Skip to main content

Main menu

  • Home
  • Current Issue
  • Archive
  • Info for
    • Authors
    • Advertisers
    • Editorial Board
  • Other Publications
    • Anticancer Research
    • Cancer Genomics & Proteomics
    • Cancer Diagnosis & Prognosis
  • More
    • IIAR
    • Conferences
  • About Us
    • General Policy
    • Contact
  • Other Publications
    • In Vivo
    • Anticancer Research
    • Cancer Genomics & Proteomics

User menu

  • Register
  • Subscribe
  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
In Vivo
  • Other Publications
    • In Vivo
    • Anticancer Research
    • Cancer Genomics & Proteomics
  • Register
  • Subscribe
  • My alerts
  • Log in
  • My Cart
In Vivo

Advanced Search

  • Home
  • Current Issue
  • Archive
  • Info for
    • Authors
    • Advertisers
    • Editorial Board
  • Other Publications
    • Anticancer Research
    • Cancer Genomics & Proteomics
    • Cancer Diagnosis & Prognosis
  • More
    • IIAR
    • Conferences
  • About Us
    • General Policy
    • Contact
  • Visit iiar on Facebook
  • Follow us on Linkedin
Research ArticleClinical Studies

Perineural Invasion Correlates With Common Pathological Variables and Clinical Outcomes of Patients With Squamous Cell Carcinoma of the Vulva Treated With Primary Radical Surgery and Inguinal-femoral Lymphadenectomy

ANGIOLO GADDUCCI, SABINA PISTOLESI, STEFANIA COSIO, CHIARA COMUNALE, ANTONIO FANUCCHI and ANTONIO GIUSEPPE NACCARATO
In Vivo March 2021, 35 (2) 1051-1056; DOI: https://doi.org/10.21873/invivo.12349
ANGIOLO GADDUCCI
1Department of Clinical and Experimental Medicine, Division of Gynecology and Obstetrics, University of Pisa, Pisa, Italy;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: a.gadducci@med.unipi.it
SABINA PISTOLESI
2Department of New Technologies and Translational Research, Division of Pathology, University of Pisa, Pisa, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
STEFANIA COSIO
1Department of Clinical and Experimental Medicine, Division of Gynecology and Obstetrics, University of Pisa, Pisa, Italy;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
CHIARA COMUNALE
1Department of Clinical and Experimental Medicine, Division of Gynecology and Obstetrics, University of Pisa, Pisa, Italy;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
ANTONIO FANUCCHI
1Department of Clinical and Experimental Medicine, Division of Gynecology and Obstetrics, University of Pisa, Pisa, Italy;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
ANTONIO GIUSEPPE NACCARATO
2Department of New Technologies and Translational Research, Division of Pathology, University of Pisa, Pisa, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

Background/Aim: The aims of the study were: i) to assess the incidence of perineural invasion (PNI) in squamous cell carcinoma of the vulva and ii) to correlate PNI with common pathological prognostic variables and clinical outcome of patients. Patients and Methods: The hospital records of 64 patients with vulvar squamous cell carcinoma who underwent primary radical surgery were reviewed. Results: PNI was significantly related to stage (p=0.038), size (p=0.038), lymph-vascular space involvement (p=0.013) and nodal status (p=0.038), but not to patient age, tumor grade and stromal invasion. Five-year disease-free survival was 30.0% in patients with PNI and 53.1% in those without PNI (p=0.018), and the corresponding 5-year overall survival was 50.0% and 77.1% (p=0.031), respectively. Conclusion: PNI was associated with common pathological prognostic variables and with a poorer clinical outcome in patients with vulvar squamous cell carcinoma.

  • Perineural invasion
  • vulvar squamous cell carcinoma
  • radical vulvectomy
  • inguinal-femoral-lymphadenectomy
  • recurrence

The GLOBOCAN 2018 database, which has estimated the worldwide incidence and mortality for 36 cancers in 185 countries, reported 44.235 new cases of vulvar carcinoma and 15.222 deaths due to malignancy in 2018 (1). Squamous cell carcinoma is the most common histological type, with an age-related incidence ranging from 0.4:100,000 among women in their thirties to 20:100,000 among women older than 70 years old (2). Surgery is the cornerstone of treatment for most tumors, and includes deep partial or total vulvectomy with bilateral inguinal-femoral lymphadenectomy or sentinel node biopsy in selected cases (3-8). Lymph nodal status is the strongest prognostic variable, with 5-year overall survival (OS) rates ranging from 70% to 98% for patients with negative nodes to 12% to 41% for those with positive nodes. Also, the number, the size, and growth pattern of nodal metastases as well as tumor stage, tumor grade, stromal invasion and lymph vascular space involvement (LVSI) impact on the clinical outcome (2, 9, 10). Patients with locally advanced disease can be treated with ultra-radical surgery, radiotherapy, definitive concurrent chemo-radiation or concurrent chemo-radiation followed by individualized surgery, but there are no well-defined guidelines for this clinical setting (11-13). Postoperative adjuvant inguinal and pelvic radiotherapy is warranted after radical surgery and inguinal-femoral lymphadenectomy in patients with more than one intranodal metastasis or with extra-nodal tumor growth (5-7).

Perineural invasion (PNI) has been found to correlate with a high loco-regional recurrence rate and an unfavorable clinical outcome in several malignancies (14-19). On the other hand, a few data are currently available on the biological and clinical relevance of PNI in surgically-treated patients with squamous cell carcinoma of the vulva (20-24).

The aims of the present retrospective investigation were: i) to assess the incidence of PNI in surgical samples of patients with vulvar squamous cell carcinoma who underwent primary radical surgery and inguinal-femoral lymphadenectomy and ii) to correlate PNI with common pathological prognostic factors, disease-free survival (DFS) and OS.

Patients and Methods

This retrospective study was conducted on 64 patients with squamous cell carcinoma of the vulva who underwent primary deep partial or total vulvectomy and inguinal-femoral lymphadenectomy at the Department of Gynecology and Obstetrics of the University of Pisa between January 2006 and July 2019. Patients who underwent surgery without lymphadenectomy because of stage Ia1 disease or poor performance status as well as those who received primary chemo-radiation followed by individualized surgery for locally advanced disease were not included in the present analysis.

The surgical treatment of the vulva was classified according to the glossary of terminology proposed by Micheletti et al. (4). The surgical excision encompassed the lesion with a free margin of at least 1 cm of clinically normal skin, and removed a portion of the vulva in all its thickness from the surface to the urogenital diaphragm. Deep partial vulvectomy indicated that the vulvar excision was limited to a portion of the vulva, whereas deep total vulvectomy denoted the removal of the whole vulva.

Deep partial vulvectomy was usually performed in patients with T1 disease when the lesion was unifocal and the remainder of the vulva was normal. Deep total vulvectomy was the standard treatment for patients with T1 tumor and with multifocal disease or widespread intraepithelial vulvar neoplasia or lichen sclerosus as well as for those with more advanced tumor.

The tumor stage of each case was retrospectively determined according to the criteria of the International Federation of Gynecology and Obstetrics (FIGO) 2009 (25).

The histological samples were reviewed by two pathologists (S.P. e G.N.). PNI was defined as the presence of tumor cells within any of the three layers of the nerve sheath or as the presence of tumor in close proximity to a nerve and involving at least one-third of the nerve’s circumference (26). An immuno-histochemical staining with the S100 antibody was often used to detect nerve tissues (21-23, 27-29).

Postoperative management was individually established by a multidisciplinary team on the basis of histological findings on surgical specimens, patient age and general conditions, after an exhaustive discussion with the patient herself. Adjuvant external beam irradiation was usually administered to patients with more than one intra-nodal metastasis or with extra-nodal tumor growth. Irradiation field usually encompassed groin, obturator, external and internal iliac areas and primary tumor bed, and patients received a total dose of 45-50 Gy in 5-6.5 weeks. Concomitant weekly cisplatin 40 mg/m2 was added to radiotherapy in some cases. Follow-up data were available for 60 patients. The median follow-up of survivors was 33 months (range=9-133 months).

Statistical methods. The SAS statistical package (release 8.2, SAS Institute, Cary, NC, USA) was used for the computations. PNI was compared to the common pathological variables using Fisher’s exact test. Recurrence rates were compared to the prognostic variables using Fisher’s exact test. The time from surgery to first recurrence or death for any cause without recurrence was defined as DFS, and the time from surgery to death or last observation was defined as OS. The cumulative probability of DFS and OS was estimated by the product-limit method. The log-rank test was used to compare the homogeneity of DFS and OS functions across strata defined by categories of prognostic variables.

Results

The surgical treatment consisted of deep total vulvectomy in 49 (76.6%) and partial deep vulvectomy in 15 (23.4%) patients. Inguinal-femoral lymphadenectomy was bilateral in 52 (81.25%) and unilateral in 12 (18.75%) patients. The median age of women was 72 years (range=35-88 years).

FIGO stage was I in 38 (59.4%), II in 1 (1.6%), IIIa in 5 (7.8%), IIIb in 6 (9.4%) and IIIc in 14 (21.9%) patients, respectively. Tumor grade was well differentiated in 12 (18.7%), moderately differentiated in 22 (34.4%) and poorly differentiated in 30 (46.9%) patients. Tumor size was ≤2 cm in 22 (34.4%) and >2 cm in 42 (65.6%), deep stromal invasion was ≤5 mm in 32 (50.0%) and >5 mm in 32 (50.0%), and LVSI was present in 22 (34.4%) and absent in 42 (65.6%) cases, respectively. PNI was detected in 16 (25.0%) patients. Histologically assessed groin nodes were positive in 25 (39.1%) and negative in 39 (60.9%) patients, respectively. Among the 25 patients with metastatic groin nodes, 9 (36.0%) had one positive node and 16 (64.0%) had two or more positive nodes.

PNI was significantly related to tumor stage (p=0.038), tumor size (p=0.038), LVSI (p=0.013) and nodal status (p=0.038), but not to patient age, tumor grade and stromal invasion (Table I).

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table I.

Correlation between perineural infiltration and common prognostic variables.

Follow-up data were available for 60 patients. Nine and five patients underwent adjuvant radiotherapy and adjuvant cisplatin–based concurrent chemo-radiation, respectively. One patient received adjuvant chemotherapy with cisplatin 50 mg/m2+paclitaxel 175 mg/m2 every 3 weeks for 5 cycles for the presence of 9 histologically proven positive groin nodes and extensive LVSI on the surgical samples.

Twenty-six (43.3%) patients relapsed after a median time of 16 months (range=3-122 months). The failure was local only in 13 patients (50.0%), inguinal in 9 (34.6%) (associated with local recurrence in 5 cases) and distant in 4 (15.4%) (associated with groin recurrence in 2 cases). The recurrence rate significantly correlated with tumor stage (p=0.036), LVSI (p=0.050), nodal status (p=0.036) and PNI (p=0.014) (Table II). It is worth noting that inguinal and/or distant failure developed in 8 of the 15 (53.3%) patients with PNI versus 5 of the 45 (11.1%) patients without PNI (p=0.001).

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table II.

Recurrence rate by prognostic variables.

DFS was significantly related to patient age (p=0.006), tumor stage (p=0.005), LVSI (p=0.001), nodal status (p=0.002) and PNI (p=0.018) (Table III) (Figure 1).

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table III.

Variables predictive of disease--free survival.

Figure 1.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 1.

Disease-free survival by perineural invasion.

At present, 29 (48.3%) patients are alive with no evidence of tumor, 8 (13.3%) are alive with tumor, 18 (30.0%) died of tumor, and 5 (8.3%) died of intercurrent disease with no evidence of tumor.

OS was significantly related to patient age (p=0.001), tumor stage (p=0.002), LVSI (p<0.0001), nodal status (p=0.001) and PNI (p=0.031) (Table IV, Figure 2).

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table IV.

Variables predictive of overall survival.

Figure 2.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 2.

Overall survival by perineural invasion.

Discussion

PNI has been detected in 7.6-52.4% of patients with squamous cell carcinoma of the vulva (20-24, 29). In the present study PNI was found in 25.0% of 64 surgical specimens of primary deep partial or total vulvectomy and inguinal-femoral lymphadenectomy. In agreement with the literature, this variable was significantly associated with large tumor size (22), advanced tumor stage (24), LVSI (22, 24) and nodal involvement (22, 24, 30).

In the study of Long et al. (22) including 105 patients, PNI correlated with a higher risk of recurrence and death at univariate analysis [hazard ratio (HR)=2.93, 95% confidence interval (CI)=1.20-7.34, and HR=3.04, 95%CI=1.19-7.72, respectively] but not at multivariate analysis. Similar conclusions have been reported by a Spanish study on 43 patients (20). An investigation of Holthoff et al. (21) has found that PNI was present in 67.7% of the 31 tumors that relapsed versus 42.8% of the 63 tumors that did not (p=0.0290). PNI was associated with 1.64-fold higher risk and 2.74-fold-higher risk of recurrence and 2.71-fold higher risk and 4.93-fold higher risk of death, respectively, in the series of Salcedo et al. (24) including 421 patients and in the series of Ferrari at al. (23) including 74 patients. In the present investigation, PNI was significantly related to overall recurrence rate (p=0.014), inguinal and/or distant recurrence rate (p=0.001), DFS (p=0.018) and OS (p=0.031) at univariate analysis.

Our study confirms that PNI correlates with the common pathological prognostic variables and with the clinical outcome of patients with squamous cell carcinoma of the vulva who underwent primary radical surgery. This finding should be assessed routinely in the surgical specimens and could be taken into consideration when planning adjuvant treatment (21-24, 29).

Footnotes

  • Authors’ Contributions

    Conceptualization, Writing - original draft: AG; Data curation, Formal analysis, Methodology, Writing-review & editing: AG, SB, SC, CC, AF, AGN.

  • This article is freely accessible online.

  • Conflicts of Interest

    The Authors declare no conflicts of interest in relation to this study.

  • Received October 23, 2020.
  • Revision received November 24, 2020.
  • Accepted November 26, 2020.
  • Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved

References

  1. ↵
    1. Bray F,
    2. Ferlay J,
    3. Soerjomataram I,
    4. Siegel RL,
    5. Torre LA and
    6. Jemal A
    : Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68: 394-424, 2018. PMID: 30207593. DOI: 10.3322/caac.21492
    OpenUrlCrossRefPubMed
  2. ↵
    1. Gadducci A,
    2. Tana R,
    3. Barsotti C,
    4. Guerrieri ME and
    5. Genazzani AR
    : Clinico-pathological and biological prognostic variables in squamous cell carcinoma of the vulva. Crit Rev Oncol Hematol 83: 71-83, 2012. PMID: 22015047. DOI: 10.1016/j.critrevonc.2011.09.003
    OpenUrlCrossRefPubMed
  3. ↵
    1. Homesley HD
    : Management of vulvar cancer. Cancer 76: 2159-2170, 1995. PMID: 8635016. DOI: 10.1002/1097-0142(19951115)76:10+<2159::aid-cncr2820761341>3.0.co;2-8
    OpenUrlCrossRefPubMed
  4. ↵
    1. Micheletti L,
    2. Preti M,
    3. Zola P,
    4. Zanotto Valentino MC,
    5. Bocci C and
    6. Bogliatto F
    : A proposed glossary of terminology related to the surgical treatment of vulvar carcinoma. Cancer 83: 1369-1375, 1998. PMID: 9762938.
    OpenUrlPubMed
  5. ↵
    1. Gadducci A,
    2. Cionini L,
    3. Romanini A,
    4. Fanucchi A and
    5. Genazzani AR
    : Old and new perspectives in the management of high-risk, locally advanced or recurrent, and metastatic vulvar cancer. Crit Rev Oncol Hematol 60: 227-241, 2006. PMID: 16945551. DOI: 10.1016/j.critrevonc.2006.06.009
    OpenUrlCrossRefPubMed
    1. Oonk MHM,
    2. Planchamp F,
    3. Baldwin P,
    4. Bidzinski M,
    5. Brännström M,
    6. Landoni F,
    7. Mahner S,
    8. Mahantshetty U,
    9. Mirza M,
    10. Petersen C,
    11. Querleu D,
    12. Regauer S,
    13. Rob L,
    14. Rouzier R,
    15. Ulrikh E,
    16. van der Velden J,
    17. Vergote I,
    18. Woelber L and
    19. van der Zee AGJ
    : European Society of Gynaecological Oncology guidelines for the management of patients with vulvar cancer. Int J Gynecol Cancer 27: 832-837, 2017. PMID: 28441255. DOI: 10.1097/IGC.0000000000000975
    OpenUrlAbstract/FREE Full Text
  6. ↵
    1. Koh WJ,
    2. Greer BE,
    3. Abu-Rustum NR,
    4. Campos NR,
    5. Cho KR,
    6. Chon HS,
    7. Chu C,
    8. D. Cohn D,
    9. Crispens MA,
    10. Dizon DS,
    11. Dorigo O,
    12. Eifel PJ,
    13. Fisher CM,
    14. P. Frederick P,
    15. Gaffney DK,
    16. Han E,
    17. Higgins S,
    18. Huh WK,
    19. Lurain JR , 3rd,
    20. Mariani A,
    21. Mutch D,
    22. Nagel C,
    23. Nekhlyudov L,
    24. Fader AN,
    25. Remmenga SW,
    26. Tillmanns T,
    27. Ueda S,
    28. Valea FA,
    29. Wyse E,
    30. Yashar CM,
    31. McMillian N and
    32. Scavone J
    : Vulvar cancer, version 1.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 15: 92-120, 2017. PMID: 28040721. DOI: 10.6004/jnccn.2017.0008
    OpenUrlAbstract/FREE Full Text
  7. ↵
    1. Te Grootenhuis NC,
    2. van der Zee AG,
    3. van Doorn HC,
    4. van der Velden J,
    5. Vergote I,
    6. Zanagnolo V,
    7. Baldwin PJ,
    8. Gaarenstroom KN,
    9. van Dorst EB,
    10. Trum JW,
    11. Slangen BF,
    12. Runnebaum IB,
    13. Tamussino K,
    14. Hermans RH,
    15. Provencher DM,
    16. de Bock GH,
    17. de Hullu JA and
    18. Oonk MH
    : Sentinel nodes in vulvar cancer: Long-term follow-up of the GROningen INternational Study on Sentinel nodes in Vulvar cancer (GROINSS-V) I. Gynecol Oncol 140: 8-14, 2016. PMID: 26428940. DOI: 10.1016/j.ygyno.2015.09.077
    OpenUrlCrossRefPubMed
  8. ↵
    1. Hacker NF,
    2. Eifel PJ and
    3. van der Velden J
    : Cancer of the vulva. Int J Gynecol Obstet 131: S76-S83, 2015. PMID: 26433678. DOI: 10.1016/j.ijgo.2015.06.002
    OpenUrlCrossRef
  9. ↵
    1. Polterauer S,
    2. Schwameis R,
    3. Grimm C,
    4. Hillemanns P,
    5. Jückstock J,
    6. Hilpert F,
    7. de Gregorio N,
    8. Hasenburg A,
    9. Sehouli J,
    10. Fürst ST,
    11. Strauß HG,
    12. Baumann K,
    13. Thiel F,
    14. Mustea A,
    15. Harter P,
    16. Wimberger P,
    17. Kölbl H,
    18. Reinthaller A,
    19. Woelber L and
    20. Mahner S
    : Lymph node ratio in inguinal lymphadenectomy for squamous cell vulvar cancer: Results from the AGO-CaRE-1 study. Gynecol Oncol 153: 286-291, 2019. PMID: 30760408. DOI: 10.1016/j.ygyno.2019.02.007
    OpenUrlCrossRef
  10. ↵
    1. Hoffman MS
    : Squamous-cell carcinoma of the vulva: locally advanced disease. Best Pract Res Clin Obstet Gynaecol 17: 635-647, 2003. PMID: 12965136. DOI: 10.1016/s1521-6934(03)00051-8
    OpenUrlCrossRefPubMed
    1. O’Donnell RL,
    2. Verleye L,
    3. Ratnavelu N,
    4. Galaal K and
    5. Fisher A
    : Locally advanced vulva cancer: A single centre review of anovulvectomy and a systematic review of surgical, chemotherapy and radiotherapy alternatives. Is an international collaborative RCT destined for the “too difficult to do” box? Gynecol Oncol 144: 438-447, 2017. PMID: 28034465. DOI: 10.1016/j.ygyno.2016.12.007
    OpenUrlCrossRef
  11. ↵
    1. Gadducci A and
    2. Aletti GD
    : Locally advanced squamous cell carcinoma of the vulva: A challenging question for gynecologic oncologists. Gynecol Oncol 158: 208-217, 2020. PMID: 32460996. DOI: 10.1016/j.ygyno.2020.05.021
    OpenUrlCrossRef
  12. ↵
    1. Carter JB,
    2. Johnson MM,
    3. Chua TL,
    4. Karia PS and
    5. Schmults CD
    : Outcomes of primary cutaneous squamous cell carcinoma with perineural invasion: an 11-year cohort study. JAMA Dermatol 149: 35-41, 2013. PMID: 23324754. DOI: 10.1001/jamadermatol.2013.746
    OpenUrlCrossRefPubMed
    1. Cui L,
    2. Shi Y and
    3. Zhang GN
    : Perineural invasion as a prognostic factor for cervical cancer: a systematic review and meta-analysis. Arch Gynecol Obstet 292: 13-19, 2015. PMID: 25637504. DOI: 10.1007/s00404-015-3627-z
    OpenUrlCrossRef
    1. Furuhashi S,
    2. Sakaguchi T,
    3. Murakami T,
    4. Fukushima M4,
    5. Morita Y,
    6. Ikegami K,
    7. Kikuchi H,
    8. Setou M and
    9. Takeuchi H
    : Tenascin C in the tumor-nerve microenvironment enhances perineural invasion and correlates with locoregional recurrence in pancreatic ductal adenocarcinoma. Pancreas 49: 442-454, 2020. PMID: 32132519. DOI: 10.1097/MPA.0000000000001506
    OpenUrlCrossRef
    1. Zhao B,
    2. Lv W,
    3. Mei D,
    4. Luo R,
    5. Bao S,
    6. Huang B and
    7. Lin J
    : Perineural invasion as a predictive factor for survival outcome in gastric cancer patients: a systematic review and meta-analysis. J Clin Pathol 73: 544-551, 2020. PMID: 31980559. DOI: 10.1136/jclinpath-2019-206372
    OpenUrlAbstract/FREE Full Text
    1. Kim S,
    2. Huh JW,
    3. Lee WY,
    4. Yun SH,
    5. Kim HC,
    6. Cho YB,
    7. Park YA and
    8. Shin JK
    : Lymphovascular invasion, perineural invasion, and tumor budding are prognostic factors for stage I colon cancer recurrence. Int J Colorectal Dis 35: 881-885, 2020. PMID: 32112198. DOI: 10.1007/s00384-020-03548-4
    OpenUrlCrossRef
  13. ↵
    1. Zhu J,
    2. Zhou R,
    3. Wang Y and
    4. Yu M
    : Perineural invasion as a prognostic factor in head and neck squamous cell carcinoma: a systematic review and meta-analysis. Acta Otolarynol 139: 1038-1043, 2019. PMID: 31464544. DOI: 10.1080/00016489.2019.1655167
    OpenUrlCrossRef
  14. ↵
    1. Lerma E,
    2. Matias-Guiu X,
    3. Lee SJ and
    4. Prat J
    : Squamous cell carcinoma of the vulva: study of ploidy, HPV, p53, and pRb. Int J Gynecol Pathol 18: 191-197, 1999. PMID: 12090585. DOI: 10.1097/00004347-199907000-00001
    OpenUrlCrossRefPubMed
  15. ↵
    1. Holthoff ER,
    2. Jeffus SK,
    3. Gehlot A,
    4. Stone R,
    5. Erickson SW,
    6. Kelly T,
    7. Quick CM and
    8. Post SR
    : Perineural invasion is an independent pathologic indicator of recurrence in vulvar squamous cell carcinoma. Am J Surg Pathol 39: 1070-1074, 2015. PMID: 25786085. DOI: 10.1097/PAS.0000000000000422
    OpenUrlCrossRef
  16. ↵
    1. Long Y,
    2. Yao DS,
    3. Wei YS,
    4. Wei CH and
    5. Chen XY
    : Prognostic significance of perineural invasion in vulvar squamous cell carcinoma. Cancer Manag Res 11: 4461-4469, 2019. PMID: 31191008. DOI: 10.2147/CMAR.S198047
    OpenUrlCrossRef
  17. ↵
    1. Ferrari F,
    2. Forte S,
    3. Ardighieri L,
    4. Bonetti E,
    5. Fernando B,
    6. Sartori E and
    7. Odicino F
    : Multivariate analysis of prognostic factors in primary squamous cell vulvar cancer: The role of perineural invasion in recurrence and survival. Eur J Surg Oncol 45: 2115-2119, 2019. PMID: 31378417. DOI: 10.1016/j.ejso.2019.07.029
    OpenUrlCrossRef
  18. ↵
    1. Salcedo MP,
    2. Sood AK,
    3. Dos Reis R,
    4. Ramalingam P,
    5. Chen C,
    6. Frumovitz M,
    7. Jhingran A,
    8. Pitcher B,
    9. Ramirez PT and
    10. Schmeler KM
    : Perineural invasion (PNI) in vulvar carcinoma: a review of 421 cases. Gynecol Oncol 152: 101-105, 2019. PMID: 30396690. DOI: 10.1016/j.ygyno.2018.10.035
    OpenUrlCrossRef
  19. ↵
    1. Hacker NF
    : Revised FIGO staging for carcinoma of the vulva. Int J Gynaecol Obstet 105: 105-106, 2009. PMID: 19329116. DOI: 10.1016/j.ijgo.2009.02.011
    OpenUrlCrossRefPubMed
  20. ↵
    1. Liebig C,
    2. Ayala G,
    3. Wilks JA,
    4. Berger DH and
    5. Albo D
    : Perineural invasion in cancer: a review of the literature. Cancer 115: 3379-3391, 2009. PMID: 19484787. DOI: 10.1002/cncr.24396
    OpenUrlCrossRefPubMed
  21. ↵
    1. Kurtz KA,
    2. Hoffman HT,
    3. Zimmerman MB and
    4. Robinson RA
    : Perineural and vascular invasion in oral cavity squamous carcinoma: increased incidence on re-review of slides and by using immunohistochemical enhancement. Arch Pathol Lab Med 129: 354-3519, 2005. PMID: 15737030. DOI: 10.1043/1543-2165(2005)129<354:PAVIIO>2.0.CO;2
    OpenUrlCrossRefPubMed
    1. Shimada Y,
    2. Kido T,
    3. Kameyama H,
    4. Nakano M,
    5. Yagi R,
    6. Tajima Y,
    7. Okamura T,
    8. Nakano M,
    9. Nagahashi M,
    10. Kobayashi T,
    11. Minagawa M,
    12. Kosugi S,
    13. Wakai T and
    14. Ajioka Y
    : Clinical significance of perineural invasion diagnosed by immunohistochemistry with anti-S100 antibody in Stage I-III colorectal cancer. Surg Today 45: 1493-1500, 2015. PMID: 25502403. DOI: 10.1007/s00595-014-1096-9
    OpenUrlCrossRef
  22. ↵
    1. Gadducci A,
    2. Pistolesi S,
    3. Cosio S and
    4. Naccarato AG
    : Is perineural invasion a novel prognostic factor useful to tailor adjuvant treatment in patients treated with primary surgery for cervical and vulvar carcinoma? Anticancer Res 40: 3031-3037, 2020. PMID: 32487596. DOI: 10.21873/anticanres.14283
    OpenUrlAbstract/FREE Full Text
  23. ↵
    1. Rowley KC,
    2. Gallion HH,
    3. Donaldson ES,
    4. van Nagell JR,
    5. Higgins RV,
    6. Powell DE,
    7. Kryscio RJ and
    8. Pavlik EJ
    : Prognostic factors in early vulvar cancer. Gynecol Oncol 31: 43-49, 1988. PMID: 3410354. DOI: 10.1016/0090-8258(88)90267-3
    OpenUrlCrossRefPubMed
PreviousNext
Back to top

In this issue

In Vivo: 35 (2)
In Vivo
Vol. 35, Issue 2
March-April 2021
  • Table of Contents
  • Table of Contents (PDF)
  • Index by author
  • Back Matter (PDF)
  • Ed Board (PDF)
  • Front Matter (PDF)
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word on In Vivo.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Perineural Invasion Correlates With Common Pathological Variables and Clinical Outcomes of Patients With Squamous Cell Carcinoma of the Vulva Treated With Primary Radical Surgery and Inguinal-femoral Lymphadenectomy
(Your Name) has sent you a message from In Vivo
(Your Name) thought you would like to see the In Vivo web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
10 + 2 =
Solve this simple math problem and enter the result. E.g. for 1+3, enter 4.
Citation Tools
Perineural Invasion Correlates With Common Pathological Variables and Clinical Outcomes of Patients With Squamous Cell Carcinoma of the Vulva Treated With Primary Radical Surgery and Inguinal-femoral Lymphadenectomy
ANGIOLO GADDUCCI, SABINA PISTOLESI, STEFANIA COSIO, CHIARA COMUNALE, ANTONIO FANUCCHI, ANTONIO GIUSEPPE NACCARATO
In Vivo Mar 2021, 35 (2) 1051-1056; DOI: 10.21873/invivo.12349

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Reprints and Permissions
Share
Perineural Invasion Correlates With Common Pathological Variables and Clinical Outcomes of Patients With Squamous Cell Carcinoma of the Vulva Treated With Primary Radical Surgery and Inguinal-femoral Lymphadenectomy
ANGIOLO GADDUCCI, SABINA PISTOLESI, STEFANIA COSIO, CHIARA COMUNALE, ANTONIO FANUCCHI, ANTONIO GIUSEPPE NACCARATO
In Vivo Mar 2021, 35 (2) 1051-1056; DOI: 10.21873/invivo.12349
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Patients and Methods
    • Results
    • Discussion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Cited By...

  • No citing articles found.
  • Google Scholar

More in this TOC Section

  • Evaluation of TET Family Gene Expression and 5-Hydroxymethylcytosine as Potential Epigenetic Markers in Non-small Cell Lung Cancer
  • Automated Non-coplanar Volumetric Modulated Arc Therapy Planning for Maxillary Sinus Carcinoma
  • The Influence of the Rapid Increase in the Number of Adverse Event Reports for COVID-19 Vaccine on the Disproportionality Analysis Using JADER
Show more Clinical Studies

Similar Articles

Keywords

  • Perineural invasion
  • vulvar squamous cell carcinoma
  • radical vulvectomy
  • inguinal-femoral-lymphadenectomy
  • recurrence
In Vivo

© 2023 In Vivo

Powered by HighWire