method is described in the section on Bowen's disease. Microscopic examination of perianal skin affected by Paget's disease will show classic Paget cells, which appear as large rounded cells with pale vacuolated cytoplasm and hyperchromatic eccentric nuclei.16 There may be hyperkeratosis, parakeratosis, and acanthosis of the epidermal cells. Periodic acid-Schiff stain (PAS) may identify sialomucin, whereas Bowen's disease does not display positive PAS staining. A correct diagnosis is important for treatment and prognosis; though progression to invasive cancer occurs in ~5% of Bowen's cases, invasive cancer has been reported in up to 40% of patients with untreated Paget's disease.
Management
After exclusion of other potential perianal diseases and proper diagnosis of perianal Paget's disease on a histologic basis, treatment is essentially surgical in nature. However, prior to proceeding with local treatment exclusion of an associated underlying malignancy is obligatory. Mammary Paget's is generally associated with underlying ductal carcinoma. In contrast, extramammary disease is associated with an underlying neoplasm in a significant percentage of cases.17 Association with tuboovarian adenocarcinoma is seen in 7 to 24% of cases and gastrointestinal carcinoma in 12 to 14% of cases.18,19 Appropriate imaging studies and fiberoptic endoscopy are recommended preoperatively to rule out other associated malignancies, the presence of which may alter treatment recommendations.20
If the disease appears to be locally confined on preoperative workup and is noninvasive on biopsy, wide local excision is the treatment of choice.15,18,20,21 Because Paget's disease can extend horizontally in the dermis well beyond the boundary of clinically evident disease, it is imperative to perform perianal mapping biopsies prior to formal wide excision. As traditional frozen section without histochemical staining may show falsely negative results, perianal mapping biopsies should be done several days before definitive treatment.15 Groin lymph node dissection should be performed if the patient presents with clinically positive nodes and should be considered if Paget's cells are seen throughout the dermis on histologic inspection of the resected specimen. If an associated malignancy of the anorectum is detected on preoperative workup, an APR is the procedure of choice to treat the anorectal cancer with the addition of wide local excision to treat the cutaneous Paget's disease20 (Table 2). More advanced tumors may benefit from preoperative radiation or chemoradiation therapy; however the use of these modalities in the treatment of perianal Paget's remains controversial.
Table 2
Table 2
Staging and Treatment for Perianal Paget's Disease
Although primary closure of the resulting defect after wide local excision is often possible, several methods have been described to provide coverage for defects too large for primary closure including myocutaneous flaps, rotational or advancement skin flaps, as well as skin grafting.15,22 Although fecal diversion is not mandatory for all flap closures, larger defects requiring flap or graft closure may benefit from proximal fecal diversion to prevent wound infection and subsequent flap failure. In general, defects involving more than half the circumference of the anus or those with a radius of more than 3 cm should be considered for diversion.23 We feel that absolute size of the defect is less important than the amount of the circumference of anal margin skin that is involved. Proximal diversion can lower rates of wound infection, which may result in higher incidences of dehiscence, prolonged recovery, and ultimately poor functional outcome, especially for larger flaps.20
Several noninvasive modalities have been proposed as well for the treatment of perianal Paget's disease including radiation therapy, chemotherapy, photodynamic therapy, and topical imiquimod.24,25,26 Patients who have multifocal widespread cutaneous disease may benefit most from these therapies, either alone or in conjunction with wide local excision of disease that is clinically evident on physical examination. Unfortunately, because the number of patients in these reports is quite small, it is difficult to objectively compare these modalities, and they are often reserved for medically high-risk patients or those who refuse to undergo more radical therapy.
Patients who present with a more advanced stage of perianal Paget's disease tend to have a worse prognosis than patients in whom disease is confined to the epidermis.15,20,21 The largest series of patients in the literature is from McCarter et al consisting of 27 patients treated at Memorial Sloan-Kettering Cancer Center between 1950 and 2000. The overall disease-free 5-year survival rate of patients without an invasive component was 64% compared with 59% in those with an invasive component.21
Local recurrence has been reported to be as high as 60% in some series, and may be higher in patients with more advanced or multifocal disease.15,27 Although there is some variation with regard to recommendations for follow-up of these patients, most authors agree that annual physical examination and random perianal skin biopsies is appropriate.20 Fiberoptic endoscopy is recommended every 2 to 3 years as well because of the association with underlying gastrointestinal malignancy. Wolfgang et al also recommend a CT scan every 1 to 2 years.20 Obviously, any of these tests may be performed earlier if warranted clinically.
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