Lymph node metastasis in spindle cell carcinoma arising in odontogenic cyst Report of a case Samir K. El-Mofty, DMD, PhD,a Michael Thomas A. Mustoe, MD,C St. Louis, MO.
T. Shannon, DMD.6 and
WASHINGTON UNIVERSITY, ST. LOUIS The majority of primary intraosseous carcinomas of the jaws develop in preexisting odontogenic cysts. These tumors are usually well-differentiated keratinizing carcinomas with relatively good prognosis. Only two of 41 previously reported acceptable cases of primary intraosseous carcinomas from ex-odontogenic cysts were associated with cervical lymph node metastasis. Spindle cell carcinoma is an anaplastic dimorphic neoplasm with poor prognosis. It has a special predilection for the upper aerodigestive tract. This is to our knowledge the first report of spindle cell carcinoma developing in an odontogenic cyst. Cervical lymph node metastasis showing typical histologic features of spindle cell carcinoma was detected 8 months postoperatively. The prognostic implications of this finding are discussed in light of previously reported cases of intraosseous carcinoma arising in odontogenic cysts and of spindle cell carcinoma of the oral cavity. (ORAL SURC ORAL MED ORAL PATHOL 1991;71:209-13)
A mong all the bones of the skeleton, the jaws have the unique distinction of harboring epithelial cells derived from the odontogenic tissues. These cells are subject to pathologic changesand frequently give rise to odontogenic cysts and benign tumors. Rarely, malignant epithelial tumors develop as primary intraosseouscarcinomas (PIOC). Thesejaw neoplasms arise either de novo or as a consequenceof malignant transformation of a previously existing cyst or tumor, The following classification of PIOC’3 * of the jaws was derived from that of the World Health Organization3 and is gaining more acceptance: 1. Arising from ex-odontogenic cyst 2. Arising from ex-ameloblastoma 3. Arising de novo To be acceptable as PIOC, all possibleextraosseous origins such as metastasis or direct extension from
aProfessor Oral Pathology, Washington University School of Medicine, St. Louis. bAssociate, Oral and Maxillofacial Surgery, Geisinger Medical Center, Danville, Pa.; formerly, Chief Resident, Oral and Maxillofacial Surgery, Washington University School of Dental Medicine, St. Louis. CAssistant Professor of Plastic Surgery, Department of Surgery, Washington University School of Medicine, St. Louis. 7/14/24081
nasal or antral carcinoma should be ruled out. In the case of carcinoma from an ex-odontogenic cyst, a preexisting cyst should be documented. Carcinoma arising in odontogenic cysts is a rare lesion, and the exact number of cases reported in the literature is difficult to determine. In 1959 Gardner4 accepted 25 well-documented cases; most of these were also included in later reviews, and 16 new caseshave been added since then.*, 5 Most of these cases were low grade keratinizing carcinomas with a favorable prognosis. Only two of the 41 reported cases showed spread to regional lymph nodes.5,6 In another case4a radiolucent lesion was detected in the pelvis of a patient 4 months after mandibular resection of carcinoma arising in a residual cyst; however, there was no further histologic documentation. Spindle cell carcinoma is an uncommon, poorly differentiated, bimorphic carcinoma whose histogenesis has been controversial. It has a predilection for the upper aerodigestive tract and usually results in a high rate of morbidity and mortality.’ To our knowledge, spindle cell carcinoma developing in the lining of an odontogenic cyst has not been previously reported. We report a case of spindle cell carcinoma arising in a residual odontogenic cyst of the maxilla, . m which subsequentlymph node metastasis was confirmed a few months postoperatively. 209
210
El-Lofty,
Shannon, and Mustoe
ORAL SLRG
ORAL MED ORAL PATHOI February 199I
Fig. 2. Occlusal radiograph shows radiolucent lesion involving periapical region of missing maxillary right lateral incisor.
dental radiograph shows well-demarcated and corticated radiolucency involving apex of carious maxillary right lateral incisor. Fig.
1. Periapical
CASEREPORT
A 47-year-old white man was seen in July 1987 with pain and swelling of the right anterior maxilla. The patient stated that the right maxillary lateral incisor was extracted 4 years previously because of a recurrent abscess that occurred intermittently during a lo-year period. Dental x-ray films taken in 1977 (Fig. 1) showed a well-demarcated unilocular cystic radiolucency with corticated margins. The lesion was located at the periapical area of the right lateral and central incisors. The patient was unaware of any further treatment, and no biopsy report was available. Since extraction of the incisor, the patient had no symptoms until May 1987; subsequently he noticed a swelling of the right anterior part of the maxilla. Clinical and radiographic examination revealed an expansile buccal swelling extending from the right maxillary canine to the left maxillary central incisor. This swelling was painful to palpation, but the mucosa was intact and normal. Neither palatal swelling nor mucosal irregularities could be detected. Radiographically, the lesion was unilocular with a well-defined corticated border (Fig. 2). It occupied the same location as the initial lesion (Fig. 1) that had been detected 10 years previously. There was no cervical lymphadenopathy. Medical history was significant for smoking more than one pack of cigarettes per day for many years and for alcohol abuse. Additionally, the patient had
mental impairment and a seizure disorder that resulted from a fall 3 years before initial presentation. With the patient under local anesthesia, aspiration yielded purulent exudate. Incision in the buccal vestibule was performed, and removal of a cystic lesion proceeded uneventfully. The specimen was submitted for microscopic examination, and diagnosis of poorly differentiated squamous cell carcinoma with spindle cell component arising in an odontogenic cyst was made. Chest x-ray films and computed tomographic scan of the head and neck revealed no other lesions. On July 8, 1987, anterior maxillectomy extending from the maxillary right first bicuspid to the maxillary left canine was performed. The patient tolerated the procedure well, and the postoperative course was uneventful. The patient continued to do well through follow-up visits, but 8 months postoperatively, on March 2, 1988, he was seen with an enlarged right midcervical jugular lymph node. The node was mobile and slightly tender. An aspiration biopsy was performed and revealed malignant cells consistent with epidermoid carcinoma. A thorough head and neck examination, and laryngoscopy, esophagoscopy, and bronchoscopy, were negative for evidence of any other primary tumors. On March 9, 1988, a modified radical neck dissection was performed. On microscopic examination one lymph node of 26 removed showed nonkeratinizing carcinoma with a spindle cell component. The patient was discharged, and no additional radiotherapy or chemotherapy was recommended. Two years after initial resection of the tumor, the patient is still well with no evidence of local, regional or systemic recurrence.
Volume Number
Spindle cell odontogenic carcinoma 2 I I
71 2
Fig. 4. Higher magnification of spindle cell carcinoma shows interlacing densefascicles of malignant spindle cells. (Hematoxylin-eosin stain; original magnification, X275.)
Fig. 3. Photomicrograph showsspindle cells dropping off from surface squamous cell carcinomatous component (top). Bottom halfof photomicrograph shows pseudosarcomatous proliferation of spindle cells. (Hematoxylin-eosin stain; original magnification, X90.) PATHOLOGIC
FINDINGS
The enucleated specimen was composedof several sheets of soft tissue, which was thickened and granular in someparts. It was submitted in its entirety for microscopic examination. The microscopic sections showed stratified squamous epithelial cyst lining and a thick, fibrous connective tissue wall. The epithelium appeared reactive in some areas and varied in thickness. Orthokeratinization and epithelial dysplasia were evident in parts of the lining. In other parts of the lining malignant neoplastic epithelium extended into the fibrous wall and into the lumen of the cyst. Keratin pearls and sheetsof malignant squamouscells were present at the surface (Fig. 3). Spindle cells seemed to drop off from the neoplastic surface epithelium (Fig. 3). These cells formed dense interlacing fascicles (Fig. 4) that comprised the main tumor mass in the fibrous wall. Transition of the squamous cell carcinoma to the sarcomatoid spindle
cell component was obvious (Fig. 3). The spindle cells had hyperchromatic large vesicular nuclei and prominent nucleoli. Mitotic activity was marked, and tumor cell necrosis was evident. The
Fig. 5. Microscopic section shows pericapsular area of lymph node containing proliferating tumor cells. Dense fascicles of spindle cells are interspersed with loosely arranged spindle and stellate cells. Wide intercellular gaps impart myxoid appearance.(Hematoxylin-eosin stain; original magnification, X 125.)
fibrous connective tissue stroma showedaggregatesof mixed inflammatory cells. The gross surgical specimenconsisted of a segment of the anterior maxilla. Serial sectioning of the specimen showed richly vascular fibrous connective tissue filling a bone cavity. Although a few foci of keratin were present, no tumor cells were seen. Microscopic examination of the metastatic lymph node (Fig. 5) showed proliferating tumor cells that obliterated its normal structure. The cells were predominantly spindle-shaped and stellate, with only a few foci of squamouscells. In areas of higher cellular density, spindle cells formed fascicles. In less dense locations spindle and stellate cells showed prominent intercellular spaces, producing a myxomatous appearance. Several multinucleated malignant tumor cells were present. Mitosis was marked, and large
212
El-Mofty,
Shannon, and Mustoe
6. Cytokeratin reactivity in spindle cell carcinoma arising in odontogenic cyst. (Peroxidase-antiperoxidase stain; original magnification, X275.) Fig.
areas of cellular necrosis were also present. The histologic findings were consistent with spindle cell carcinoma and resembled those of the primary tumor. Immunoperoxidase staining of paraffin sections from both primary and metastatic lesions showed reactivity for cytokeratin (Fig. 6) and epithelial membrane antigen. DISCUSSION
Ten years before the diagnosis of intraosseous carcinoma, the patient had periapical pathosis associated with the right maxillary lateral incisor. A dental x-ray film taken at that time was characteristic of periapical cyst. The tooth was subsequently extracted, but cyst removal was not documented. The development of a carcinoma in this location after a period of several years could be explained by either malignant transformation of the cyst lining or spread from local or remote primary carcinoma to the cyst. The intact oral, antral, and nasal mucosa, and the lack of evidencefor a remote primary tumor after a thorough physical and radiographic examination, are consistent with intraosseous origin. The development of carcinoma in a cyst lining has been further documented by the gross appearance of the enucleated lesion and microscopically by presence of dysplastic and nondysplastic cyst lining subjacent to the tumor site. The metastatic cervical lymph node, detected 8 months after surgical treatment, most likely represented lymphatic spread from the maxillary tumor rather than spread from another primary tumor. This is substantiated by thorough physical, radiographic, and computed tomographic examinations that failed to show evidence of another malignancy. Furthermore, both the tumor developing in the maxillary cyst and the one in the lymph node were spindle cell carcinomas. More than 60% of casesof carcinoma developing in
odontogenic cysts arise in inflammatory periapical or residual cysts294,8 Malignant transformation in follicular cysts occur less frequently, and carcinoma developing in lateral periodontal cyst9 or odontogenic keratocyst is rare. lo The time required for malignant transformation of cyst lining is not known; however, in many of these casesthe patient’s age or the time elapsed since extraction of the offending tooth are suggestive of a latency period of many years.?,‘. *, ” Radiographic examination does not always show malignant features. Many of these tumors, including the current case,are clinically presumed to be benign and are accordingly initially treated by conservative removal. The majority of the PIOC from ex-odontogenie cyst are highly differentiated keratinizing carcinomas4 and are relatively nonaggressive. Only two of the 4 1 acceptablecasereports document spread to cervical lymph nodes.5,6 None of the previously reported casesof carcinoma arising in odontogenic cysts has been described as spindle cell carcinoma; therefore the behavior and prognosis in such casesis unknown. Spindle cell carcinoma is an uncommon bimorphic tumor that occurs mainly in the upper aerodigestive tract. Histopathologically, these tumors show surface epithelial dysplasia or invasive squamous cell carcinoma in addition to an anaplastic pseudosarcomatous spindle cell component. The spindle cells form fascicles or are loosely arranged, producing a myxomatous pattern. Mitotic activity varies and can be marked. Pleomorphism, benign and malignant giant cells, and bone and cartilage formation have been described in these lesions and their metastases.7.‘*. I3 Current views support an epithelial origin of the spindle cells. This has been documented by immunohistochemical and electron microscopic studies.13sI4 In the current case the pseudosarcomatousspindle cell component was reactive for cytokeratin and epithelial membrane antigen. In a review of 59 casesof spindle cell carcinoma of the oral cavity from the files of the Armed Forces Institute of Pathology, Ellis and Coriols showedthat the most common sites of occurrence were the lip, tongue and gingiva, and alveolar mucosa. The prognosis in these caseswas generally poor. Twenty-five (55%) of the 45 patients who were followed up died of their disease.The mean survival time was lessthan 2 years. Histologic features had no predictive value, yet metastasiswas found to be the most reliable prognostic indicator. Surgery was found to be the most SUCcessful therapeutic modality, whereas radiation was ineffective. Accurate estimates of survival rate in cases of PIOC in ex-odontogenic cyst are not available becauseof the limited number of casesand lack of longterm follow-up. According to information derived
Spindle cell odontogenic carcinoma
Volume 7 1 Number 2
from 16 casesreported since 1970, the prognosis is relatively good.2*5 Ten patients (67%) were alive and well 1 to 6 years after the last treatment. Only three patients died of the tumor.536,l6 One of the patients who died of tumor had poorly differentiated squamous cell carcinoma with spread to cervical lymph nodes.6 Another patient5 had cervical metastasis at the time of surgery and died 1 year later of widely disseminated disease. According to this information, it might be possible to conclude that despite a limited number of reported cases, lymph node metastasis conveys an ominous prognostic significance. Additionally, metastasis to cervical lymph nodes is more likely to occur with poorly differentiated carcinoma. This is suggested by the observation that of the three cases59 6 of PIOC from ex-odontogenic cyst with metastasis to nodes, one tumor was poorly differentiated carcinoma, and in the present case an anaplastic spindle cell element prevailed. These findings also suggest that spindle cell carcinoma arising in an odontogenic cyst, like other spindle cell carcinomas of the oral cavity, is likely to behave aggressively, with higher rates of morbidity and mortality.
6. 7. 8. 9.
2I 3
PM. Squamous carcinoma arising in a dentigerous cyst: presentation of a fatal caseand review of four previously reported cases.ORAL SURG ORAL MED ORAL PATHOL 1970; 30:809- 16. Pearcey RG. Squamouscell carcinoma arising in dental cysts. Clin Radio1 1985;36:387-8. Appleman HD, Oberman HA. Squamouscell carcinoma of the larynx with sarcoma-like stroma. AMJ. Clin Path01 1965; 44:135-45. Eversole LR, Sabes WR, Rovin S. Aggressive growth and neoplastic potential of odontogeniccysts. Cancer 1975;35:27082. Baker RD, Onofrio ED, Corio RL, Crawford BE, Terry BC. Squamous cell carcinoma arising in a lateral periodontal cyst. ORAL SURG ORAL MED ORAL PATHOL 1979;47:495-9.
10. Areen RG, McClatchey KD, Baker HL. Squamous cell carcinoma developing in an odontogenickeratocyst. Arch Otolaryngo1 1981;107:568-9. 11. Van der Waal I, Rauhamaa R, Van der Kwast WAM, Snow GB. Squamous cell carcinoma arising in the lining of odontogenie cysts: report of 5 cases.Int J Oral Surg 1985;14:140-52. 12. Willis GW. Metastatic metaplastic carcinoma from pseudosarcoma of the mouth. South Med J 1977;70:1467-8. 13. Hyams VJ. Unusual tumors and lesions. In: Gnepp D, ed. Pathology of the head and neck. New York: Churchill Livingstone, 1988:459-95. 14. Tse JJ, Aughton W, Zirkin RM, Herman GE. Spindle cell carcinoma of the oral mucosa:casereport with immunoperoxidase and electron microscopic studies. J Oral Maxillofac Surg 1987;45:267-70. 15. Ellis GL, Corio RL. Spindle cell carcinoma of the oral cavity: a clinicopathologic assessmentof fifty-nine cases.ORAL SURG ORAL MED ORAL PATHOL 1980;50:523-34.
REFERENCES
1. Elzay RP. Primary intraosseouscarcinoma of the jaws. ORAL SURG ORAL MED ORAL PATHOL 1982;54:299-303.
2. Waldron CA, Mustoe TA. Primary intraosseouscarcinoma of the mandible with probable origin in an odontogenic cyst. ORAL SURG ORAL MED ORAL PATHOL 1989:67:716-24.
3. Pindborg JJ, Kramer IRH. Histologic typing of odontogenic tumors, cyst and allied lesion. Geneva: World Health Organization, 1971. 4. Gardner AF. The odontogenic cyst as a potential carcinoma: a clinicopathologic appraisal. J Am Dent Assoc 1969;78: 746-55. 5. Chretien PB, Carpenter DF, White NS, Harrah JD, Lightbody
16. Norris LV, Baghaei-Rad M, Maloney PL, Simpson G, Guinta J. Bilateral maxillary squamousodontogenic tumors and malignant transformation of a mandibular radiolucent lesion. J Oral Maxillofac Surg 1984;42:827-34. Reprint requests to:
Samir K. El-Mofty, DMD, PhD Professor of Oral Pathology Division of Surgical Pathology, Oral Pathology Section Washington University School of Medicine 1 Barnes Hospital Plaza St. Louis, MO 63110
T. Shannon, DMD.6 and
WASHINGTON UNIVERSITY, ST. LOUIS The majority of primary intraosseous carcinomas of the jaws develop in preexisting odontogenic cysts. These tumors are usually well-differentiated keratinizing carcinomas with relatively good prognosis. Only two of 41 previously reported acceptable cases of primary intraosseous carcinomas from ex-odontogenic cysts were associated with cervical lymph node metastasis. Spindle cell carcinoma is an anaplastic dimorphic neoplasm with poor prognosis. It has a special predilection for the upper aerodigestive tract. This is to our knowledge the first report of spindle cell carcinoma developing in an odontogenic cyst. Cervical lymph node metastasis showing typical histologic features of spindle cell carcinoma was detected 8 months postoperatively. The prognostic implications of this finding are discussed in light of previously reported cases of intraosseous carcinoma arising in odontogenic cysts and of spindle cell carcinoma of the oral cavity. (ORAL SURC ORAL MED ORAL PATHOL 1991;71:209-13)
A mong all the bones of the skeleton, the jaws have the unique distinction of harboring epithelial cells derived from the odontogenic tissues. These cells are subject to pathologic changesand frequently give rise to odontogenic cysts and benign tumors. Rarely, malignant epithelial tumors develop as primary intraosseouscarcinomas (PIOC). Thesejaw neoplasms arise either de novo or as a consequenceof malignant transformation of a previously existing cyst or tumor, The following classification of PIOC’3 * of the jaws was derived from that of the World Health Organization3 and is gaining more acceptance: 1. Arising from ex-odontogenic cyst 2. Arising from ex-ameloblastoma 3. Arising de novo To be acceptable as PIOC, all possibleextraosseous origins such as metastasis or direct extension from
aProfessor Oral Pathology, Washington University School of Medicine, St. Louis. bAssociate, Oral and Maxillofacial Surgery, Geisinger Medical Center, Danville, Pa.; formerly, Chief Resident, Oral and Maxillofacial Surgery, Washington University School of Dental Medicine, St. Louis. CAssistant Professor of Plastic Surgery, Department of Surgery, Washington University School of Medicine, St. Louis. 7/14/24081
nasal or antral carcinoma should be ruled out. In the case of carcinoma from an ex-odontogenic cyst, a preexisting cyst should be documented. Carcinoma arising in odontogenic cysts is a rare lesion, and the exact number of cases reported in the literature is difficult to determine. In 1959 Gardner4 accepted 25 well-documented cases; most of these were also included in later reviews, and 16 new caseshave been added since then.*, 5 Most of these cases were low grade keratinizing carcinomas with a favorable prognosis. Only two of the 41 reported cases showed spread to regional lymph nodes.5,6 In another case4a radiolucent lesion was detected in the pelvis of a patient 4 months after mandibular resection of carcinoma arising in a residual cyst; however, there was no further histologic documentation. Spindle cell carcinoma is an uncommon, poorly differentiated, bimorphic carcinoma whose histogenesis has been controversial. It has a predilection for the upper aerodigestive tract and usually results in a high rate of morbidity and mortality.’ To our knowledge, spindle cell carcinoma developing in the lining of an odontogenic cyst has not been previously reported. We report a case of spindle cell carcinoma arising in a residual odontogenic cyst of the maxilla, . m which subsequentlymph node metastasis was confirmed a few months postoperatively. 209
210
El-Lofty,
Shannon, and Mustoe
ORAL SLRG
ORAL MED ORAL PATHOI February 199I
Fig. 2. Occlusal radiograph shows radiolucent lesion involving periapical region of missing maxillary right lateral incisor.
dental radiograph shows well-demarcated and corticated radiolucency involving apex of carious maxillary right lateral incisor. Fig.
1. Periapical
CASEREPORT
A 47-year-old white man was seen in July 1987 with pain and swelling of the right anterior maxilla. The patient stated that the right maxillary lateral incisor was extracted 4 years previously because of a recurrent abscess that occurred intermittently during a lo-year period. Dental x-ray films taken in 1977 (Fig. 1) showed a well-demarcated unilocular cystic radiolucency with corticated margins. The lesion was located at the periapical area of the right lateral and central incisors. The patient was unaware of any further treatment, and no biopsy report was available. Since extraction of the incisor, the patient had no symptoms until May 1987; subsequently he noticed a swelling of the right anterior part of the maxilla. Clinical and radiographic examination revealed an expansile buccal swelling extending from the right maxillary canine to the left maxillary central incisor. This swelling was painful to palpation, but the mucosa was intact and normal. Neither palatal swelling nor mucosal irregularities could be detected. Radiographically, the lesion was unilocular with a well-defined corticated border (Fig. 2). It occupied the same location as the initial lesion (Fig. 1) that had been detected 10 years previously. There was no cervical lymphadenopathy. Medical history was significant for smoking more than one pack of cigarettes per day for many years and for alcohol abuse. Additionally, the patient had
mental impairment and a seizure disorder that resulted from a fall 3 years before initial presentation. With the patient under local anesthesia, aspiration yielded purulent exudate. Incision in the buccal vestibule was performed, and removal of a cystic lesion proceeded uneventfully. The specimen was submitted for microscopic examination, and diagnosis of poorly differentiated squamous cell carcinoma with spindle cell component arising in an odontogenic cyst was made. Chest x-ray films and computed tomographic scan of the head and neck revealed no other lesions. On July 8, 1987, anterior maxillectomy extending from the maxillary right first bicuspid to the maxillary left canine was performed. The patient tolerated the procedure well, and the postoperative course was uneventful. The patient continued to do well through follow-up visits, but 8 months postoperatively, on March 2, 1988, he was seen with an enlarged right midcervical jugular lymph node. The node was mobile and slightly tender. An aspiration biopsy was performed and revealed malignant cells consistent with epidermoid carcinoma. A thorough head and neck examination, and laryngoscopy, esophagoscopy, and bronchoscopy, were negative for evidence of any other primary tumors. On March 9, 1988, a modified radical neck dissection was performed. On microscopic examination one lymph node of 26 removed showed nonkeratinizing carcinoma with a spindle cell component. The patient was discharged, and no additional radiotherapy or chemotherapy was recommended. Two years after initial resection of the tumor, the patient is still well with no evidence of local, regional or systemic recurrence.
Volume Number
Spindle cell odontogenic carcinoma 2 I I
71 2
Fig. 4. Higher magnification of spindle cell carcinoma shows interlacing densefascicles of malignant spindle cells. (Hematoxylin-eosin stain; original magnification, X275.)
Fig. 3. Photomicrograph showsspindle cells dropping off from surface squamous cell carcinomatous component (top). Bottom halfof photomicrograph shows pseudosarcomatous proliferation of spindle cells. (Hematoxylin-eosin stain; original magnification, X90.) PATHOLOGIC
FINDINGS
The enucleated specimen was composedof several sheets of soft tissue, which was thickened and granular in someparts. It was submitted in its entirety for microscopic examination. The microscopic sections showed stratified squamous epithelial cyst lining and a thick, fibrous connective tissue wall. The epithelium appeared reactive in some areas and varied in thickness. Orthokeratinization and epithelial dysplasia were evident in parts of the lining. In other parts of the lining malignant neoplastic epithelium extended into the fibrous wall and into the lumen of the cyst. Keratin pearls and sheetsof malignant squamouscells were present at the surface (Fig. 3). Spindle cells seemed to drop off from the neoplastic surface epithelium (Fig. 3). These cells formed dense interlacing fascicles (Fig. 4) that comprised the main tumor mass in the fibrous wall. Transition of the squamous cell carcinoma to the sarcomatoid spindle
cell component was obvious (Fig. 3). The spindle cells had hyperchromatic large vesicular nuclei and prominent nucleoli. Mitotic activity was marked, and tumor cell necrosis was evident. The
Fig. 5. Microscopic section shows pericapsular area of lymph node containing proliferating tumor cells. Dense fascicles of spindle cells are interspersed with loosely arranged spindle and stellate cells. Wide intercellular gaps impart myxoid appearance.(Hematoxylin-eosin stain; original magnification, X 125.)
fibrous connective tissue stroma showedaggregatesof mixed inflammatory cells. The gross surgical specimenconsisted of a segment of the anterior maxilla. Serial sectioning of the specimen showed richly vascular fibrous connective tissue filling a bone cavity. Although a few foci of keratin were present, no tumor cells were seen. Microscopic examination of the metastatic lymph node (Fig. 5) showed proliferating tumor cells that obliterated its normal structure. The cells were predominantly spindle-shaped and stellate, with only a few foci of squamouscells. In areas of higher cellular density, spindle cells formed fascicles. In less dense locations spindle and stellate cells showed prominent intercellular spaces, producing a myxomatous appearance. Several multinucleated malignant tumor cells were present. Mitosis was marked, and large
212
El-Mofty,
Shannon, and Mustoe
6. Cytokeratin reactivity in spindle cell carcinoma arising in odontogenic cyst. (Peroxidase-antiperoxidase stain; original magnification, X275.) Fig.
areas of cellular necrosis were also present. The histologic findings were consistent with spindle cell carcinoma and resembled those of the primary tumor. Immunoperoxidase staining of paraffin sections from both primary and metastatic lesions showed reactivity for cytokeratin (Fig. 6) and epithelial membrane antigen. DISCUSSION
Ten years before the diagnosis of intraosseous carcinoma, the patient had periapical pathosis associated with the right maxillary lateral incisor. A dental x-ray film taken at that time was characteristic of periapical cyst. The tooth was subsequently extracted, but cyst removal was not documented. The development of a carcinoma in this location after a period of several years could be explained by either malignant transformation of the cyst lining or spread from local or remote primary carcinoma to the cyst. The intact oral, antral, and nasal mucosa, and the lack of evidencefor a remote primary tumor after a thorough physical and radiographic examination, are consistent with intraosseous origin. The development of carcinoma in a cyst lining has been further documented by the gross appearance of the enucleated lesion and microscopically by presence of dysplastic and nondysplastic cyst lining subjacent to the tumor site. The metastatic cervical lymph node, detected 8 months after surgical treatment, most likely represented lymphatic spread from the maxillary tumor rather than spread from another primary tumor. This is substantiated by thorough physical, radiographic, and computed tomographic examinations that failed to show evidence of another malignancy. Furthermore, both the tumor developing in the maxillary cyst and the one in the lymph node were spindle cell carcinomas. More than 60% of casesof carcinoma developing in
odontogenic cysts arise in inflammatory periapical or residual cysts294,8 Malignant transformation in follicular cysts occur less frequently, and carcinoma developing in lateral periodontal cyst9 or odontogenic keratocyst is rare. lo The time required for malignant transformation of cyst lining is not known; however, in many of these casesthe patient’s age or the time elapsed since extraction of the offending tooth are suggestive of a latency period of many years.?,‘. *, ” Radiographic examination does not always show malignant features. Many of these tumors, including the current case,are clinically presumed to be benign and are accordingly initially treated by conservative removal. The majority of the PIOC from ex-odontogenie cyst are highly differentiated keratinizing carcinomas4 and are relatively nonaggressive. Only two of the 4 1 acceptablecasereports document spread to cervical lymph nodes.5,6 None of the previously reported casesof carcinoma arising in odontogenic cysts has been described as spindle cell carcinoma; therefore the behavior and prognosis in such casesis unknown. Spindle cell carcinoma is an uncommon bimorphic tumor that occurs mainly in the upper aerodigestive tract. Histopathologically, these tumors show surface epithelial dysplasia or invasive squamous cell carcinoma in addition to an anaplastic pseudosarcomatous spindle cell component. The spindle cells form fascicles or are loosely arranged, producing a myxomatous pattern. Mitotic activity varies and can be marked. Pleomorphism, benign and malignant giant cells, and bone and cartilage formation have been described in these lesions and their metastases.7.‘*. I3 Current views support an epithelial origin of the spindle cells. This has been documented by immunohistochemical and electron microscopic studies.13sI4 In the current case the pseudosarcomatousspindle cell component was reactive for cytokeratin and epithelial membrane antigen. In a review of 59 casesof spindle cell carcinoma of the oral cavity from the files of the Armed Forces Institute of Pathology, Ellis and Coriols showedthat the most common sites of occurrence were the lip, tongue and gingiva, and alveolar mucosa. The prognosis in these caseswas generally poor. Twenty-five (55%) of the 45 patients who were followed up died of their disease.The mean survival time was lessthan 2 years. Histologic features had no predictive value, yet metastasiswas found to be the most reliable prognostic indicator. Surgery was found to be the most SUCcessful therapeutic modality, whereas radiation was ineffective. Accurate estimates of survival rate in cases of PIOC in ex-odontogenic cyst are not available becauseof the limited number of casesand lack of longterm follow-up. According to information derived
Spindle cell odontogenic carcinoma
Volume 7 1 Number 2
from 16 casesreported since 1970, the prognosis is relatively good.2*5 Ten patients (67%) were alive and well 1 to 6 years after the last treatment. Only three patients died of the tumor.536,l6 One of the patients who died of tumor had poorly differentiated squamous cell carcinoma with spread to cervical lymph nodes.6 Another patient5 had cervical metastasis at the time of surgery and died 1 year later of widely disseminated disease. According to this information, it might be possible to conclude that despite a limited number of reported cases, lymph node metastasis conveys an ominous prognostic significance. Additionally, metastasis to cervical lymph nodes is more likely to occur with poorly differentiated carcinoma. This is suggested by the observation that of the three cases59 6 of PIOC from ex-odontogenic cyst with metastasis to nodes, one tumor was poorly differentiated carcinoma, and in the present case an anaplastic spindle cell element prevailed. These findings also suggest that spindle cell carcinoma arising in an odontogenic cyst, like other spindle cell carcinomas of the oral cavity, is likely to behave aggressively, with higher rates of morbidity and mortality.
6. 7. 8. 9.
2I 3
PM. Squamous carcinoma arising in a dentigerous cyst: presentation of a fatal caseand review of four previously reported cases.ORAL SURG ORAL MED ORAL PATHOL 1970; 30:809- 16. Pearcey RG. Squamouscell carcinoma arising in dental cysts. Clin Radio1 1985;36:387-8. Appleman HD, Oberman HA. Squamouscell carcinoma of the larynx with sarcoma-like stroma. AMJ. Clin Path01 1965; 44:135-45. Eversole LR, Sabes WR, Rovin S. Aggressive growth and neoplastic potential of odontogeniccysts. Cancer 1975;35:27082. Baker RD, Onofrio ED, Corio RL, Crawford BE, Terry BC. Squamous cell carcinoma arising in a lateral periodontal cyst. ORAL SURG ORAL MED ORAL PATHOL 1979;47:495-9.
10. Areen RG, McClatchey KD, Baker HL. Squamous cell carcinoma developing in an odontogenickeratocyst. Arch Otolaryngo1 1981;107:568-9. 11. Van der Waal I, Rauhamaa R, Van der Kwast WAM, Snow GB. Squamous cell carcinoma arising in the lining of odontogenie cysts: report of 5 cases.Int J Oral Surg 1985;14:140-52. 12. Willis GW. Metastatic metaplastic carcinoma from pseudosarcoma of the mouth. South Med J 1977;70:1467-8. 13. Hyams VJ. Unusual tumors and lesions. In: Gnepp D, ed. Pathology of the head and neck. New York: Churchill Livingstone, 1988:459-95. 14. Tse JJ, Aughton W, Zirkin RM, Herman GE. Spindle cell carcinoma of the oral mucosa:casereport with immunoperoxidase and electron microscopic studies. J Oral Maxillofac Surg 1987;45:267-70. 15. Ellis GL, Corio RL. Spindle cell carcinoma of the oral cavity: a clinicopathologic assessmentof fifty-nine cases.ORAL SURG ORAL MED ORAL PATHOL 1980;50:523-34.
REFERENCES
1. Elzay RP. Primary intraosseouscarcinoma of the jaws. ORAL SURG ORAL MED ORAL PATHOL 1982;54:299-303.
2. Waldron CA, Mustoe TA. Primary intraosseouscarcinoma of the mandible with probable origin in an odontogenic cyst. ORAL SURG ORAL MED ORAL PATHOL 1989:67:716-24.
3. Pindborg JJ, Kramer IRH. Histologic typing of odontogenic tumors, cyst and allied lesion. Geneva: World Health Organization, 1971. 4. Gardner AF. The odontogenic cyst as a potential carcinoma: a clinicopathologic appraisal. J Am Dent Assoc 1969;78: 746-55. 5. Chretien PB, Carpenter DF, White NS, Harrah JD, Lightbody
16. Norris LV, Baghaei-Rad M, Maloney PL, Simpson G, Guinta J. Bilateral maxillary squamousodontogenic tumors and malignant transformation of a mandibular radiolucent lesion. J Oral Maxillofac Surg 1984;42:827-34. Reprint requests to:
Samir K. El-Mofty, DMD, PhD Professor of Oral Pathology Division of Surgical Pathology, Oral Pathology Section Washington University School of Medicine 1 Barnes Hospital Plaza St. Louis, MO 63110
