Pigmented squamous cell carcinoma of the scrotum associatedwith a lentigo

M.MATSUMOTO, H.SONOBE, T.TAKEUCHI, M.FURIHATA, J.IWATA, M.IKEDA*

AND Y.OHTSUKI

Department of Pathology, Kochi Medical School, Nankoku, Kochi 783-8505, Japan*Department of Dermatology, Kochi Prefectural Aki Hospital, Aki, Kochi, Japan

Accepted for publication 18 February 1999

Summary Only 13 cases of pigmented squamous cell carcinoma (SCC) have been reported in the Englishlanguage literature, with most frequent development in the oral cavity and conjunctiva. However, no

case of pigmented SCC of the scrotum has been reported. We report here a case of pigmented SCC that

arose primarily in the scrotum of a 70-year-old man. Light microscopically, this tumour exhibited thetypical features of a pigmented SCC, including not only keratinization and intercellular bridges but

also colonization by plump dendritic melanocytes with marked pigmentation. These features were

clearly con®rmed by immunohistochemistry, including strong positivity of tumour cells for high-molecular-weight cytokeratin and of colonizing melanocytes for HMB-45. The tumour was

associated with a lentiginous lesion and partly involved it. Melanocytes entrapped from the lentigo

might therefore have been activated during enlargement of this tumour, resulting in melanocytecolonization. Fourteen cases of pigmented SCC, including ours, are clinicopathologically reviewed.

Key words: lentigo, melanocyte colonization, pigmented squamous cell carcinoma, scrotum

Pigmented squamous cell carcinoma (SCC) is a rare

variant of SCC which contains numerous pigmentedmelanocytes. This type of SCC may be dif®cult to

distinguish from cutaneous melanoma. To our knowl-

edge, only 13 cases of pigmented SCC have beenreported in the English language literature, with most

frequent development in the oral cavity or con-

junctiva.1±11 However, no case of scrotal pigmentedSCC has been reported. We report here a case of scrotal

pigmented SCC accompanied by lentigo, and review the

clinicopathological characteristics of the 14 reportedcases of pigmented SCC including the present one.

Case report

A 70-year-old man, who was a of®ce worker, with no

history of occupational exposure to mineral oils or tars,

presented with a longer than 1-year history of a smallulcerative lesion of the scrotum which had gradually

increased in size and become black in colour. On

macroscopic inspection, the scrotal lesion measured

12 ´ 8 mm, exhibited ulceration (Fig. 1, arrow), and

was suspected to be a malignant melanoma. It wasremoved with a 5-mm margin. No evidence of recur-

rence or metastasis has been found for 5 months after

removal.The surgically resected specimens were ®xed in 10%

phosphate-buffered formalin solution and embedded in

paraf®n in a routine manner. Dewaxed sections werestained with haematoxylin and eosin, Berlin-blue, and

Fontana±Masson. Additional sections were examined

with antibodies against low-molecular-weight cytokeratin(35bH11, 1 : 5000, Enzo Diagnostic, New York, NY,

U.S.A.), high-molecular-weight cytokeratin (34bH12,

1 : 2000, Enzo Diagnostic), melanoma (HMB-45, 1 : 8000,Enzo Diagnostic), S-100 protein (1 : 400, Dakopatts,

Glostrup, Denmark) and vimentin (V9, 1 : 50, Dakopatts).

For antigen retrieval, the sections for cytokeratin studieswere pretreated with pronase for 10 min at 37 8C, and

those for HMB-45, S-100 and vimentin studies were

heated at 95 6 5 8C in 10 mmol/L citrate buffer in amicrowave oven for 5 min. Immunohistochemical stain-

ing for these proteins was performed using the streptavidin±

biotin complex procedure (Dako Labs Kit, AP: Dako,Carpinteria, CA, U.S.A.) according to the kit manual.

British Journal of Dermatology 1999; 141: 132±136.

132 q 1999 British Association of Dermatologists

Correspondence: Hiroshi Sonobe. E-mail: sonobeh@kochi-ms.ac.jp

Using light microscopy, the black ulcerated lesion wascomposed of atypical short spindled or polygonal epithe-

lial cells, compactly proliferating in a sheet-like pattern

with in®ltration into the dermis (Fig. 2a). A lentiginouslesion was found adjacent to this tumour (Fig. 2b)

which partly involved the lentigo. These tumour cells

harboured large, hyperchromatic, irregularly shapednuclei and large prominent nucleoli. In parts of the

tumour, intracellular bridges among tumour cells and

occasional individual keratinized cells were found(Fig. 2c). Mitotic ®gures, including pathological ones,

were frequently observed. Several plump dendritic cells

with atypical nuclei containing prominent nucleoli andnumerous intracytoplasmic pigmented granules were

intermingled with other cells throughout the lesion, but

were most frequently detected in its peripheral portions(Fig. 2d). These granules were positive for Fontana±

Masson staining for melanin (Fig. 2e) but not for Berlin-blue staining for iron. Melanophages were also scattered,

mostly in the stroma.

The tumour cells were strongly positive for high-molecular-weight cytokeratin (Fig. 2f), but were not

positive for low-molecular-weight cytokeratin, while the

intermingled plump dendritic melanocytes were positive

for HMB-45 (Fig. 2g), S-100 protein (Fig. 2h) and vimen-tin. However, melanocytes in the lentigo adjacent to this

tumour were negative for HMB-45, S-100 protein and

vimentin. Based on these ®ndings, we diagnosed thistumour as a pigmented SCC of the scrotum.

Discussion

The scrotal tumour presented here was a typical pig-

mented SCC, as con®rmed by the results of specialstaining and immunohistochemical examination. To

date, 14 cases of pigmented SCC, including the present

one, have been reported, as shown in Table 1. Of 14cases, the age, sex and site were described in all cases,

but race, size, treatment and outcome were mentioned

in 13, 12, 10 and six cases, respectively. The mean ageof patients was 59 years, with a range of 47±81 years.

Eleven were men and three women. Eight of the 13

cases arose in black people, three in Japanese, and twoin white people, although the reason why the frequency

of pigmented SCC is different among races is unclear.

Seven tumours developed in the oral cavity, four in theconjunctiva, one in the pinna of the right ear, one in

the nasal cavity and one in the scrotum. Most of the

tumours were small, with a mean diameter of 15 mmand a range of 5±30 mm. Simple extirpation was

performed in six of 10 cases, simple extirpation andenucleation of eyeball for recurrence in one, excision

and lymph node dissection in one, and enucleation of

eyeball with radiation therapy and wide excision withregional lymph node dissection in the remaining two.

The outcome in six cases was fairly good, and all

patients were alive without recurrence or metastasisfrom 5 months to 9´5 years after surgery. With early

diagnosis and treatment or no clinical ®ndings of lymph

node metastasis, most patients with ordinary non-pigmented SCC of the skin, conjunctiva or oral cavity

have a favourable prognosis.12±14 In addition, for

pigmented SCC of the nasal cavity, no signi®cantrelationship between the degree of pigmentation and

the degree of malignancy was found.11 Pigmented SCCs

thus appear to exhibit nearly the same biologicalbehaviour as non-pigmented SCCs, and both have a

good prognosis.

Melanocyte colonization or marked pigmentation hasbeen reported in various types of tumour, including

basal cell carcinoma,15 Paget's disease,16 seborrhoeic

keratosis,17 breast adenocarcinoma18 and ovarian der-moid.19 The mechanism of melanocyte colonization

remains controversial. Melanocyte colonization occurs

in breast cancer only when cancer cells reach the

PIGMENTED SQUAMOUS CELL CARCINOMA 133

q 1999 British Association of Dermatologists, British Journal of Dermatology, 141, 132±136

Figure 1. Gross appearance of the present case of pigmented scrotal

squamous cell carcinoma, revealing a black ulcerative lesion (arrow).

134 M.MATSUMOTO et al.

q 1999 British Association of Dermatologists, British Journal of Dermatology, 141, 132±136

Figure 2. Light microscopic appearance of the scrotal pigmented squamous cell carcinoma (SCC). (a) The central portion of this lesion was composedof atypical tumour cells, compactly proliferating in a sheet-like pattern in®ltrating into the dermis (haematoxylin and eosin (H&E), original

magni®cation ´ 100). (b) Lentigo (L, arrowheads) was found adjacent to the pigmented SCC (T) (H&E, original magni®cation ´ 100). (c) Occasional

keratinization and intercellular bridges are observed in parts of the tumour (H&E, original magni®cation ´ 200). (d) Several plump dendriticmelanocytes with brown pigmented granules are intermingled in this lesion (H&E, original magni®cation ´ 250); (e) these granules were strongly

positive for Fontana±Masson staining for melanin (Fontana±Masson, original magni®cation ´ 200). (f±h) Most tumour cells are strongly positive for

high-molecular-weight cytokeratin (f), and melanocytes intermingled in this tumour are positive for HMB-45 (g) and S-100 protein (h)

(streptavidin±biotin complex method, original magni®cation ´ 200).

epidermal±dermal interface; physical contact of these

cells with the basal layer was shown to play an impor-

tant part in the melanocyte colonization.18 It has beensuggested that in corneal and conjunctival pigmented

SCCs, cancer cells produce unknown factors that pro-

mote melanocytic colonization and melanin produc-tion.2 As for the melanocyte colonization in the

present case, several plump dendritic melanocytes inter-

mingled among the tumour cells were positive for HMB-45, S-100 and vimentin, and these cells, although

atypical, were considered non-neoplastic, as a positivereaction for HMB-45, speci®c for melanoma cells, is also

exhibited in stimulated melanocytes.20 In addition, a

lentiginous lesion, which included many melanocytes,was associated with the tumour and involved by it,

although it is unclear whether the SCC occurred in the

lentigo or the two lesions coincided with each other.Melanocytes entrapped in the lentigo might thus have

been activated during tumour enlargement, resulting in

melanocyte colonization. No other case of pigmentedSCC associated with lentigo has been reported.

In conclusion, this is the ®rst case report of pigmented

SCC of the scrotum. This tumour involved a lentiginouslesion adjacent to it, and entrapped melanocytes of the

lentigo might therefore have been activated along with

tumour enlargement. Further studies of additional caseswill be needed to clarify the mechanism of melanocyte

colonization in pigmented SCC.

Acknowledgments

The authors thank Prof. Toshiaki Manabe (Departmentof Pathology, Kawasaki Medical School, Kurashiki,

Okayama, Japan) for his invaluable advice in this case,

and also Mr Takuya Yamaguchi (Department of Pathol-ogy, Kochi Medical School, Nankoku, Kochi, Japan) for

his technical assistance.

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Table 1. Clinical summary of pigmented squamous cell carcinomas in the literature

First author,

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