Letters to the Editor
To the Editors:
Recently, we observed the first known case of placental alkaline phosphatase (PLAP) immunoreactivity in metastatic melanoma. PLAP is a 70-kDa protein that is normally produced by primordial germ cells and syncytotrophoblasts. PLAP expression is valuable in the diagnosis of various germ-cell (eg, seminoma and intratubular germ cell neoplasia) and non–germ-cell tumors, including pulmonary, ovarian, gastrointestinal, and uterine carcinomas. PLAP reactivity has also been reported in uteri of mice, normal muscle tissue, soft tissue tumors with myogenic differentiation, and uterine leiomyoma. PLAP functionality remains unclear, but some investigators suggest it regulates the migration of fetal primordial germ cells.1–4 To this date, PLAP immunoreactivity has yet to be documented in metastatic melanoma.
We report a 61-year-old woman from Venezuela who was referred to our institution. She had presented initially in 1979 at another hospital with a small subungual lesion on the right fifth digit. The lesion was resected, but the slides were unavailable for review. She was asymptomatic for 32 years, when she noticed several nodules in her right axilla and submental region. Needle core biopsy of the axillary mass, reviewed at the referring institution, revealed lymph node reactive hyperplasia without evidence of malignancy. Fine needle aspiration and flow cytometry of the submental mass and adjacent lymph node, reviewed at our institution, demonstrated a clonal diffuse infiltrate of small B cells, negative for CD23, CD5, cyclin D1, and CD10, and thus consistent with a low-grade B-cell lymphoma. Several months later, she noticed “golf ball–sized” enlargement of the right axillary mass. Excisional biopsy, reviewed at our institution, revealed a malignant epithelioid process in one lymph node (Fig. 1A). Because of lack of an obvious primary malignancy, we used a panel of immunohistochemical studies. Immunohistochemistry demonstrated tumor cell positivity with a melanocytic cocktail and anti-PLAP antibody with a cytoplasmic pattern while being negative for keratin (Figs. 1B, C). Based on the labeling with the melanocytic cocktail and the history of subungual melanoma, we established a diagnosis of metastatic melanoma. The patient underwent completion lymphadenectomy with a total of 2 of 15 axillary lymph nodes positive for melanoma, with a largest tumor deposit of 63 mm. During a follow-up of 10 months, the patient has developed multiple metastases to the lungs, liver, and spleen. She was started with high-dose interferon with minimal response. She recently started with a protocol of ipilimumab and temozolomide.
It has been previously proposed that cytoplasmic reactivity of PLAP may represent nonspecific binding of the antibody, particularly because of its reported subcellular localization in the cytoplasmic membrane. However, because both cytoplasmic and membranous labeling is observed in placenta and seminoma, the cytoplasmic expression is more likely to be a result of abnormal subcellular localization of the protein.1
The only previous mention of alkaline phosphatase in metastatic melanoma was in a histochemical study by Kabat and Furth.5 They investigated the presence of alkaline phosphatase in both normal and malignant tissues, of which 2 samples were malignant melanoma. Both of these samples failed to demonstrate alkaline phosphatase histochemical reaction.5
In conclusion, to our knowledge, we report the first case of PLAP positivity in metastatic melanoma. Histopathologists should be aware of this possibility, as PLAP may be used in immunohistochemical panels in diagnostic surgical pathology and dermatopathology and thus may be a possible source of misdiagnosis.
1. Goldsmith JG, Pawel B, Goldblum JR, et al.. Detection and diagnostic utilization of placental alkaline phosphatase in muscular tissue and tumors with myogenic differentiation. Am J Surg Pathol. 2002;26:1627–1633.
2. Jeppsson A, Wahren B, Brehmer-Andersson E, et al.. Eutopic expression of placental-like alkaline phosphatase in testicular tumors. Int J Cancer. 1984;34:757–761.
3. Lange PH, Millan JL, Stigbrand T, et al.. Placental alkaline phosphatase as a tumor marker for seminoma. Cancer Res. 1982;42:3244–3247.
4. Loose JH, Damjanov I, Harris H. Identity of the neoplastic alkaline phosphatase as revealed with monoclonal antibodies to the placental form of the enzyme. Am J Clin Pathol. 1984;82:173–177.
5. Kabat EA, Furth J. A histochemical study of the distribution of alkaline phosphatase in various normal and neoplastic tissues. Am J Pathol. 1941;17:303–318.