Extramammary Paget disease (EMPD) is a rare neoplasm with uncertain histogenesis, usually presenting in the anogenital area, most commonly in the vulva. The disease is characterized by slow grow and high recurrence rates. This article reviews the epidemiological, clinical, morphological, genetic and treatment features of EMPD of the vulva reported in recent years.
Extramamární vulvární Pagetova choroba je velmi vzácnou formou tohoto onemocnění, s několika příznaky, jejichž počátečním projevem je výskyt pomalu rostoucího erytematózního plaku v anogenitální oblasti spojeného s pruritem. Vývoj onemocnění je chronický a diagnóza je stanovena často pozdě. Chirurgická excize je hlavní léčebnou metodou a měla by být prováděna se širokým okrajem, vzhledem k vysoké míře lokálních recidiv. Rekonstrukce je často složitá a vyžaduje použití místních nebo vzdálených laloků. Tento text představuje případ 65leté pacientky, která po dobu 2 let trpěla svrběním v oblasti vulvy, měla jasně ohraničenou erytematózní lézi, která nevykazovala žádné zlepšení při lokální léčbě a ze které byla po biopsii potvrzena diagnóza Pagetovy choroby. Po chirurgické excizi byla provedena rekonstrukce pomocí oboustranného myofasciokutánního laloku m. gracilis s vynikajícím estetickým a funkčním výsledkem.
Extramammary vulvar Paget's disease is a very rare presentation of this disease, with few symptoms, whose initial complaint is the appearance of a slow-growing erythematous plaque in the anogenital region associated with pruritus. The evolution is chronic and the diagnosis is often late. Surgical excision is the main treatment and should be performed with wide margins, due to the high rate of local recurrence. Reconstruction is often complex, requiring the use of local or remote flaps. This manuscript presents the case report of a 65-year-old female patient, who had been suffering from pruritus in the vulvar region for 2 years and had a well-defined erythematous lesion, which showed no improvement with topical treatments and that was diagnosed as Paget's disease after biopsy. After surgical excision, reconstruction was performed using bilateral myofasciocutaneous flap of the gracilis muscle, with excellent aesthetic and functional results.
- MeSH
- adenokarcinom chirurgie MeSH
- extramamární Pagetova nemoc * chirurgie patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory vulvy chirurgie MeSH
- vulva chirurgie MeSH
- vulvektomie MeSH
- výsledek terapie MeSH
- zákroky plastické chirurgie * metody MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
BACKGROUND: Primary Extra-mammary Paget's disease (EMPD) is a very rare cutaneous adenocarcinoma affecting anogenital or axillary regions. It is characterized by a prolonged course with recurrences and eventually distant metastatic spread for which no specific therapy is known. METHODS: Eighteen EMPD (13 vulvar and five scrotal) and ten mammary Paget's disease (MPD) cases were comprehensively profiled for gene mutations, fusions and copy number alterations, and for therapy-relevant protein biomarkers). RESULTS: Mutations in TP53 and PIK3CA were the most frequent in both cohorts: 7/15 and 5/15 in EMPD; 1/6 and 4/7 in MPD HER2 gene amplification was detected in 4/18 EMPD (3 vulvar and 1 scrotal case) in contrast to MPD where it was detected in the majority (7/8) of cases. TOP2A gene amplification was seen in 2/12 EMPD and 1/6 MPD, respectively. Similarly, no difference in estrogen receptor expression was seen between the EMPD (4/15) and MPD (3/10). Androgen receptor was also expressed in the majority of both cohorts (12/16 EMPD) and (7/8 MPD).Here ARv7 splice variant was detected in 1/7 EMPD and 1/4 MPD cases, respectively. PD-L1 expression on immune cells was exclusively observed in three vulvar EMPD. In contrast to MPD, six EMPDs harbored a "high" tumor mutation burden (≥10 mutations/Mb). All tested cases from both cohorts were MSI stable. CONCLUSIONS: EMPD shares some targetable biomarkers with its mammary counterpart (steroid receptors, PIK3CA signaling pathways, TOP2A amplification). HER2 positivity is notably lower in EMPD while biomarkers to immune checkpoint inhibitors (high TMB and PD-L1) were observed in some EMPD. Given that no consistent molecular alteration characterizes EMPD, comprehensive theranostic profiling is required to identify individual patients with targetable molecular alterations.
- MeSH
- amplifikace genu MeSH
- cílená molekulární terapie MeSH
- dospělí MeSH
- extramamární Pagetova nemoc farmakoterapie genetika patologie MeSH
- individualizovaná medicína MeSH
- kůže patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikrosatelitní nestabilita MeSH
- mutace MeSH
- nádorové biomarkery antagonisté a inhibitory genetika metabolismus MeSH
- nádory kůže farmakoterapie genetika patologie MeSH
- nádory prsu farmakoterapie genetika patologie MeSH
- Pagetova nemoc prsu farmakoterapie genetika patologie MeSH
- protokoly protinádorové kombinované chemoterapie farmakologie terapeutické užití MeSH
- prsy patologie MeSH
- retrospektivní studie MeSH
- sekvenční analýza DNA MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- skrotum patologie MeSH
- variabilita počtu kopií segmentů DNA MeSH
- vulva patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- MeSH
- extramamární Pagetova nemoc * MeSH
- lidé MeSH
- Pagetova nemoc prsu * MeSH
- vzácné nemoci MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Autoři popisují případ 72leté pacientky s 1 rok trvajícími perianálními erozemi, histologické vyšetření prokázalo sekundární formu extramamární Pagetovy choroby. V diskusi je popsána základní etiologie, patogeneze a diagnostika onemocnění. Základ terapie je radikální chirurgická léčba, ale může se uplatnit radioterapie nebo lokální terapie např. imiquimodem. Prognóza onemocnění je v zásadě dobrá, ale odvíjí se od míry postižení.
The authors describe the case of a 72-year-old female with one-year perianal erosion, histological examination showed a secondary form of extra-mammary Paget's disease. Discussion describes etiology, pathogenesis, and diagnosis of the disease. The basis of therapy is radical surgical treatment, but radiotherapy or local therapies such as imiquimod can be used. The prognosis of the disease is relatively good, but it depends on the stage of the disease.
Extramammary Paget disease (EMPD) is an uncommon intraepithelial malignancy, affecting the vulvo-perineal and perianal region, occurring in 6.5% of all Paget diseases. Usually, an underlying invasive adenocarcinoma denotes a more aggressive behaviour of the disease. We present the multidisciplinary approach in a 75-year old patient with this rare disease. The patient underwent a radical surgical excision and, subsequently, a Singapore flap was used for primary closure. The final histology confirmed the presence of a non-invasive Paget tumor, but a focus of high-grade invasive adenocarcinoma was noted in a perineal nodule. The histological margins were free of tumor. The patient did not undergo any adjuvant treatment because of severe chronic medical problems, although, eighteen months after treatment, she remains well, with no signs of recurrence. In conclusion, radical surgical excision, often necessitating reconstruction techniques, remains the gold standard of care and further adjuvant treatment should be individualised.
- MeSH
- adjuvantní radioterapie MeSH
- extramamární Pagetova nemoc chirurgie patologie radioterapie MeSH
- lidé MeSH
- lokální recidiva nádoru prevence a kontrola MeSH
- nádory anu chirurgie patologie radioterapie MeSH
- nádory vulvy chirurgie patologie radioterapie MeSH
- senioři MeSH
- volné tkáňové laloky * MeSH
- výsledek terapie MeSH
- zákroky plastické chirurgie * MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
To determine whether a subset of primary extramammary Paget disease (EMPD) may originate in anogenital mammary-like glands (AGMLG), the authors studied 181 specimens of EMPD, detailing alterations in AGMLG. The latter were identified in 33 specimens from 31 patients. All patients were women, ranging in age from 38 to 93 years (median, 65 y). In all cases, lesions involved the vulva and in 1 patient the perianal skin was affected. Histopathologically, AGMLG manifested changes identical to columnar cell change (CCC) (87.1%), usual ductal hyperplasia (22.6%), columnar cell hyperplasia (CCH) (9.7%), oxyphilic (apocrine) metaplasia (6.5%), and atypical duct hyperplasia (3.2%). Four cases (12.9%), in addition to intraepidermal carcinoma, harbored invasive carcinoma. In all 4 of these, AGMLG displayed a range of alterations including ductal carcinoma in situ, CCC, and CCH. Three further cases (9.7%) showed ductal carcinoma in situ without any definite invasive carcinoma. Colonization of AGMLG by neoplastic Paget cells was noted in 6 cases. As CCC and CCH may be encountered in normal AGMLG, these alterations are unlikely to play a significant role in the pathogenesis of the disease. However, by analogy with mammary Paget disease, rare cases of primary EMPD may originate in AGMLG with a subsequent upward migration of the neoplastic cells into the epidermis and possible later breach through the basal membrane. Usual ductal hyperplasia and atypical duct hyperplasia can then be regarded as earlier precursor lesions, linking both ends of the spectrum.
- MeSH
- anální kanál patologie MeSH
- dospělí MeSH
- extramamární Pagetova nemoc etiologie patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory anu etiologie patologie MeSH
- nádory vulvy etiologie patologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- vulva patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Mammary-like glands are a normal anatomical component of the anogenital region and can give rise to many benign and malignant tumors that morphologically mimic the similar diseases of the breast. The literature review is complemented by a description of 199 cases of malignant tumors of mammary-like glands. The paper presents the clinical and morphological characteristics of various malignant tumors of mammary-like glands, including extramammary Paget's disease, ductal, tubulolobular, adenoid cystic adenocarcinoma, low-grade phyllodes tumor, etc.
- MeSH
- aktinická keratóza etiologie patologie MeSH
- arsenikové přípravky škodlivé účinky MeSH
- dehty škodlivé účinky terapeutické užití MeSH
- diferenciální diagnóza MeSH
- extramamární Pagetova nemoc epidemiologie patologie MeSH
- keratóza etiologie patologie MeSH
- leukoplakie diagnóza epidemiologie MeSH
- nádory duktální, lobulární a medulární klasifikace patologie MeSH
- prekancerózy * klasifikace patologie MeSH
Anogenital mammary-like glands (AGMLGs) are nowadays considered a normal component of the anogenital area. Lesions involving AGMLGs are histopathologically very similar to their mammary counterparts, but the information on molecular biological mechanisms in these vulvar/perianal tumors is scarce. Mutations in the PI3K-AKT cascade have been found in hidradenoma papilliferum. The authors studied selected BRCA1, BRCA2, and PIK3CA mutations in series of benign and malignant neoplasms thought to be associated with AGMLGs, including 9 cases of primary extramammary Paget disease, 3 different cases of mammary-type carcinoma (adenoid cystic like, tubulolobular, and invasive ductal like), and 5 cases of hidradenoma papilliferum. No BRCA mutation was detected, whereas 3 neoplasms yielded PIK3CA mutation, including extramammary Paget disease, mammary-type invasive ductal carcinoma, and tubulolobular carcinoma. Our study expands the spectrum of lesions of AGMLGs harboring mutations in genes encoding the PI3K-AKT cascade. Further studies of the whole BRCA1 and BRCA2 genes using a larger cohort are needed to clarify their role in the pathogenesis of AGMLG lesions.
- MeSH
- extramamární Pagetova nemoc genetika patologie MeSH
- fosfatidylinositol-3-kinasy třídy I genetika MeSH
- hodnocení rizik MeSH
- imunohistochemie MeSH
- jehlová biopsie MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mléčné žlázy lidské patologie MeSH
- mutace MeSH
- nádory anu genetika patologie MeSH
- nádory vulvy genetika patologie MeSH
- prognóza MeSH
- protein BRCA1 genetika MeSH
- protein BRCA2 genetika MeSH
- regulace genové exprese u nádorů MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
