Primitive neuroectodermal tumor of the upper jaw

616 PRIMITIVE NEUROECTODERMAL TUMOR

References 1.

2.

3.

4.

5.

6.

Jones AC, Freedman PD, Kerpel SM: Oral adenoid squamous cell carcinoma: A report of three cases and review of the literature. J Oral Maxillofac Surg 51:676, 1993 Jacoway JR, Nelson JF, Boyers RC: Adenoid squamous-cell carcinoma of the lip (adenoacanthoma) of the oral labial mucosa: A clinicopathologic study of fifteen cases. Oral Surg Oral Med Oral Path01 32:444,1971 Tomich CE, Hutton CE: Adenoid squamous cell carcinoma of the lip: Report of cases. J Oral Surg 30:592, 1972 Weitzner S: Adenoid squamous-cell carcinoma of vermilion mucosa of lower lip. Oral Surg Oral Med Oral Path01 37:589, 1974 Caya JG, Hidayat AA, Weiner JM: A clinicopathologic study of 21 cases of adenoid squamous cell carcinoma of the eyelid and periorbital region. Am J Ophthalmol99:291, 1985 Lever WF: Adenoacanthoma of sweat glands: Carcinoma of sweat glands with glandular and epidermal elements. Report of four cases. Arch Dermatol Syphilol56:157, 1947

7.

8.

9.

10.

11.

12.

Muller SA, Wilhelmj CM Jr, Harrison EG Jr, et al: Adenoid squamous cell carcinoma (adenoacanthoma of Lever): Report of seven cases and review. Arch Dermatol89:589, 1964

Johnson WC, Helwig EB: Adenoid squamous cell carcinoma (adenoacanthoma): A clinicopathologic study of 155 patients. Cancer 19:1639,1966

Nappi 0, Pettinato G, Wick MR: Adenoid (acantholytic) squamous cell carcinoma of the skin. J Cutan Path01 16:855, 1986

Batsakis JG, Huser J: Squamous carcinomas with glandlike (adenoid) features. Ann Otol Rhino1 Laryngol99:87, 1990

Nappi 0, Wick MR, Pettinato G, et al: Pseudovascular adenoid squamous cell carcinoma of the skin: A neoplasm that may be mistaken for angiosarcoma. Am J Surg Path01 16:429, 1992

Langdon JD, Henk JM: Malignant Tumours of the Oral Cavity (ed 2). London, England, Arnold, 1993, p 157

J Oral Maxillofac Surg 57 616-620, 1999

Primitive Neuroectodermal Tumor of the Upper Jaw

Abel Garcz’a Garcia, MD, PhD, * Carlos Rodriguez-Pereira, MD, f Eugenio Perez-Becerra, MD, PbD,$ and Jose Manuel Gandara Rey, MD, PbD, DDSJ

Primitive neuroectodermal tumor (PNET) is an uncom- mon malignant neoplasim that was first described by Stout’ in 1918. Tumors of this type generally occur in young people and are equally common in both sexes. Diagnosis of PNET rests on histologic observation of a tumor consisting of small round cells, together with convincing ultrastructural and immunohistochemical evidence of divergent or incomplete glioneural differentiation.2 Treatment requires surgery, chemotherapy, and radiation therapy.

There have been few reports of PNET in the maxillofacial area.3x4 We report a case of PNET unusual in view of both its location and the patient’s age.

*Head of Section, Department of Maxillofacial Surgery, Complejo

Hospitalario Universitario de Santiago, and Professor of Maxillofa-

cial Surgery, University of Santiago de Compestela, Spain.

tResident, Department of Pathology, Complejo Hospitalario Uni-

versitario de Santiago, Santiago de Compestela, Spain.

*Staff and Professor, Department of Pathology, Complejo Hospi-

talario Universitario de Santiago, Santiago de Compestela, Spain.

§Professor of Oral Medicine, University of Santiago de Compes-

tela, Spain.

Address correspondence and reprint requests to Dr Garcia

Garcia: Facultad de Odontologia, Entrerrios s/n, Santiago de Compes-

tela, Spain; e-mail: [email protected]

0 1999 Amwcan Association of Oral and Maxillofacial Surgeons

027%2391/99/5705-002 1$3.00/O

Report of Case

A 77-year-old man was referred to us with a fast-growing tumor in the left palate, first noted 4 months previously. He had difficulty opening his mouth but did not report any pain. The tumor had a maximum diameter of about 5 cm and had caused swelling of the right hard palate and part of the right soft palate. It was soft. The mucosa was normal, without ulceration. Histologic examination of a biopsy specimen revealed a malignant neoplasm made up of a diffuse group of small round cells with scant cytoplasm and round vesicular nuclei with evident nucleoli (Figs 1, 2). Mitotic figures were frequent, as were areas of necrosis and hemorrhage. The tumor infiltrated deep into the soft tissues. Immunohisto- chemical tests showed binding by the monoclonal antibody (MAb) O-13 and by MAbs to vimentin, neuron-specific enolase (NSE), neurofilaments, and P2-microglobulin; by contrast, MAbs to cytokeratins, leukocyte common antigen (LCA), and desmin did not bind. Ultrastructural study showed cells with neuroendocrine granules, neuropil, and neural prolongations (Figs 3,4). All these findings suggested PNET. Computed tomography of the affected region showed a tumorous mass in the left upper jaw that was destroying osseous structures and invading soft tissues (Fig 5). Metasta- sis of the tumor was ruled out by conventional radiography, bone scintigraphy, and abdominal ultrasonography. The tumor was resected immediately, after the patient had refused radiation therapy or chemotherapy. Recurrence subsequently occurred, and the patient died 6 months later.

Discussion

A tumor of this type was first reported in 1918 by Stout,’ who described a malignant tumor in the arm

GARCIA GARCIA ET AL 617

FIGURE 1. Photomicrograph showing diffusely growing tumor not affecting the overlying mucosa (hematoxylin-eostn, original magnification X50).

FIGURE 3. Ultrastructure of the lesion. Well-defined areas of neuropil can be seen among the cell nests, together with numerous neural prolongations. These latter are 2 to 3 km in diameter and contain neuroendocrine granules (arrow). (Uranyl acetate, original magnification X4,000).

that he thought to have arisen from a peripheral nerve. The term PNET was first used by Hart and Earle5 in reference to a class of neoplasms occurring in children and composed of small cells showing various signs of maturation along neuronal, glial, or (more rarely) mesodermal lines. In vitro culture of these cells showed axon growth, arguing in favor of a neural

FIGURE 2. Photomicrograph showing diffuse proliferation of uniform small round cells. The nuclei are small, round or oval, and normochromatic. Sometimes a conspicuous nucleolus can be seen. Cells show scant cytoplasm (Hematoxylin-eosin, original magnification x500).

618 PRIMITIVE NEUROECTODERMAL TUMOR

FIGURE 4. Ultrastructure of the lesion. Detail of two closely apposed tumor cells, with cytoplasm containing ribosomes, fragments of rough endoplasmic reticulum, mitochondrta, and a few lipid inclusions (arrow). (Uranyl acetate, original magnification X8,000).

origin and suggesting a relationship with neuroblastoma. In 1979, Askin et al6 described a type of malignant small-cell tumor occurring in the thoracopulmonary region in children and adolescents. These authors performed a retrospective study of patients

FIGURE 5. Computed tomography image of the patient’s upper jaw. Arrows indicate the tumor and destruction of osseous tissues on the left side. UJ: upper jaw. M: mouth.

younger than 2 1 years and diagnosed over the period 1964 to 1976, who were suffering from small-cell tumors in the thoracopulmonary region. They found 20 cases of a small-cell tumor (subsequently named “Askin tumor”) that did not strictly meet the criteria for diagnosis as Ewing’s sarcoma (ES), lymphoma, rhabdomyosarcoma, or neuroblastoma. Tumors of this type were initially considered to have a neural origin. Subsequently, tumors with a similar histologic appear- ance were found in other locations, and awareness of this clinical entity grew.

In neuropathology, there are two approaches to the terminology for this group of tumors. The first approach holds that tumors occurring in different sites, although histologically similar, should be given different designations. The second approach is to call all such tumors PNETs, and then to add more specific qualifying.terms. Notably, PNETs can be divided into “undifferentiated” tumors (including the classical medulloblastoma) and “differentiating” tumors, including those displaying partial differentiation in one or more directions (Table l).’ Our case, a tumor originat- ing in a peripheral nerve, was an undifferentiated PNET.

Apart from the central nervous system, the thoracopulmonary region is the most frequent location for PNETs, followed by the extremities, the abdomen/ pelvis, and the head and neck region.8 In the latter region, there have been previous reports of involvement of the masseter muscle* and the maxillary sinus3

PNETs may arise at any age, though the incidence peaks during adolescence. In most studies, the mean age at detection has been between 11 and 22 years.6,g10 There is no evidence to suggest any between-sex difference in the incidence of PNETs.“,~

Clinical manifestations obviously depend on the location. In the case reported here, the symptoms simply reflected involvement of the palate by the tumor. In addition, local extension of the tumor leading to destruction of osseous tissues was observed, as has frequently been reported previously.6sJ1 From the clinical point of view, the dilferential diagnosis should consider other malignant neoplasms frequently occurring in the palate, notably epidermoid carcinoma, neoplasms of the minor salivary glands, and sarcomas (osteosarcoma).

Metastasis is observed at diagnosis in up to 31% of patients, reflecting the aggressiveness of tumors of this type. l 1 Commonly metastatic PNETs include those occurring in the lungs, bone, and bone marrow.

It is generally accepted that PNETs, as embryonic neoplasms, must be derived from fetal neuroepithelial cells (matrix cells), which are the precursors of all neurons, neuroglia, and ependymal cells.12 Histologic examination typically shows a homogeneous popula- tion of small round cells, with round hyperchromatic

Site

Cerebrum Cerebellum Brainstem Spinal cord Pineal gland Eye Olfactory nerve Peripheral nerve Adrenal gland

Neuroectodermal

Differentiation

Neural tube Neuronal Astrocytic Ependymal Pineal Retinal Olfactory Melanin Muscle Oligodendroglial Schwann cell Other

Standard Terminology

Medulloepithelioma Neuroblastoma Polar spongioblastoma Ependymoblastoma Pineoblastoma Retinoblastoma Neuroblastoma Melanotic medulloblastoma Myomedulloblastoma

No Differentiation

Primitive neuroectodermal tumor Medulloblastoma

Reprinted with permission from W.B. Saunders Company from Becker LE, Hinton D: Primitive neuroectodermal tumors of the central nervous system. Hum Path01 14:538, 1983.’

nuclei and scant cytoplasm. The cells can form sheets, trabeculae, or whorls but are more frequently ar- ranged in a diffuse infiltrating pattern. The tumor typically has a good blood supply and shows a high rate of mitosis. Areas of necrosis are usually present. There is sometimes histologic evidence of limited glial or neuronal differentiation.

Diagnosis of PNET presents some ditliculties. Micro- scopically, PNETs can be confused with rhabdomyosarcoma, ES, neuroblastoma, or lymphoma. Furthermore, the immunophenotype is typically polymorphous: PNETs may be labeled by the monoclonal antibody MB2, and by antibodies to vimentin, NSE (neuron- specific enolase), synaptophysin, neurofilaments, protein SlOO, and, occasionally, glial fibrillary acidic protein.13,14 In recent years, a new and relatively specific marker has been added to this panel, namely, the glycoprotein p30/32 MIC-2, encoded by the MIC-2 gene on the X and Y chromosomes. 15,r6 This antigen is recognized by various antibodies, two of which (HBA71 and O-13) are commercially available. The latter appears to be the most useful, because it labels nearly 100% of ESs and PNETs.” Strong labeling by O-13, together with desmin and LCA negativity, are strong evidence that a small-cell tumor is an ES or PNET.” However, cytogenetic studies have shown similar abnormalities in ES and PNET cells: specifi- cally, the t(l1;22)(q24;ql2) translocation considered specific for ES is also observed in PNET cells. This has led some authors to suggest that ES and PNET should be placed in the same category.‘*,‘9

Ultrastructural study of PNETs may show various features, not all of which need be present in a given tumor. These features include neuroendocrine gran-

ules, neuropil, neural prolongations (Figs 3,4), and filaments and microtubules.20-22

The case reported here showed the pleomorphic immunophenotype characteristic of PNET, with indi- cators of both mesodermal and neuronal differentiation (vimentin and NSE, respectively). Labeling by O-13, highly specific for ESs/PNETs, was also observed. Furthermore, ultrastructural study showed neurosecretory vesicles and scarce neurofilaments.

Current opinion with regard to treatment of PNET favors a multistrategy approach. Kushner et al” reported the experience of the Memorial Sloan-Ketter- ing Cancer Center in New York with regard to extracranial PNETs. Patients who had undergone resection of the tumor within 3 months of diagnosis showed improved survival. Radiation therapy (45 to 60 Gy) in combination with chemotherapy also has been reported to be effective for control of PNETs, although radiation therapy alone appears to be of little value.23.24 Drugs that have been used include cyclo- phosphamide, doxorubicin, anthracyclins, and alkyl- ant agents.23-25

The prognosis for patients with PNET is poor. Jones and McGilll’ reported that only 65% of their patients were alive within 2 years of diagnosis. Patients showing metastasis at diagnosis have even worse prospects of survival.

References 1. Stout AP: A tumor of the ulnar nerve. Proc NY Path01 Sot 18:L.

1918 2. Rosenblum MK: Central nervous system, in Rosai J (ed):

Ackerman’s Surgical Pathology (ed 8). Philadelphia, PA, Mosby, 1996, p 2318

620 RECURRENCE OF AN AMELOBLASTIC FIBRO-ODONTOMA

3. Filiatrault D, Jequier S, Brochu P: Pediatric case of the day: Primitive neuroectodermal tumor (PNET) of the right maxillary sinus. Radiographics 13:1397, 1993

4. Hollis LJ, Poole S, Hern J, et al: Primitive neuroectodermal tumour of the masseter muscle. J Laryngol Otol27:1179, 1996

5. Hart MN, Earle KM: Primitive neuroectodermal tumours of the brain in children Cancer 32890, 1973

6. Askin FB, Rosai J, Sibley RK, et al Malignant small cell tumor of the thoracopuhnanary region in childhood: A distinctive CR&O- pathologic entity of uncertain histogenesis. Cancer 43:2438, 1979

7. Becker LE, Hinton D: Primitive neuroectodermal tumors of the central nervous system. Hum Path01 14:538, 1983

8. Jfirgens H, Bier V, Harms D, et al: Malignant peripheral neuroectodermal tumors: A retrospective analysis of 42 patients. Cancer 61:349, 1988

9. Ashwal S, Hinshaw D: CNS primitive neuroectodermal tumors of childhood. Med Pediatr Oncol 12:180, 1984

10. Moerman P, Goddeeris P, Fryns J, et al: Primitive neuroectoder- ma1 tumor: A newly recognized cause of early fetal death. Pediatr Path01 4:137, 1985

11. Jones JE, McGill T: Peripheral primitive neuroectodermal tumors of the head and neck. Arch Otolaryngol Head Neck Surg 121:1392,1995

12. Fujita S: The matrix cell and cytogenesis in the developing central nervous system. J Comp Neurol 120:37, 1963

13. Ambros IM, Ambros PF, Strehl S, et al: MIC2 is a specific marker for Ewing’s sarcoma and peripheral primitive neuroectodermal tumors. Cancer 67:1886, 1991

14. Fellinger EJ, Garin-Chesa P, Triche TJ, et al: Immunohistochemi- cal analisys of Ewing’s sarcoma cell surface antigen p30/ 32MIC2. Am J Path01 139:317, 1991

15. Weidner N, Tjoe J: Immunohistochemical profile of monoclonal antibody O-13: Antibody that recognizes glycoprotein p30/32MIC2 and is useful in diagnosing Ewing’s sarcoma and peripheral neuroepithelioma. Am J Surg Path01 18:486, 1994

16. Shishikura A, Ushigome S, Shimoda T: Primitive neuroectodermal tumors of bone and soft tissue: Histological subclassilica- tion and clinicopathologic correlations. Acta Path01 Jpn 43:176, 1993

17. Dehner L: Primitive neuroectodermal tumor and Ewing sarcoma. Am J Surg Path01 17:1, 1993

18. Kahn HJ, Thormer PS: Monoclonal antibody MBL: A potential marker for Ewing’s sarcoma and primitive neuroectodermal tumors. Pediatr Path01 9:153, 1989

19. Kushner BH, Haydu S, Gulati SC: Extracranial primitive neuroectodermal tumors, Cancer 67:1825, 1991

20. Dehner L: Peripheral and central primitive neuroectodermal tumors: A nosologic concept seeking a consensus. Arch Path01 Lab Med 110:997,1986

21. Papierz W, Alwasiak J, Kolasa P, et al: Primitive neuroectodermal tumors: Ultrastructural and immunohistochemical studies, Ultrastruct Path01 19:147, 1995

22. Chowdhury K, Manoukian J, Rochou L, et al: Extracranial primitive neuroectodermal tumors of the head and neck. Arch Otolaryngol Head Neck Surg 116:475,1990

23. Miller JS, Kinsella T, Triche T, et al: Treatment of peripheral neurepitheliums in children and young adults. J Clin Oncol 5:1752, 1987

24. Shamberger R, Gier H, Weinstein H, et al: Chest wall tumors in infancy and childhood. Cancer 63:774,1989

25. Israel M, Miser J, Triche T, et al: Neuroepithelial tumors, in Pizza PA, Poplack DG (eds): Principles and Practice of Pediatric Oncology. Philadelphia, PA, Lippincott, 1989, pp 623-634

J Oral Maxillofac Surg 57:620-623, 1999

Recurrence of an Ameloblastic Fibro-Odontoma in a Y-Year-Old Boy

Ian Furst, DDS, *Michael Pharoah, DDS, MSc, FRCD(C), f

and John Phillips, MD, FRCS(C)f

The ameloblastic fibro-odontoma (AFO) is a rare mixed odontogenic tumor with similarities to the ameloblastic fibroma (AF) and ameloblastic denti- noma. There is considerable debate in the literature regarding the relationship between the AFO and the other mixed odontogenic tumors. Some argue that the AFO is a mature AF, and others believe it to be a precursor to the hamartomatous complex odontoma.

*Chief Resident, Oral & Maxillofacial Surgery, University of

Toronto, Toronto, Canada.

tHead, Department of Oral Radiology, Faculty of Dentisry,

University of Toronto, Toronto, Canada.

*Medical Director, Craniofacial Program, The Hospital for Sick

Children, Toronto, Canada.

Address correspondence and reprint requests to Dr Furst: 697

Coronation Blvd, Cambridge, Ontario, Canada NlR 3G5; e-mail:

[email protected]

Q 1999 Amertcon Association of Oral and Maxillofacia Surgeons

0278-239 l/99/5705-0022$3.00/0

These lesions consist of odontogenic epithelium and ectomesenchyme, with or without dental hard tissue formation. It has been described in the World Health Organization classification as “a lesion similar to ameloblas tic fibroma, but also showing inductive changes that lead to the formation of both dentine and enamel.“’

Although 86 cases of AFO have been reported in the world literature,* there have been no recurrences reported in these patients. Tsagaris3 did report one recurrence in 29 cases described in a Master’s thesis. Treatment for this rare lesion has ranged from wide excision* to enucleation with preservation of the involved tooth.5J8

We report a case of AFO treated with enucleation and preservation of the impacted tooth, and a subse- quent recurrence 2 years after initial treatment.

Report of Case

A -i-year-old boy was referred to the Craniofacial Program at the Hospital for Sick Children (Toronto, Canada) for evaluation of a lesion in his left mandible originally noticed

Documents

Primitive neuroectodermal tumor of the upper jaw