Clinical History:
A 47 year old man presented to his dermatologist with a dark spot on his arm. Physical examination
showed a 0.9 x 0.7 cm brown flat lesion on his right arm. A shave biopsy was performed. Light
microscopy showed a nested and single cell population of melanocytes at the dermo-epidermal junction with
migration to the mid-spinous layers. These cells were epithelioid in character, had nuclei larger than
adjacent keratinocytes, manifested abundant quantities of irregularly-melanized pale cytoplasms, and
nuclei with prominent solitary nucleoli. There were no dermal stromal alterations one associates with
dysplastic nevi.
Case 1 - Figure A - Low magnification showing pagetoid and nested array of atypical epithelioid melanocytes. There is a peri-retal stromal fibrosing reaction with perivascular lymphocytes, melanophages and telangiectasia.
|
Case 1 - Figure B - Intermediate magnification shows the loosely cohesive, pagetoid and nested array of atypical melanocytic cells.
|
Case 1 - Figure C - High power shows atypical nuclei with slight indentation of contour, small, discrete nucleoli and open chromatin patterns. The degree of cytologic atypia is not one associated with criteria for fully transformed malignant degeneration.
|
Pathologic Diagnosis: De Novo Intraepidermal Epithelioid Melanocytic
Dysplasia
Introduction
Some atypical intraepidermal melanocytic proliferations defy classification as a junctional nevus and
have qualitative and quantitative abnormalities of epithelioid melanocyte proliferation that are
insufficient for a diagnosis of melanoma in situ. Similar lesions have been termed benign pagetoid
melanocytosis (Haupt and Stern, 1995; Stern and Haupt, 1998) and pagetoid Spitz nevus (Busam and
Barnhill, 1999). We use the term de novo intraepidermal epithelioid melanocytic
dysplasia for this distinctive morphological expression of pre-cancerous melanocytic proliferation
(Deng et al, 2002).
Clinical Features
De novo intraepidermal epithelioid melanocytic dysplasia represents a distinct pathologic entity that
cannot, on histologic grounds, be designated as a dysplastic nevus and lacks sufficient cytologic atypia
to warrant a diagnosis of melanoma in situ (Deng et al, 2002). We recently studied tissue sections from
such lesions in 39 patients (17 males and 22 females) aged 15-74 years. Lesions were flat with irregular
borders and variegate pigmentation located mainly on lower extremities(16) and trunk(13). The clinical
impression was typically that of melanoma, an "atypical mole" or dysplastic nevus, as the lesions had
irregular borders and a variegate pattern of pigmentation. Some lesions were uniform in color but had an
irregular border. The histories were reviewed for prior lesional skin biopsies or excisions : 9
patients had a history of melanoma elsewhere on the body, 10 had a high-grade dysplastic nevus, 4 had
other skin cancers, and 2 had banal nevi at other sites. Re-excisions of our cases showed 4 to have an
associated melanoma, 12 a severely dysplastic nevus, and 9 a residual banal nevus. Three patients had
denovo epithelioid dysplasia at more than 1 location. Only 4 patients had no associated lesions of
melanoma or dysplastic nevi in prior or present biopsies. Although the lesions may occur in a sporadic
fashion with a predilection for older patients, it has thus been our experience that they may also occur
in patients with familial dysplastic nevus syndrome or an antecedent history of melanoma.
Histopathology
Biopsies reveal a poorly circumscribed lesion characterized by gradual trailing-off of nevomelanocytes
at the lesional edge. The nevomelanocytes are distributed principally as single cells in a pagetoid
array, often forming small, abortive nests that are poorly formed with ill-defined margins that merge
with foci of single-cell pagetoid infiltration. Well-formed cleftlike spaces between the melanocytic
nests and the adjacent keratinocytes, as characterize the epithelioid Spitz nevus, are not observed. As
with the dysplastic nevus, any nests tend to by aberrantly disposed, being present at the sides of retia,
juxtaposed to the suprapapillary plates, or within the spinous layer of the epidermis. The stromal
alterations of dysplastic nevi, namely, concentric eosinophilic fibrosis or lamellar fibroplasia, the
associated inflammatory response and perivascular melanophages are usually absent.
Differential Diagnosis
In contrast to denovo melanocytic dysplasisa, the pagetoid Spitz nevus shows cleftlike spaces, a
predominance of nested over lentiginous melanocytes, numerous Kamino bodies, and a dominant populace of
monomorphous bland nevomelanocytes, including those in a pagetoid array. Mitoses may be seen within the
pagetoid Spitz nevus but are uniformly typical, whereas atypical mitoses may be seen in intraepidermal
melanocytic dysplasia. In melanoma in- situ, the pagetoid neoplastic cells have fully transformed
cytologic features of malignancy and a lentiginous proliferation that is confluent, typically with a
higher density of pagetoid spread and with effacement of the epidermal architecture. We hold epithelioid
melanocytic dysplasia to be a precursor to melanoma in situ that has many of the cytologic and
architectural features but in a fashion that is qualitatively and quantitatively insufficient to warrant
recognition as melanoma in situ.
Management
We advise complete lesional excision with a 5.0- to 10.0-mm margin of normal skin on all edges.
References
- Busam KJ, Barnhill RL. Pagetoid Spitz nevus. Intraepidermal Spitz tumor with prominent pagetoid
spread. Am J Surg Pathol 1995;19: 1061–1067.
- Deng A, Shendrik I, Magro CM, Crowson AN. De novointraepidermal
epithelioid melanocytic dysplasia: a distinctive lesion associated with malignant melanoma and severely
dysplastic nevi. Lab Invest 2002;82:98A
- Han MH, Koh KJ, Choi JH, Sung KJ, Moon KC, Koh JK. Pagetoid Spitz nevus: a variant of Spitz nevus.
Int J Dermatol 2000;39: 555-557
- Haupt HM, Stern JB. Pagetoid melanocytosis. Histologic features in benign and malignant lesions.
Am J Surg Pathol 1995;19: 792–797.
- Stern JB, Haupt HM. Pagetoid melanosis: tease or tocsin? Semin Diagn Pathol 1998;15:225-9.
