1 Medical Oncology Unit, Head and Neck Department; 2 Pathology Unit B; 3 Radiology Department; 4 Head and Neck Surgery Department; Istituto Nazionale Tumori, Milan, Italy
*E-mail: lisa.licitra@istitutotumori.mi.it
Salivary gland carcinomas (SGCs) account for 15% of all head and neck cancers and include different histotypes. Salivary gland adenocarcinomas (SGA) represent 16% of parotid gland cancers [1].
Chemotherapy is delivered only with a palliative aim in metastatic and/or recurrent disease. The response rate ranges from 10% to 30% and complete remissions are anecdotal [2].
Immunoreactivity for androgen receptor (AR) has been reported in SGCs, suggesting that an approach with anti-androgen drugs could be envisaged [3].
To date a single case of parotid adenocarcinoma achieving a partial remission after treatment with a luteinizing hormone-releasing hormone (LHRH) analogue has been described [4].
Herein we report a case with AR-positive relapsed parotid adenocarcinoma achieving a complete remission with androgen-deprivation therapy.
A 73-year-old man, referred to a right parotidectomy and postoperative radiotherapy for an adenocarcinoma of the parotid gland, presented at our observation with a right preauricolar ulcerated lesion (Figure 1A). A biopsy confirmed a local recurrence. AR immunostaining in 100% of the neoplastic cells nuclei was demonstrated (diluted 1:50; Biogenex, CA, USA). The streptavidinperoxidase technique was used and antigen retrieval was employed.
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The patient received a complete anti-androgen blockade (CAB) with monthly triptorelin (LHRH analogue) and bicalutamide. Skin lesions reduced rapidly, until disappearance 2 months later (Figure 1B). A CT scan confirmed a complete remission.
Unfortunately, the patient developed a Philadelphia-negative chronic myelocytic leukemia (CML). In addition to undergoing CAB, he received chemotherapy for CML. He soon died of progressive CML, still in complete clinical remission.
To the best of our knowledge, this is the first case of SGA obtaining a complete remission by a hormone therapy. The regression of the local recurrence suggests an underlying hormone-dependent disease behavior. Unfortunately, we were not able to determine response duration. Nevertheless its occurrence and quickness, as well as the excellent tolerability (in terms of toxicity and costs) of the anti-androgen treatment represents a very valuable result, bearing in mind the poor results in recurrent and/or metastatic SGCs obtained with chemotherapy.
Normal salivary gland tissue has been recognized to positively stain for PSA, independently of gender, while immunostaining for AR has not been consistently found [6, 7]. Immunostaining for AR, and occasionally for prostatic acid phosphatase and PSA, has been reported in duct carcinoma and adenocarcinoma of salivary glands in both sexes [36, 8]. These findings suggest that, unlike prostate cancer, PSA expression could be independent of androgen stimulation in normal salivary gland tissue. However, the biological significance of PSA and AR expression in normal tissue and in SGCs, respectively, remains unknown.
In prostatic cancer, androgens play a role as both a survival and growth factor and androgen-deprivation therapy is successfully used.
Our experience suggests that a similar mechanism may be implicated in AR-positive salivary gland tumors. Studies looking at the underlying biological role of AR expression in SGCs are warranted.
This work was supported in part by AIRC (Associazione Italiana per la Ricerca sul Cancro).
L. D. Locati1, P. Quattrone2, P. Bossi1, A. V. Marchianò3, G. Cantù4 & L. Licitra1*
1Medical Oncology Unit, Head and Neck Department; 2Pathology Unit B; 3Radiology Department; 4Head and Neck Surgery Department; Istituto Nazionale Tumori, Milan, Italy (*E-mail: lisa.licitra@istitutotumori.mi.it)
References
1. Sessions RB, Harrison LB, Forastiere AA. Tumors of the salivary glands and paragangliomas. In De Vita V Jr, Hellman S, Rosenberg SA (eds): Cancer: Principles and Practice of Oncology, 6th edition. Philadelphia, PA: Lippincott Williams and Wilkins 2001; 886906.
2. Licitra L, Grandi C, Prott FJ et al. Major and minor salivary glands tumours. Crit Rev Oncol Hematol 2003; 45: 215225.[ISI][Medline]
3. Fan CY, Wang J, Barnes EL. Expression of androgen receptor and prostatic specific markers in salivary duct carcinoma. An immunohistochemical analysis of 13 cases and review of the literature. Am J Surg Pathol 2000; 24: 579586.[CrossRef][ISI][Medline]
4. van der Hulst RWM, van Krieken JHJM, van der Kwast TH et al. Partial remission of parotid gland carcinoma after goserelin. Lancet 1994; 344: 817.
5. Fan CY, Melhem MF, Hosal AS et al. Expression of androgen receptor, epidermal growth factor receptor and transforming growth factor alpha in salivary duct carcinoma. Arch Otolaryngol Head Neck Surg 2001; 127: 10751079.
6. Tazawa K, Kurihara Y, Kamoshida S et al. Localization of prostate-specific antigen-like immunoreactivity in human salivary gland and salivary gland tumors. Pathol Int 1999; 49: 500505.[CrossRef][ISI][Medline]
7. Laine M, Blauer M, Ylikomi T et al. Immunohistochemical demonstration of androgen receptors in human salivary glands. Arch Oral Biol 1993; 38: 299302.[CrossRef][ISI][Medline]
8. Moriki T, Ueta S, Takahashi T et al. Salivary duct carcinoma: cytologic characteristics and application of androgen receptor immunostaining for diagnosis. Cancer Cytopathol 2001; 93: 344350.[ISI]