Case Conference January 4th 2017

04-Jan-2017, Divisi Ginekologi Onkologi RSCM

CASE CONFERENCE

January 4^th, 2017

Mrs Y

 

Case Description:

 

Patient was referred from dermatologist with extramammary Paget disease on the vulva. Patient has complained of itchy and reddish area on the vulva since around a year ago. She had been treated with anti fungal agents and allergic agents but there was no improvement even the area was getting wider. Patient was biopsied on October 26^th 2016 and PA results showed histologic pattern of extramammary Paget disease.

Physical examination on November 16^th, 2016:

General status:

CM. BP: 140/80mmHg, HR: 75 bpm, RR: 20x/m, T:36^oC, Height 160cms, Weight 71kgs

Head: Pale conjungtiva (-/-)

Neck: supraclavicula lymph nodes (-/-)

Axilla: lymph nodes (-/-)

Thorax: mammae lump (-/-) mass (-/-),  symmetry shape and movement of hemithorax

Lung: vesicular breath sound on both lungs, no wheezing or rhales

Cardia: no murmur, no gallop

Abd: flat, no palpable mass

 

Extremity: inguinal lymph nodes (-/-)

 PA results, Oct 26^th, 2016

Macro:

2 Specimens were received.

1.       1^st specimen from right labia majora: 1 piece tissue with skin size 1x0.3x0.1 cm, dark brown, soft, all mounted

2.       2^nd specimen from left labia majora: 1 piece tissue with skin size 0.7x0.3x0.1 cm, light brown, soft, all mounted

Micro:

1.       Tissues were completed with skin layered by epidermis with orthokeratosis, hyperkeratosis, acanthosis, and spongiosis. Some epidermis showed atypical cell with pleomorfic nuclei, rough chromatin, obvious nucleolus, and clear large cytoplasm. Some superficial dermis showed inflammatory cells such as interstitial lymphocytes.

2.       Tissues  were completed with skin layered by hyperkeratosis and ulcerative epidermis. On epidermis, there was epithelial tumor. Tumor cells’ nuclei were round/oval, vesicular, some of them with more than one nucleus, eosinophilic cytoplasm. Among them there were some abcesses and polymorphonuclear inflammatory cells. Mytosis were found also. On fibrotic dermis, there were limphocytes, plasma cells, polymorphonuclear cells, and lots of vessels with various sizes, congestive.

 Conclusion: Extramammary Paget disease.

Discussion

Since Paget disease is a very rare disease, there are no guidelines which state the systematic work up and treatment. There are three theories which develop the origins of EMPD.

1.       It is suggested to arise from adnexal structures, like aocrine glands, multipotent stem cells in the epidermal basal layer, or infundibular stem cells of the hair follicles.

2.       It is also suggested from mammary-like glands which are located in the interlabial sulci. It is theorized to come from Toker cells, single round nucleus and pale cytoplasm cells usually reside in the nipple and aerola.

 Work up for vulvar Paget disease includes history taking of vulvovaginal complaints, gastrointestinal, and urology symptoms since the malignancy arising from apocrine-gland-bearing skin cells or as manifestation of adjacent primary anal, rectal or bladder adenocarcinoma. Patient has been evaluated for her full gynecological examination including rectal examination. Biopsy has been done unfortunately the depth of the invasion was not stated.

There is a vast range of interventions from surgical to non-invasive techniques. The challenges rely on how to remove the disease that may not be visible clinically.

A thorough systematic search has been done to come with a scientifically well defined treatment in 2013 by Edey KA et. al. (Cochrane’s review). There are no reliable evidence to inform decisions about different interventions for women with Paget disease of the vulva. Surgery is still the main intervention although there are still no a multicentre RCT available. Surgery of EMPD consists mainly of wide local excision with or without inguinofemoral lymph node dissection.  Surgical margin and the defect after excision are the clinical challenges. Paget cells are difficult to recognize during frozen section. False negative are ranging from 10-13%. However the relationship between free margin surgery and recurrence remains unclear. Local recurrence rates after surgical treatment of vaginal EMPD are vast from 34-56%, even after reconstructive skin grafts and flaps. Studies also showed high recurrence rates regardless of the status of free margin.  

Other modality of treatment is radiotherapy. It has been used as primary option for patients who were not eligible for operation or refused operation. As previous treatment discussed, radiotherapy isn’t reported as clinical trial either. Radiotherapy alone is an alternative therapeutic approach for patients with extensive inoperable disease or medical contraindications. Definitive radiotherapy can be used in elderly patients and/or with medical contraindications. Adjuvant radiotherapy may be considered in presence of risk factors associated with local recurrence as dermal invasion, lymph node metastasis, close or positive surgical margins, perineal, large tumor diameter, multifocal lesions, extensive disease, coexisting histology of adenocarcinoma or vulvar carcinoma, high Ki-67 expression, adnexal involvement and probably in overexpression of HER-2/neu. Salvage radiotherapy can be given in inoperable loco-regional recurrence and to those who refused additional surgery.Long term follow-up shows that recurrence rates after radiotherapy are less than 20%. Adjuvant postoperative radio-therapy was given to 51 patients (55.4%), and 40 patients receivedradiotherapy as primary treatment. A dose of 40–50 Gy is recommended for intraepithelial is recommended for intraepithelial EMPD and 55–65 Gy is recommended for invasive EMPD or for an associated adenocarcinoma.

 

Conclusion

In this patient, the best choice of treatment is wide local excision with the final goal is to have free margin status. 

 

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