Brain Pathology Case of the Month - April 2006



Melanotic neuroectodermal tumor of infancy (MNTI) is a rare, locally invasive neoplasm; typically arising in the cranial bones, especially the maxilla (2). Several synonyms have been applied for this distinctive lesion, including melanotic progonoma, congenital melanoma, retinal anlage tumor, congenital melanocarcinoma, and pigmented epulis of infancy (8). Infants of less than 1 year of age are commonly affected, with no gender preference (4, 8). Since the first description in 1918, approximately 200 MNTIs have been reported (4).

On gross examination, MNTI is a non-ulcerative lesion, with gray-brown cut surfaces. Expansion of the surrounding bone and invasion of the adjacent tissue are characteristic. Cytologic diagnosis is feasible, as demonstrated in our case. The dual populations of small neuroblast-like cells and large melanin-containing cells are the diagnostic hallmarks (4, 7). The presence of thick clusters of hyperplastic blood vessels also points towards the neuronal derivation, but, in order to identify the diagnostic cells, care should be taken to look for them in the background of smear. Analog to the cytologic appearances, two cellular components are demonstrable on the permanent section (2, 8). One consists of small round neoplastic cells, forming lobules intervened by fibrovascular septa. These round cells are embedded within a fine fibrillary matrix. The other is the melanin-containing large epithelial cell, with glandular or tubular arrangement. As in our case, mitotic activity is generally low, less than 2/10 high power field (1). The neuronal nature of small cell population is supported immunohistochemically and ultrastructurally by synaptophysin reactivity and the presence of neurosecretory granules, respectively (3, 6). The pigmented epithelial cells are stained positively with HMB-45 and contain cytoplasmic melanosomes, features supporting their melanocytic derivative (3, 6).

Because of its rarity, MNTI may be missed for other more common lesions. Differential diagnostic traps include infantile small round cell tumors, particularly embryonal rhabdomyosarcoma, neuroblastoma/primitive neuroectodermal tumor (PNET), and malignant lymphoma (4). The possibility of melanocytic lesions may also entertain given the presence of pigmented cells in MNTI (4). Nevertheless, as the histologic features of MNTI are highly characteristic, a correct diagnosis can be made even with the cytologic preparation provided the pathologist is aware of the entity.

Most MNTI is locally invasive, and usually controlled by surgical extirpation (2, 8). The aggressive melanotic medulloblastoma or other pigmented embryonal neuroepithelial tumors should not be regarded as MNTI (2). In support to this, a recent genetic study has failed to link MNTI with malignant small cell tumors such as neuroblastoma, peripheral PNET/Ewing's sarcoma, and desmoplastic small round cell tumor (5).


  1. Barrett AW, Morgan M, Ramsay AD, Farthing PM, Newman L, Speight PM. A clinicopathologic and immunohistochemical analysis of melanotic neuroectodermal tumor of infancy (2002) Oral Surg Oral Med Oral Pathol Oral Radiol Endod 93: 688-698.
  2. Burger PC, Scheithauer BW (1994) Tumors of the Central Nervous System. Atlas of Tumor Pathology, 3rd Series, Fascicle 10, pp 203, Armed Forces Institute of Pathology: Washington DC
  3. Claman LJ, Stetson D, Steinberg B, Shuler CF. Ultrastructural characteristics of a cell line derived from a melanotic neuroectodermal tumor of infancy (1991) J Oral Pathol Med 20: 245-249.
  4. Galera-Ruiz H, Gomez-Angel D, Vazquez-Ramirez FJ, Sanguino-Fabre JC, Salazar-Fernandez CI, Gonzalez-Hachero J. Fine needle aspiration in the pre- operative diagnosis of melanotic neuroectodermal tumour of infancy (1999). J laryngol Otol 113: 581-584.
  5. Khoddami M, Squire J, Zielenska M, Thorner P. Melanotic neuroectodermal tumor of infancy: a molecular genetic study (1998) Pediatr Dev Pathol 1: 295-259.
  6. Nelson ZL, Newman L, Loukota RA, Williams DM. Melanotic neuroectodermal tumor of infancy: an immunohistochemical and ultrastructural study (1995) Br J Oral Maxillofac Surg 33: 375-380.
  7. Rege JD, Shet T, Sawant HV, Naik LP (1999). Cytologic diagnosis of a melanotic neuroectodermal tumor of infancy occurring in the cranial bones. Diagn Cytopathol 21: 280-283.
  8. Weiss SW, Goldblum JR (2001) Enzinger and Weiss's Soft Tissue Tumors, 4th Edition, pp 1196-1200, Mosby: St. Louis

Contributed by Shanop Shuangshoti; Sukruthai Mujananon; Krishnapundha Bunyaratavej; Mookda Chaipipat; Surachai Khaoroptham

International Society of Neuropathology