cow-2022-25

a) Differentiated vulvar intraepithelial neoplasia (dVIN)

b) Giant condyloma

c) Darier disease, hypertrophic / vegetating type

d) Squamous cell carcinoma, verrucous

e) Differentiated exophytic vulvar intraepithelial lesion(DEVIL)

f) Multiple Eccrine Syringofibroadenoma

1. c

Darier disease, hypertrophic / vegetating type

Previous biopsies from lesions elsewhere 27 years ago and along the years showed the same verruciform, pseudoepitheliomatouspattern, with no atypia. The diagnosis in those biopsies as well as in the resected specimen was Darier disease, hypertrophic / vegetating type. Extensive sampling showed no atypia and no invasive foci. All sampled areas showed the same pattern of parakeratosis, dyskeratosis (corps ronds and grains), suprabasal acantholysis and pseudoepitheliomatous hyperplasia with prominent anastomosing cords of elongated rete ridges (with a syringofibroadenoma silhouette). HPV hybridization situ was negative.

Darier disease is caused by impaired keratinocyte adhesion caused by inactivating mutations of SERCA2 –a type 2 sarcoendoplasmic reticulum CA2+-ATPase. Impaired imbalance of calcium intracellular homeostasis results in the characteristic apoptosis of keratinocytes. It is a rare disease that is usually transmitted in an autosomal dominant pattern. About 47% of patients do not show familial history and it has been explained by new mutations or incomplete penetrance. Disease presentation peaks at puberty, however, some patients may show signs of disease only by the sixth or seventh decades of life. Patients exhibit crusted and keratotic yellow-brown papules and plaques concentrated in “seborrheic” areas such as scalp ́, forehead, ears, nasolabial folds, upper chest, back and supraclavicular fossae. Lesions may be induced or exacerbated by stress, heat,or sweating; and are susceptible to bacterial, viral and fungal infections. Other characteristic forms of involvement are acrokeratosis verruciformis-like lesions in the back of the hands, white and red streaks in nails, and lesions in mucous membranes and genitalia.

Apoptotic fragments resultin typical features of dyskeratosis such as corps ronds (pyknotic nucleus surrounded by a clear halo and large keratohyalin bodies in granular layer) and grains (flattened cells with cigar-shaped nuclei in horny layer). A rare form of Darier disease is the hypertrophic / vegetating variant. It was described in 1949 by Beermanand included a case of mass forming lesion in male genitalia. Other case has been described of extensive involvement in anogenital area (Ji and colleagues 2018). Awareness of hypertrophic variant of Darier disease is of important to avoid the diagnosis of malignant transformation in long term disease –which is anexceedingly rare event.

1.Calonje JE, BrennT, Lazar A, Billings S. McKee’s Pathology of the Skin 5th Edition. 2018; Pages 190-195.

2.Beerman H. Hypertrophic Darier’s disease and nevus syringocystadenomatosus papilliferus; histopathologic study. Arch Derm Syphilol. 1949 Oct;60(4):500-27.

3. Aliağaoğlu C, Atasoy M, Anadolu R, Ismail Engin R. Comedonal, cornifying and hypertrophic Darier’s disease in the same patient: a Darier combination. J Dermatol. 2006 Jul;33(7):477-80.

4. Pezzini C, Vassallo C, Grasso V, Rivetti N, Borroni G. Pseudoepitheliomatous changes in a case of vegetating Darier–White disease: a unique histopathological finding. Am J Dermatopathol. 2015 Apr;37(4):323-5.

5. Ji WB, Joung SY, Min BW, Um JW. Surgical excision for non-familial hypertrophic Darier’s disease. ANZ J Surg. 2018 Jan;88(1-2):E77-E78.

Caroline Passos Cardoso
Federal University of Bahia / Hospital Universitário Professor Edgard Santos
Salvador, Bahia, Brazil

Daniel Athanazio
Imagepat, Laboratory of Pathology Federal University of Bahia / Hospital Universitário Professor Edgard Santos
Salvador, Bahia, Brazil

Vulva

Vulva; Darier Disease