Brain metastasis from extramammary Paget's disease.

Herein, we present a case of extramammary Paget's disease with brain metastasis that was diagnosed pathologically for the first time in Japan. Moreover, invasive extramammary Paget's disease (with distant metastasis) highly resistant to treatment. Only for brain metastasis, we may control the tumor by surgical resection and stereotactic radiosurgery (SRT) for the treatment of intracranial metastases was assessed. An 76-year-old man was diagnosed with extramammary Paget's disease of the vulva at nearby hospital. Surgical resection and sentinel lymph node dissection were then performed, and the patient received chemotherapy because multiple lymph node metastases were suspected. The patient's response to chemotherapy was poor, and he was in the state of Progressive Disease. He complained of dyslexia and was referred to another hospital when he was 81 years old. Plain magnetic resonance imaging (MRI) was conducted, and two brain tumors in the vicinity of the left cerebellar tent were suspected. In our hospital, gadolinium contrast-enhanced MRI was performed and showed a tumor in the cerebellum (left posterior temporal lobe) and another tumor under the tent (left cerebellar hemisphere). Significant edema was also noted. Based on these findings, the intracranial lesion was diagnosed as metastatic brain tumor. The pathological diagnosis was brain metastasis from extramammary Paget's disease. Postoperative intracranial residual disease was treated with stereotactic radiosurgery. MRI showed that the size of the cerebellar lesions decreased, and no recurrence of cerebral lesions was observed. SRT for extracranial lymph node metastases was performed. Mass reduction and SRT may be the best way to treat brain metastasis from extramammary Paget's disease.

Extramammary Paget Disease of the Scrotum: A Contemporary Clinicopathologic Analysis of 20 Cases in the United States.

Extramammary Paget disease (EMPD) often involves apocrine gland-bearing locations including vulva and perianal area. EMPD of the scrotum is rare. Twenty patients were identified from the pathology files of 4 institutions between 2000 and 2018. Patients were 63- to 87-year-old (mean: 73 y) with a history of symptoms of between 4 months and 10 years. Two patients had a history of prostate cancer. Follow-up was available in 11 patients for a median of 71 months (range: 8 to 126 mo). Nine of 11 patients (82%) had positive margins, and 73% required reexcisions. Three patients had a focal dermal invasion, 1 of whom reportedly died of another etiology 25 months post diagnosis and 2 were disease-free at 24 and 68 months. No patient had inguinal lymphadenopathy. Two patients were alive with disease. Immunohistochemically, GATA3 and GCDFP15 were expressed in 6/6 cases, CK7 in 8/8 cases, and androgen receptor in 13/13 cases. HER2 was positive in 5/12 cases. PSA was positive in 1 patient who had a history of prostate cancer, whereas other prostate markers (NKX3.1 and prostein) were negative, and CK7 and GCDFP15 were positive, rendering primary EMPD diagnosis. Twelve other cases were negative for PSA and NKX3.1. In conclusion, EMPD of the scrotum has an insidious onset and its nonspecific symptoms can be misdiagnosed as dermatitis or fungal infection. Although localized EMPD has a favorable prognosis, the invasive disease is rare and did not predict metastasis or progression. Margins are frequently positive requiring reexcision. Occasionally, cases can be positive for PSA leading to diagnostic pitfalls.

Extramammary Paget's disease: what do we know and how do we treat?

INTRODUCTION: Extramammary Paget's disease (EMPD) is a rare and complex condition, for which no established guidelines exist regarding diagnosis and management. There have been recent improvements in the diagnosis and management in EMPD, largely due to an enhanced understanding of its underlying pathogenesis. MATERIALS AND METHODS: A literature search on PubMed including articles that describe pathogenesis, clinical diagnosis, treatment modalities, and future treatment were selected and included to build this review. RESULTS: Recent studies would suggest the expression of HER2 and androgen receptors which could be useful targets for future treatment strategies. Carcinoembryonic antigen as a biomarker for EMPD has shown the potential to aid in the detection of metastatic EMPD and assessment of treatment response. Studies have also demonstrated the initial site of EMPD can be predictive of secondary malignancies, which helps guide initial work up and evaluation. CONCLUSIONS: Significant developments in understanding the pathogenesis of EMPD have been made, especially of the genomic aberrations associated with EMPD. This has allowed for the development and use of therapeutic options which may improve outcomes for patients with EMPD.

A novel technique to diagnose non-melanoma skin cancer by thermal conductivity measurements: Correlations with cancer stromal factors.

The skin surface temperature reflects the physiological state of the human body. Quantitative methods of identification of skin cancers based on accurate measurement of effective thermal conductivity (ETC) are among the promising diagnostic tools for differentiating non-invasive and invasive melanomas before surgical treatment. To validate these findings, in this report, the diagnostic methods for invasive and non-invasive extramammary Paget's disease (EMPD) and squamous cell carcinoma (SCC) were further tested by measuring the absolute value of skin surface temperature and the ETC of the skin. In addition, to investigate the stromal factors that might affect ETC, immunohistochemical staining for LL37, periostin (POSTN), MMP12, and MMP28 was performed. The invasive SCC and EMPD group showed a relatively higher skin surface temperature compared to the in situ SCC group. The non-invasive EMPD and SCC group showed significantly lower values of ETC at lesions, whereas the invasive EMPD group showed significantly higher ETC values at lesions compared to healthy skin. Immunohistochemical staining showed that the percentage of LL37-producing cells was significantly increased in invasive EMPD and SCC compared to that in non-invasive EMPD and SCC. Moreover, Spearman's rank correlation test showed a significant inverse correlation between the percentage of MMP12-positive cells and increased levels of ETC-expressing areas in EMPD and SCC (r = -.5997). The present study suggested that differences in ETC could be a novel high-accuracy diagnostic technique for non-melanoma skin cancer, especially for detecting dermal invasion of SCC and EMPD.

Management of extramammary Paget's disease with a staged, modified Mohs technique.

Extramammary Paget's disease (EMPD) is a rare intraepithelial adenocarcinoma arising from apocrine glands. We describe an innovative surgical technique to manage extensive cutaneous malignancies in a notoriously challenging location. The patient is a 78-year-old male who presented with 'jock itch' on his left groin refractory to topical treatment. A shave biopsy of the lesion demonstrated non-invasive EMPD which yielded a urology consult. Rather than the standard wide local excision (WLE), which can lead to positive margins, progression, and recurrence, we used a modified the Mohs technique and staged the procedure, providing excellent oncologic and cosmetic outcomes. The described technique has particular merit with uncertain margin status and when geography of lesions preclude a standard Mohs surgery.

Nodular extramammary Paget disease with fibroepitheliomatous hyperplasia.

Extramammary Paget disease (EMPD) is a rare skin condition usually found in the anogenital region. Histologically, EMPD may be associated with varying degrees of epidermal hyperplasia classified as squamous, papillomatous, or fibroepitheliomatous. We report a case of EMPD in a 90-year-old man who presented with well-demarcated plaques and a nodule in the pubic area with fibroepitheliomatous hyperplasia.

Enfermedad de Paget extramamaria / Extramammary Paget's disease

La enfermedad de Paget extramamaria es un carcinoma epidérmico de diferenciación apocrina que se origina en la epidermis o secundario a la diseminación epidermotropa de neoplasias adyacentes o a distancia. Suele presentarse como una lesión eccematiforme, de límites bien definidos, en zonas ricas en glándulas apocrinas como axilas, zona genital y anal. Su pronóstico depende de 2 factores: la profundidad de la invasión del tumor primario y de la presencia o no de tumor asociado. Su sintomatología inespecífica y la lenta evolución de las lesiones a menudo provoca un retraso en el diagnóstico que conlleva un empeoramiento del pronóstico. El diagnóstico de enfermedad de Paget es histológico precisando en ocasiones un estudio inmunohistoquímico. La inmunohistoquímica permite orientar hacia la naturaleza primaria o secundaria de la enfermedad, pero precisará de un estudio de extensión (AU)

Extramammary Paget disease is an epidermal carcinoma with apocrine differentiation originating in the epidermis o secondary to epidermotropic dissemination from a near or distant neoplasm. It usually shows as an eczematiform lesion with well defined margins in areas rich in apocrine glands, such as the axilla, genital and anal areas. Prognosis is defined by two factors: depth of invasion of primary tumour and whether there is an associated tumour. Its non specific clinical signs and slow evolution of the lesions, often delay the diagnosis, which leads to a poor prognosis. The diagnosis of Paget's disease is histological, sometimes requiring an immunohistochemical study. This can orient towards the primary or secondary nature of the disease, but will still need an extension study (AU)

Long-term functional and quality of life outcomes of patients after repair of large perianal skin defects for Paget's and Bowen's disease.

INTRODUCTION: The assessment of long- term functional and quality of life outcomes of these patients following repair of large defects after surgical excision has not been reported. METHODS: Between 1992 and 2004, at two institutions, 18 patients underwent repair of a perianal defect for Paget's disease (n = 8) or Bowen's disease (n = 10) and were alive with intestinal continuity at last follow-up. Patients were mailed the fecal incontinence quality of life scale (FIQL) and the SF-36. RESULTS: Fourteen patients (78%) responded. Median follow-up for responders was 5 years. Mean age was 65 years with 12 females. Subcutaneous skin flaps (11) and split-thickness skin grafts (three) were used to repair the perianal defects, which were circumferential in 11 patients (79%). Nine patients reported incontinence and completed the FIQL. The FIQL scores of patients reporting incontinence were lower for lifestyle, coping/behavior, and embarrassment but not significantly different for depression compared to patients without incontinence. SF-36 scores of the patients were not significantly different from the normative population. CONCLUSION: Functional results after repair of large perianal defects are acceptable and overall quality of life (QOL) is similar to the normative population although a large proportion of patients have some form of incontinence that impacts certain aspects of their QOL.

PIG7/LITAF gene mutation and overexpression of its gene product in extramammary Paget's disease.

To identify cancer-related genes that are involved in the carcinogenesis of extramammary Paget's disease (EMPD), we compared mRNA expression profiles of EMPD lesions and corresponding normal skin using cDNA array. Sixty-eight genes were highly expressed (>5-fold) in EMPD lesions compared to normal skin, and 40 genes were expressed less than one-fifth in EMPD lesions. Among them, PIG7/LITAF mRNA was overexpressed in 3 of 4 EMPD cases. PIG7/LITAF transcription is induced by p53 expression and has been implicated in the p53-induced apoptotic pathway. Since expression of p53 mRNA and p53 protein was not high in any of the 3 EMPD samples compared to the intact skin of the same patient, we analyzed PIG7/LITAF cDNA mutations among 12 EMPD samples (including the former 4) by PCR-SSCP. Three samples showed shifted bands (2 had point mutations leading to amino acid substitutions and 1 had a silent mutation). One sample with amino acid substitution overexpressed PIG7/LITAF mRNA in cDNA array analysis and RT-PCR. PIG7/LITAF mRNA expression is confined to tumor cells in in situ mRNA hybridization analysis. These results indicate that genetic disorder and overexpression of PIG7/LITAF may be involved in EMPD carcinogenesis.

Spontaneous apparent clinical resolution with histologic persistence of a case of extramammary Paget's disease: response to topical 5-fluorouracil.

An 86-year-old woman presented with a 3-year history of an erythematous axillary lesion, which was histologically confirmed to be extramammary Paget's disease (EMPD) confined to the epidermis and adnexa. Surprisingly, spontaneous clinical regression occurred in the lesion, but Paget's cells persisted within the epidermis and adnexa on histologic examination. One year of intermittent topical chemotherapy with 5-fluorouracil resulted in ulcers that were interpreted as EMPD and completely excised. Histologic examination showed a complete absence of Paget's cells. To our knowledge, only one previous report investigated apparent spontaneous clinical resolution with histologic persistence of EMPD. We emphasize that topical 5-fluorouracil cannot be considered a safe treatment modality for EMPD, but it may be useful in certain cases in which the extent of the lesions, or the general condition of the patient, advise against surgery or radiotherapy.

Perianal Paget's disease: a histologic and immunohistochemical study of 11 cases with and without associated rectal adenocarcinoma.

Perianal Paget's disease is rare, and its relationship to an associated internal regional cancer has been ill defined. We analyzed the histologic and immunohistochemical features of perianal Paget's disease in 11 patients to determine the frequency and relationship of associated regional internal carcinoma and to gain insight into its histogenesis. Of five patients with documented rectal adenocarcinoma, it was discovered synchronously with the Paget's disease in four and, subsequently, in one. Paget's cells of signet ring type predominated in four cases. Intraepithelial glands with intraluminal dirty necrosis were present in four cases. The immunophenotype in four cases studied was cytokeratin (CK)7+/CK20+/gross cystic disease fluid protein- (GCDFP) in both the intraepithelial Paget's cells and the invasive rectal adenocarcinoma. Six patients did not have documented rectal carcinoma. The Paget's cells in four were CK7+/CK20-/GCDFP15+. Three of these had purely intraepithelial Paget's disease, and invasive or metastatic disease developed in none after wide local excision. Bilateral inguinal lymph node metastases developed in the fourth patient, and the patient died 8 months after diagnosis of Paget's disease. In two patients, the Paget's cells were CK7+/CK20+/GCDFP15-. Recurrent intraepithelial perianal Paget's disease developed in one patient at 7 months; the patient was alive without disease at 24 months, and the other patient had several intraepithelial recurrences of perianal Paget's disease, and, subsequently, a large perianal tumor of uncertain cell type developed at 108 months, which led to the patient's death. We conclude that there are two types of perianal Paget's disease. One type has endodermal differentiation with gastrointestinal-type glands containing intraluminal dirty necrosis, numerous signet ring cells, CK20 positivity, and GCDFP15 negativity. Such cases are especially likely to be associated with synchronous or metachronous rectal adenocarcinoma. The other type is a primary cutaneous intraepithelial neoplasm in which the Paget's cells display sweat gland differentiation, including GCDFP15 positivity; it generally lacks gastrointestinal-type glands, intraluminal dirty necrosis, and CK20 positivity. The CK7 is a sensitive, albeit nonspecific, marker for Paget's cells.

Enfermedad de Paget extramamaria y mamaria, anaplásica y acantolíca: presentación de 7 casos y revisión de la literatura / Paget disease, extrammamary and mammary, anaplastic, acantholytic: a report of 7 cases and review of the literature

La enfermedad de Paget extramamaria anaplásica y acantolítica (EPeMAA) y la enfermedad de paget mamaria anaplásica y acantolítica (EPMAA), son formas raras de la EP; no se sabe en el momento actual su frecuencia real. Se presentaron por arriba de la cuarta decada, en 4 mujeres y 3 hombres. Su evolución fué crónica, clínicamente fueron placas verrugosas, ulceradas, facilmente sangrantes, bien limitadas. Clínica e histológicamente se confundieron con enfermedad de Bowen y con el pénfigo vegetante. Microscópicamente se observó en todo el espesor de la epidermis células anaplásicas pequeñas, con núcleo ovoide, cromatina fina sin disqueratosis, escaso citoplasma; la acantólisis fué acentuada con formaciones vegetantes. Se observaron células clásicas de Peget en forma alterna; todos exhibieron ulceración y en la periferia la imagen típica de EP. En la base de la neoplásia hubo infiltrado linfocitario en banda "patrón liquenoide". En 4 de los casos se identificó neoplásia maligna sincrónica en la profundidad (1 caso Ca de conductos mamarios, 2 casos Ca de conductos de glándulas apócrina y 1 caso de Ca. de conductos de glándulas ecrina de tipo esclerosante) fueron positivos al antígeno carcinoembrionario (ACE) 5/5, al antígeno de membrana epitelial (AMA) 5/5, y a la citoqueratina de bajo peso molecular (Cqbpm) 5/5. Hay que hacer el diagnóstico diferencial con la enfermedad de Bowen (EB), melanoma de diseminación superficial (MMDS) y con el pénfigo vegete. No hay diferencias en pronóstico entre la EP mamaria y extramamaria clásica y la EPeMAA u EPMAA

Paget's sarcoma of the mandible.

BACKGROUND: Sarcomatous change occurs in less than 1% of patients with Paget's disease. It has been reported in only 9 patients in the mandible, and has been uniformly fatal. Comparison of Paget's sarcoma of the mandible to osteosarcoma of the mandible and to osteosarcoma in other locations was made to attempt to explain and improve the outcome of patients with these tumors. METHODS: Two 78-year-old women with Paget's sarcoma of the mandible treated with radical resection are reported. The literature is reviewed to compare the clinical presentation and prognosis of patients with mandibular Paget's sarcoma to patients with osteosarcoma in non-Pagetoid mandibles and with osteosarcoma outside of the head and neck. RESULTS: Both patients died within 2 years of lung metastases. The patients with mandibular Paget's sarcoma were markedly older, with an average age of 65.6 years, compared to 32.5 years for mandibular osteosarcoma. Paget's sarcoma of the mandible was uniformly rapidly fatal; in non-Pagetoid mandibles the 5-year survival is 40%. There have been reports of only 7 patients who have survived with Paget's sarcoma in other locations. In osteosarcoma of the extremities 5-year disease-free survival exceeds 75% with multimodality therapy. CONCLUSIONS: Paget's sarcoma of the mandible is a rare tumor which affects elderly patients. It progresses rapidly and has a much poorer prognosis than osteosarcoma occurring in a non-Pagetoid mandible. The prognosis may be improved with early detection and treatment with multimodality therapy.

Extramammary Paget's disease: a case study.

Extramammary Paget's Disease is a rare lesion of the genital, axillary or thorax skin that is a counterpart of Paget's Disease of the breast. It is often misdiagnosed as eczema or other skin rashes. The lesion may appear as a red, crusted, sharply demarcated area with submucosal thickening. This case study describes the surgical repair of a perianal wound in a patient with Paget's Disease.

Extramammary Paget's disease: an annotated review.

The incidence, clinical features, histogenesis, and treatment of extramammary Paget's disease (EMPD) are reviewed. This unusual skin lesion is associated with an underlying adnexal neoplasm in about 50% of cases. Also, the incidence of distant organ malignancies of EMPD is higher than expected by chance. Even in the absence of a recognizable underlying cancer, EMPD may occasionally produce distant metastases, indicating the malignant potential of this condition. Histochemical, immunohistological, and lectin binding studies demonstrate that the cell of origin of EMPD is the exocrine cell of sweat glands. Although EMPD may arise from eccrine cells, derivation from apocrine cells appears more common. The treatment of the primary lesion, by wide margin excision, is fraught by a high recurrence rate. Chemosurgery may reduce local relapse of EMPD. The value of adjuvant radiation therapy is unestablished. Chemotherapy has induced remission in 2 cases of advanced EMPD and needs testing in clinical trials.