The role of sentinel lymph node biopsy in the management of invasive extramammary Paget's disease: Multi-center, retrospective study of 151 patients

Fujisawa, Yasuhiro; Yoshino, Koji; Kiyohara, Yoshio; Kadono, Takafumi; Murata, Yozo; Uhara, Hisashi; Hatta, Naohito; Uchi, Hiroshi; Matsushita, Satoru; Takenouchi, Tatsuya; Hayashi, Toshihiko; Fujimoto, Manabu; Ohara, Kuniaki

doi:10.1016/j.jdermsci.2015.03.014

Cited by 66 publications

(40 citation statements)

References 17 publications

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“…12 Once it invades dermis and deep structures, the risk of lymph node and distant metastases significantly increases. 13,14 Due to its rarity, no systemic, comprehensive evaluation of targeted therapies has been performed. Selected cases of EMPD (with amplified ERBB2/HER2 gene) have been successfully treated with trastuzumab alone or in combinations with chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the biomarkers for targeted therapies in primary extra‐mammary and mammary Paget's disease

et al. 2020

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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.

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Section: Discussionmentioning

confidence: 99%

Comparison of the biomarkers for targeted therapies in primary extra‐mammary and mammary Paget's disease

et al. 2020

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“…22 Fujisawa et al noted that SLN biopsy is inappropriate for clinically enlarged lymph nodes. 26 Hatta et al found lymph node metastasis in only four out of eight lymph node swelling cases. 18 Another study showed positivity in four out of seven patients.…”

Section: Discussionmentioning

confidence: 95%

“…Fujisawa et al . noted that SLN biopsy is inappropriate for clinically enlarged lymph nodes . Hatta et al .…”

Section: Discussionmentioning

confidence: 99%

Evaluation of positron emission tomography imaging to detect lymph node metastases in patients with extramammary Paget's disease

Fujiwara

Suzuki

Senoo

et al. 2017

The Journal of Dermatology

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Patients with extramammary Paget's disease (EMPD) have a relatively good prognosis, when spread of the tumor cells is limited to the epidermis. However, invasive EMPD has a poor prognosis, when the patients have regional lymph node metastasis. Detection of nodal metastasis is thus mandatory to manage EMPD. To evaluate the F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging to assess lymph node metastasis, 15 patients with histologically proven primary EMPD were enrolled in this study. All patients underwent whole-body PET prior to sentinel lymph node biopsy (SLNB). The maximum standardized uptake value (SUVmax) of more than 2.5 was evaluated as positive PET indicative of malignancy. Among 14 cases with the primary genital lesions, 11 cases underwent bilateral SLNB of the inguinal nodal basin and the remaining three cases unilateral SLNB. One case with a primary axillary lesion underwent unilateral SLNB of the axillary nodal basin. Therefore, a total of 26 regional basins were investigated. In general, nodal basins can be categorized into four groups: (i) histologically negative and PET negative (true negative); (ii) histologically positive and PET negative (false negative); (iii) histologically positive and PET positive (true positive); and (iv) histologically negative and PET positive (false positive) groups. In the 26 nodal basins, there were 19 true negative and seven true positive cases, and neither false negative nor false positive cases were observed. The mean SUVmax was significantly higher in the true positive basins (8.03 ± 3.34) than in the true negative basins (0.26 ± 0.56). The SUVmax value may be useful for detection of nodal metastasis.

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“…22 On the other hand, for early EMPD management with no clinical evidence of nodal metastases, some authors have suggested the use of sentinel lymph node (SLN) biopsy. [10][11][12] This suggests that a significant proportion of patients with no initial clinical evidence of nodal metastases may harbor clinically silent micrometastases, and confirmation of lymph node disease by SLN biopsy or imaging can help determine treatment strategy. Nevertheless, the impact of SLN biopsy on prognosis has not yet been established.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, the impact of SLN biopsy on prognosis has not yet been established. 11 In addition, consensus regarding the site of tracer administration has not been established and further investigation is required.…”

Section: Discussionmentioning

confidence: 99%

Outcomes of lymph node dissection in the treatment of extramammary Paget’s disease: A single‐institution study

Tsutsui

Takahashi²,

Muto³

et al. 2020

The Journal of Dermatology

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Extramammary Paget's disease (EMPD) often invades the dermis and metastasizes to the lymph nodes. Patients with EMPD associated with lymph node metastases have poor prognosis; to date, effective treatment has not yet been established. Lymph node dissection, aiming to control the local disease, is a standard form of management for EMPD patients with lymph node metastases (LNM). We investigated the clinical and pathological features, treatment strategies and prognostic factors of patients with metastatic EMPD who underwent lymph node dissection. We retrospectively evaluated 38 cases of extramammary Paget's disease with lymph node metastasis over 10 years. All patients underwent wide resection of the primary lesion and lymph node dissection. Univariate analysis revealed the number of metastatic nodes and lymphadenopathy as prognostic factors. In multivariate analysis, the number of metastatic lymph nodes retained statistical significance (hazard ratio, 35.3; 95% confidence interval, 3.23-387.0; P = 0.003). The 5-year survival rate was 100% and 19.1% in patients with two or less LNM and with three or more LNM, respectively. In patients with three or more LNM, the 5-year survival rate after adjuvant radiation therapy was better than that after surgery alone (75% vs 0%). In conclusion, patients with two or less LNM can be expected to have long-term survival with lymph node dissection only, while patients with three or more LNM may require adjuvant radiation therapy to improve prognosis. These results suggest that lymph node dissection may be a strategy to treat EMPD with regional LNM. METHODS PatientsThis retrospective analysis examined a prospectively maintained database of 89 EMPD patients with dermal invasion who were treated at

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The role of sentinel lymph node biopsy in the management of invasive extramammary Paget's disease: Multi-center, retrospective study of 151 patients

Cited by 66 publications

References 17 publications

Comparison of the biomarkers for targeted therapies in primary extra‐mammary and mammary Paget's disease

Comparison of the biomarkers for targeted therapies in primary extra‐mammary and mammary Paget's disease

Evaluation of positron emission tomography imaging to detect lymph node metastases in patients with extramammary Paget's disease

Outcomes of lymph node dissection in the treatment of extramammary Paget’s disease: A single‐institution study

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