ARTICLE
Porokeratosis is a genetically determined skin disorder characterized
by circular lesions with distinct peripheral ridges that histopathologically
correspond to a parakeratotic column. Among the different types of porokeratosis,
linear porokeratosis is rare and distinct because of the characteristic
linear distribution of the lesions and increased susceptibility to malignant
transformation [1]. Here, we report a case of linear porokeratosis that
developed multiple squamous cell carcinomas.
Case report
A 61-year-old Japanese woman had first noticed in her early teens brown
eruptions on the left side of the trunk. They increased in number gradually
and developed on torso and extremities, mainly on the left side. One year
prior to her first visit, an ulcerating tumor developed on the left elbow,
which became larger and painful.
On physical examination, an ulcerating tumor measuring 5 cm in diameter
was seen in the left cubital fossa (Fig.
1). The ulcer was covered with necrotic or keratotic material,
and the margin was elevated. Physical examination also exhibited many
round dark brown macules with peripheral keratotic ridges up to 1 to 2
cm in diameter. Most of these were distributed on the left side of the
body, while a small number of similar but smaller and lighter-colored
lesions were noted, scattered on the right side of the body (Fig.
2).
The lesions on the left side of the body were arranged in a linear pattern
running from the dorsal aspect to the ventral aspect obliquely on her
shoulder, lateral chest wall, abdominal wall. On the center of the lower
abdomen, they were arranged in a vertical longitudinal line. On the left
extremities, a linear to oblique pattern was noted. This pattern of distribution
of the lesions was consistent with Blaschko's lines. The ulcerating tumor
was located within a streak of porokeratotic lesions on the left cubitus.
Under general anesthesia, the tumor of the left
cubitus was resected and the skin defect was covered with a skin graft.
Histopathologically the tumor was diagnosed as a well-differentiated squamous
cell carcinoma with invasive growth of atypical keratinocytes into the
whole dermis and upper part of subcutaneous tissue (Fig.
3). The hyperpigmented annular lesions showed typical histopathologic
features of porokeratosis, namely an invagination of the epidermis containing
a cornoid lamella (Fig. 4).
Immuno-histochemical studies disclosed an increased p53 expression within
the tumor cells, but not within the keratinocytes underlying the cornoid
lamella.
She was noted to have 4 additional lesions of early but invasive squamous
cell carcinomas on her left buttock, left thigh, left waist and left hip.
All of them were located within the linear areas of pronounced porokeratotic
lesions. These tumors were resected. Ten years later, she came back to
us because of ulcerating tumors on her left shoulder, left elbow and left
thigh. These tumors were resected and diagnosed histopathologically as
moderately to well differentiated squamous cell carcinomas. No metastasis
to lymphnodes or distant organs has been noted so far.
She had had tuberculosis at the age of 16 and had undergone left mammectomy
because of breast cancer when she was 44 years old. Her elder brother,
72 years old, had widely distributed disseminated superficial porokeratosis
(Fig. 5) and liver cirrhosis.
He had been an out-door worker and extensive exposure to sunlight was
supposed. His daughter, 38 years old, had a small number of scattered
porokeratotic lesions. These family members were shown both clinically
and histopathologically to have disseminated superficial porokeratosis.
Skin tumors or any linear distribution of porokeratotic lesions were not
seen. They claimed that some of their family members had similar cutaneous
lesions (Fig. 6).
Discussion
The segmental distribution of the skin lesions in this case can be best
explained by an early postzygotic mutation in addition to a mutation of
the other allele, the latter being also present in several other family
members. There are several pieces of evidence that support this concept
of pathogenesis. First, her family tree shows that the mode of inheritance
is autosomal dominant. Second, several other family members had disseminated
superficial porokeratosis but not linear porokeratosis. Third, the right
side of the patient's body showed mild involvement in the form of disseminated
superficial porokeratosis, namely, sparsely distributed, small and light-colored
non-linear lesions. Fourth, the segmental involvement on the left side
of the body was distributed along Blaschko's lines, and showed a far more
pronounced degree of severity in color and size than on the right side
of the body. Thus, this case could be best explained by an early postzygotic
mutational event giving rise to loss of heterozygosity at the locus responsible
for the porokeratotic trait and resulting in a type 2 segmental manifestation
of disseminated superficial porokeratosis showing a systematized pattern
of involvement [2-4].
Furthermore, the present case showed the development of 9 squamous cell
carcinomas. All of these tumors arose within the segmental lesions on
the left side of the body and not on the right side of the body where
only smaller and lighter-colored lesions were sparsely distributed. It
is known that skin cancers may develop on the lesions of porokeratosis,
particularly in the linear type [5]. This case may be a good example of
the high proneness to malignant degeneration of linear porokeratosis.
Happle suggested that prenatal loss of heterozygosity may represent an
initial step in the development of cancer on linear porokeratosis [4].
Nelson et al. [6] demonstrated immunohistochemically
an increased p53 expression within keratinocytes underlying the cornoid
lamella, suggesting the role of p53 in the pathogenesis of the porokeratoses.
In the present case, immunohistochemical studies demonstrated an increased
p53 expression within the atypical keratinocytes constituting the carcinomatous
lesions, but no over-expression of p53 was demonstrated within keratinocytes
underlying the cornoid lamella. Anzai et al. studied a similar
case of squamous cell carinoma and linear porokeratosis, and they reported
that p53 over-expression was observed in the tumor cells, but not in the
porokeratotic lesions [7]. Recently, Xia et al. identified a locus
at chromosome 12q23.2-24.1. responsible for disseminated superficial actinic
porokeratosis [8]. The gene coding p53 maps on 17p13.1 [9] distinct from
that mentioned by Xia et al.
Further investigation is needed to elucidate the pathogenesis of linear
porokeratosis and the mechanism of development of malignant lesions from
porokeratosis..
Article accepted on 5/3/01
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