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Pigmented esthesioneuroblastoma showing dual differentiation following transplantation in nude mice

An immunohistochemical, electron microscopical, and cytogenetic analysis

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Summary

Esthesioneuroblastoma (ESTH) is a neuroepithelial-cell-derived neoplasm of the olfactory mucosa composed of homogeneous small round cells which contain neurosecretory granules. Melanin has been detected in such tumours only occasionally. Here we describe a new case of ESTH with divergent differentiation. The primary neoplasm was found in a 67 year-old female, involving the left nasal and maxillary sinus; she died of cerebral metastasis ten months after diagnosis. Histologically only small round cells were seen, with S-100 and NSE positivity. Electron microscopy revealed neurosecretory granules and filaments, as well as the occasional presence of melanosomes. A nude mice xenograft line has been established, and is presently in its ninth transfer. Two cell types are present: small round-to-spindle shaped cells with neural features, and large epithelial-like ones. Both immunohistochemistry and electron microscopy confirm this dual differentiation, with the presence of membrane-bound dense-core neural secretion, as well as melanosomes of neuroectodermal origin. Additionally, an in vitro cell line has been established. Cytogenetic analysis confirmed the presence of both malignant human melanoma patterns; non-random abnormalities in chromosomes 1 and 6, extra copies of chromosome 7. Duplication of the long arm of chromosome 14, as seen in olfactory neuroblastoma, is also seen.

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References

  • Axe S, Kuhajda FP (1987) Esthesioneuroblastoma. Intermediate filaments, neuroendocrine and tissue-specific antigens. Am J Clin Pathol 88:139–145

    Google Scholar 

  • Balaban GB, Herlyn M, Clark WH Jr, Nowell C (1986) Karyotypic evolution of human malignant melanoma. Cancer Genet Cytogenet 19:113–122

    Google Scholar 

  • Berger L, Luc G, Richard D (1924) L'esthesioneuroepitheliome olfatif. Bull Assoc Franc Etude Cancer 13:410–421

    Google Scholar 

  • Burns J (1982) The unlabelled antibody peroxidase-antiperoxidase method: In: Bullock GR, Petrusz P (eds) Techniques in Immunohistochemistry. Academic Press, London, pp 91–105

    Google Scholar 

  • Cavazzana AO, Navarro S, Noguera R, Reynolds PC, Triche T (1988) Olfactory neuroblastoma is not a neuroblastoma but is related to primitive neuroectodermal tumor (PNET) In:Evans AE, D'Angio GJ, Knudson AG, Seeger RC (eds) Advances in neuroblastoma research 2. Prog Clin Biol Res, vol. 271. Alan R. Liss, Inc., New York, pp 463–474

    Google Scholar 

  • Cebelin MS (1980) Melanocytic bronchial carcinoid tumors. Cancer 46:1843–1848

    Google Scholar 

  • Chadarevian JP, Montes MJ, O'Gorman AM, Freeman AR (1987) Maturation of cerebellar neuroblastoma into ganglioneuroma with melanosis. A histologic, immunocytochemical and ultrastructural study. Cancer 59:69–76

    Google Scholar 

  • Chaudhry AP, Haar JG, Koul A, Nickerson PA (1979) Olfatory neuroblastoma (esthesioneuroblastoma). A light and ultrastructural study of two cases. Cancer 44:564–579

    Google Scholar 

  • Choi HSH, Anderson PS (1985) Immunohistochemical diagnosis of olfactory neuroblastoma. J Neuropathol Exp Neurol 44:18–31

    Google Scholar 

  • Curtis JL, Rubinstein LJ (1982) Pigmented olfatory neuroblastoma. A new example of melanotic neuroepithelial neoplasm. Cancer 49:2136–2143

    Google Scholar 

  • Dehner LP, Sibley RR, Sauk JJ, Vickers RA, Nesbit ME, Leonard AS, Waite DE, Neeley JE, Ophoven J (1979) Malignant melanotic neuroectodermal tumor of infancy: A clinical, pathological, ultrastructural and tissue-culture study. Cancer 43:1389–1420

    Google Scholar 

  • Dhillon AP, Rode J, Leathem A (1982) Neuron specific enolase: an aid to the diagnosis of melanoma and neuroblastoma. Histopathology 6:81–92

    Google Scholar 

  • Erlandson RA (1985) Melanotic Schwannoma of spinal nerve origin. Ultrastr Pathol 9:123–129

    Google Scholar 

  • Fogh J, Tiso J, Sharkey E, Fogh JM, Daniels W (1980) Twenty-three new human tumor lines established in nude mice. Exp Cell Biol 48:229–239

    Google Scholar 

  • Gatter KC, Pulford KAF, Vanstapel MJ, Roach B, Mortimer P, Woolston RE, Taylor J, Lane EB, Mason DY (1984) An immunohistochemical study of benign and malignant skin tumors: epithelial aspects. Histopathology 8:209–227

    Google Scholar 

  • Gown AM, Vogel AM, Hoak D, Gough F, McNutt MA (1986) Monoclonal antibodies specific for melanocytic tumors distinguish subpopulation of melanocytes. Am J Pathol 123:195–203

    Google Scholar 

  • Hadju SJ, Lemos LB, Kozakewich H, Helson L, Beattie E (1981) Growth pattern and differentiation in human softtissue sarcomas in nude mice. Cancer 47:90–98

    Google Scholar 

  • Hahn JF, Netsky MG, Butter AB, Sperber DD (1976) Pigmented ganglioneuroblastoma: relation of melanin and lipofuscin to Schwannomas and other tumors of neural crest origin. J Neuropathol Exp Neurol 35:393–403

    Google Scholar 

  • Hata J, Ueyama Y, Tamaoki N (1984) Transplantability and differentiating capacity of human tumors of neuroblastic, nephroblastic and germ cell origin in nude mice. In: Sordat B (ed) Immunedeficient animals. S Karger AG, Basel, pp 291–297

    Google Scholar 

  • Homzie MJ, Elkon D (1980) Olfatory esthesioneuroblastoma. Variables predictive of tumor control and recurrence. Cancer 46:2509–2513

    Google Scholar 

  • Hsu A-M, Raine L, Fange H (1981) Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase technique; a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 29:557–580

    Google Scholar 

  • ISCN (1985) An international system for human cytogenetic nomenclature. S Karger AG, Basel

    Google Scholar 

  • Johnson RE, Scheithauer BW, Dahlin DC (1983) Melanotic neuroectodermal tumor of infancy. A review of seven cases. Cancer 52:661–666

    Google Scholar 

  • Kadish S, Goodman M, Wang CC (1976) Olfactory neuroblastoma. A clinical analysis of 17 cases. Cancer 37:1571–1576

    Google Scholar 

  • Kahn LB (1974) Esthesioneuroblastoma: a light- and electron-microscopic study. Hum Pathol 3:364–371

    Google Scholar 

  • Krausz T, Azzopardi JE, Pearse E (1984) Malignant melanoma of the sympathetic chain: with a consideration of pigmented nerve sheath tumors. Histopathology 8:881–894

    Google Scholar 

  • Llombart-Bosch A, Lacombe MJ, Contesso G, Peydro-Olaya A (1987) Small round blue cell sarcoma of bone mimicking atypical Ewing's sarcoma with neuroectodermal features. An analysis of five cases with immunohistochemical and electron microscopical support. Cancer 60:1570–1582

    Google Scholar 

  • Llombart-Bosch A, Carda C, Boix J, Pellin A, Peydro-Olaya A (1989) Value of nude mice xenografts in the expression of cell heterogeneity of human sarcomas of bone and soft tissue. Pathol Res and Pract

  • Llombart-Bosch A, Lacombe MJ, Peydro-Olaya A, Perez-Bacete M, Contesso G (1988) Malignant peripheral neuroectodermal tumors of bone other than Askin's neoplasm: characterization of 14 new cases with immunohistochemistry and electron microscopy. Virchows Arch [A] 412:421–430

    Google Scholar 

  • Lowman RM, Livolsi VA (1980) Pigmented (melanotic) Schwannomas of the spinal canal. Cancer 46:391–397

    Google Scholar 

  • Mackay B, Luna MA, Butler TJ (1976) Adult neuroblastoma. Electron microscopical observation of nine cases. Cancer 37:1334–1351

    Google Scholar 

  • Micheau C, Guerinot F, Bohvon C, Brugere J (1975) Dopamine beta-hydroxilase and cathecholamine in an olfatory esthesioneuroblastoma. Cancer 35:1309–1312

    Google Scholar 

  • Miller DC, Goodman M, Pilch BZ, Shi SR, Dickersin GR, Halpern H, Norris CM (1984) Mixed olfactory neuroblastoma and carcinoma. A report of two cases. Cancer 54:2019–2018

    Google Scholar 

  • Mills SE, Frierson HF (1985) Olfactory neuroblastoma. A clinicopathological study of 21 cases. Am J Surg Pathol 9:317–327

    Google Scholar 

  • Mullins JD (1980) A pigmented differentiating neuroblastoma: A light- and ultrasturctural study. Cancer 46:522–528

    Google Scholar 

  • Navas-Palacios JJ (1980) Malignant melanocytic neuroectodermal tumor. Cancer 46:529–536

    Google Scholar 

  • Newbill ET, Johns ME, Cantrell RW (1985) Esthesioneuroblastoma: Diagnosis and management. South Med J 78:275–282

    Google Scholar 

  • Ng HK, Poon WS, Poon WS, South JR (1988) Intraeranial olfactory neuroblastoma mimicking carcinoma: report of two cases. Histopathology 12:393–403

    Google Scholar 

  • Osamura RY, Fine G (1976) Ultrastructure of esthesioneuroblastoma. Cancer 38:173–179

    Google Scholar 

  • Osborn M, Altmannsberger M, Shaw G, Schauer A, Weber K (1982) Various sympathetic derived human tumors differ in neurofilament expression. Virchows Arch [B] 40:141–146

    Google Scholar 

  • Pedersen MI, Bennett JW, Wang N (1986) Non-random chromosome structural aberrations and oncogene loci in human malignant melanoma. Cancer Genet Cytogenet 20:11–27

    Google Scholar 

  • Rey JA, Bello MJ, Campos JM, Ramos MC, Benitez J (1985) Cytogenetic findings in a human malignant melanoma metastatic to the brain. Cancer Gen Cytogen 16:179–183

    Google Scholar 

  • Rode J, Dhillon AP (1984) Neuron specific anolase and S-100 protein as possible prognostic indicators in melanoma. Histopathology 8:1041–1052

    Google Scholar 

  • Sandberg AA, Turc-Carrel CL (1987) The cytogenetics of solid tumors. Cancer 59:387–395

    Google Scholar 

  • Sharkey FE, Fogh JM, Hajdu SJ, Fitzgerald P, Fogh JM (1978) Experiences in surgical pathology with human tumor growth in nude mice. In: Fogh J, Giovanella S (eds) The nude mouse in experimental and clinical research, vol. I, Academic Press, New York pp 187–214

    Google Scholar 

  • Sharkey FE, Spicer JM, Fogh J (1985) Changes in histological differentiation of human tumors transplanted into athymic nude mice: A morphometric study. Exp Cell Biol 53:100–106

    Google Scholar 

  • Silva EG, Butler JJ, Mackay B, Goepfert H (1982) Neuroblastomas and neuroendocrine carcinomas of the nasal cavity. A proposed new classification. Cancer 50:2388–2405

    Google Scholar 

  • Sternberger LA, Hardy PH Jr, Cuculis JJ, Meyer HG (1970) The unlabelled antibody enzyme method of immunohistochemistry: preparation and properties of soluble antigen-antibody complex (horseradish peroxidase-antihorseradish peroxidase) and its use in identification of spirochetes. J Histochem Cytochem 18:315–333

    Google Scholar 

  • Stirling RW, Powell G, Fletcher CDM (1988) Pigmented neuroectodermal tumor of infancy: an immunohistochemical study. Histopathology 12:425–435

    Google Scholar 

  • Taxy JB, Hidvegi DF (1977) Olfactory neuroblastoma. An ultrastructural study. Cancer 39:131–138

    Google Scholar 

  • Trojanowski JQ, Lee V, Pillsbury N, Lee S (1982) Neuronal origin of human esthesioneuroblastoma demonstrated with anti-neurofilament monoclonal antibodies. N Engl J Med 307:159–161

    Google Scholar 

  • Trojanowski JQ, Lee V, Leev MY, Schlaeper W (1984) An immunohistochemical study of human central and peripheral nervous system tumors, using monoclonal antibodies against neurofilaments and glial filaments. Hum Pathol 15:248–257

    Google Scholar 

  • Venable JH, Goggenshau R (1965) A simplified lead citrate stain for use in electron microscopy. J Cell Biol 25:407–408

    Google Scholar 

  • Vollruth N, Altmannsberger M, Hunneman DM et al. (1984) Esthesioneuroblastoma: Ultrastructural, immunohistochemical and biochemical investigation of one case. Arch Otorhinolaryngol 239:133–144

    Google Scholar 

  • Whang-Peng J, Freier RE, Knutsen T, Nanfro JJ, Gazdar A (1987) Translocation t(11;22) in esthesioneuroblastoma. Cancer Genet Cytogenet 29:155–157

    Google Scholar 

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This work has been supported, in part, with a grant (83/058) from the US-Spain Joint Committee for Scientific and Technological Cooperation (Madrid). This paper was presented, in abbreviated form, at the 72nd Tagung of the Deutsche Gesellschaft für Pathologie, Hannover (24–28 May, 1988)

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Llombart-Bosch, A., Carda, C., Peydro-Olaya, A. et al. Pigmented esthesioneuroblastoma showing dual differentiation following transplantation in nude mice. Vichows Archiv A Pathol Anat 414, 199–208 (1989). https://doi.org/10.1007/BF00822023

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