CASE REPORT
The Unexpected Finding of a Benign Mature Teratoma in a Forensic Pathology Autopsy A Rare Cause for Sudden, Unexpected Death Christian Bjerre Høyer, MD, PhD,* Benedicte Parm Ulhøi, MD,Þ and Annie Vesterby Charles, MD, DMSc*
Abstract: Intracranial teratomas are rare tumors that are usually discovered in infancy due to progressive symptoms. We describe a case of a 38-year-old man who was found dead 9 hours after the last sign of life. The deceased’s medical history could not explain the sudden, unexpected death. A forensic autopsy revealed an asymptomatic, mature teratoma in the left frontal and temporal lobes. We concluded that the cause of death must have been a generalized epileptiform seizure originating in the tumor site(s) leading to aspiration of the stomach contents and unfavorable positioning, resulting in asphyxia. Key Words: mature teratoma, sudden unexpected death, intracranial process (Am J Forensic Med Pathol 2013;34: 302Y305)
CASE REPORT A 38-year-old man was found unresponsive in a guestroom by his parents, who immediately called for an ambulance. Upon arrival, the ambulance crew pronounced the person dead because of the presence of rigor and livor mortis. The police found the deceased lying on the floor next to his bed, wrapped in bed linen and a duvet, with dark fluid leaking from his mouth. The body was positioned on the right side, almost prone, with the head resting on the chin and right shoulder, the right arm under the body, and the left arm outstretched anterior to the body. The police investigation of the scene showed no signs of foul play or reason to suspect an accident or suicide as the cause of death. The last sign of life was approximately 9 hours earlier; during the previous hours, he shared a couple of pizzas and a bottle of wine with his father and a friend of his father. The only health-related complaints of the evening were about ‘‘some uneasiness in the stomach’’ and plentiful flatulence.
pharmaceutical products, or illicit drugs. The deceased had suffered from modest hypercholesterolemia and a seasonal allergy to pollen, but he did not have a history of symptoms related to increased intracranial pressure (eg, headaches, loss of vision, impairment of the level of consciousness) or a focal neurological disease.
External Examination The examination of the body did not reveal any signs of trauma or disease.
Internal Examination There was no froth or any foreign object in the mouth or in the pharynx, and the tongue showed no signs of trauma (bite marks or contusions). The internal examination of the chest and abdomen revealed tracheal/bronchial aspiration of the stomach contents, pulmonary stasis and edema, atherosclerosis (fatty streaks), and hepatic steatosis.
Examination of the Brain The gross examination of the brain at autopsy revealed 2 distinct lesions: a tumor associated with the anterior cerebral artery (ACA) and a tumorous area on the medial and inferior surfaces of the left frontal lobe. The tumor adherent to the ACA was 0.7 cm in diameter (Fig. 1) with a firm but springy consistency. There was a defect in the cerebral tissue superior to the tumor and closely related to the superior aspect of the tumor (Fig. 2). The second lesion was a conglomerate of white granules up to 3 mm in diameter (Figs. 3 and 4). The area covered
POSTMORTEM EXAMINATION Medical History The deceased’s medical history could not explain the sudden, unexpected death. There was no history of abuse of alcohol, Manuscript received December 11, 2012; accepted May 17, 2013. From the *Department of Forensic Medicine, Section for Forensic Pathology and Clinical Forensic Medicine, Faculty of Health Sciences, Aarhus University, and †Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark. The authors report no conflicts of interest. The authors discussed the results and commented on the manuscript at all stages. Reprints: Christian Bjerre Høyer, MD, PhD, Department of Forensic Medicine, Section for Forensic Pathology and Clinical Forensic Medicine, Faculty of Health Sciences, Aarhus University, Denmark, Brendstrupgaardsvej 100, 8200 Aarhus N, Denmark. E-mail [email protected]. Copyright * 2013 by Lippincott Williams & Wilkins ISSN: 0195-7910/13/3404Y0302 DOI: 10.1097/PAF.0b013e3182a18983
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FIGURE 1. The cerebral arterial circle (circle of Willis). The tumor adherent to the left ACA (A) in relation to the right middle cerebral artery (B), the left middle cerebral artery (C), and the left posterior cerebral artery (D). Am J Forensic Med Pathol
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Volume 34, Number 4, December 2013
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Volume 34, Number 4, December 2013
FIGURE 2. The inferior surface of the left frontal lobe. The arrow points toward the concave grove corresponding to the location of the tumor adherent to the left ACA (Fig. 1). A metric ruler is shown.
was approximately 3.5 2.5 cm on the posteromedial part of the inferior surface of the left frontal lobe (Fig. 3), continuing medially and upward to include an additional area of approximately 2.0 1.5 cm (Fig. 4). The brain was fixed in formaldehyde solution in preparation for a neuropathological examination. The gross examination of the sliced, fixed brain showed destruction of the majority of the left temporal lobe by an approximately 2 3 4 cm tumor (Fig. 5). The tumor had a central cavity surrounded by walls consisting of cystic cavities (e3 mm) and white areas with a fatty appearance of the same size (Fig. 6). The opposing cerebral tissue in the frontal part of the left temporal lobe showed similar tissue changes, and the left cerebral sulcus was widened in the area between the lesions. Furthermore, approximately half of the putamen was destroyed by a large colloid cyst, and the demarcation of capsula interna was blurred.
Microscopic Examination
Benign Mature Teratoma in Autopsy
FIGURE 4. Macroscopic findings at autopsy. Relationship between the tumorous tissue on the medial side of the left frontal lobe (lifted aside) and the anterior part of the left temporal lobe (A), the optic chiasm (B), and the anterior part of the left frontal lobe (C). The brain is upside down with the right frontal lobe hidden by the metric ruler.
Paraffin sections of samples from the tumorous tissue in the left frontal lobe were HE stained and examined by light microscopy. The examination confirmed the presence of cysts of various sizes up to 3 mm in diameter (Fig. 7). Some of the cysts were close together, almost confluent, whereas others were separated by various amounts of glioneural tissue. The interior of the cysts was lined by a thin, stratified squamous epithelium, and the lumens were filled with keratin flakes. Neither goblet cells nor mucous cells were present in any of the cysts. Tissue samples were also subjected to immunohistochemical staining to detect cytokeratins (AE1/AE3, KL-1, CK8) and glial fibrillary acidic protein. The tumor cysts were lined with AE1/AE3-positive epithelium and keratin, had focal KL-1 positive areas, and were entirely CK8 negative (Fig. 8). The glioneural tissue consisted of low-cellularity swirls that were all glial fibrillary acidic protein positive. The tumor adherent to the ACA showed the same characteristics as described above for the tumorous areas. However, in addition to these characteristics, mature fat tissue was also found (Fig. 9). Based on these findings, the tumor was classified as a benign mature teratoma.
Paraffin sections of tissue samples from the lungs, heart, liver, kidney, and pancreas were stained with hematoxylin-eosin (HE) and examined by light microscopy. The examination of these tissue samples did not reveal any probable cause of death.
FIGURE 3. Macroscopic findings at autopsy. Relationship between the tumorous tissue at the inferior surface of the left frontal lobe (A) and the groove (B) corresponding to the tumor at the left ACA and the optic chiasm (C). The brain is lying upside down with the right frontal lobe hidden under the metric ruler. * 2013 Lippincott Williams & Wilkins
FIGURE 5. A coronal section of the fixed brain showing the main tumor in the left frontal lobe (A) and its relationship to the surrounding tissues; (B) right frontal lobe. A metric ruler is shown. www.amjforensicmedicine.com
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FIGURE 8. Cysts lined with keratin (AE1/3 positive) and full of keratin flakes (arrows) (cytokeratin immunostaining, original magnification 40). FIGURE 6. Detail from Figure 5 showing the tumor in the left frontal lobe (A), the widening of the interlobular sulcus (B), the tumorous tissue disseminating to the inferior surface of the left temporal lobe (C), the colloid cyst in the putamen (D), and the blurred demarcation of the left internal capsule (E) compared with that of the right internal capsule (F ).
Forensic Chemical Analysis The forensic chemical analysis showed a blood alcohol concentration of 7.8 mmol/L (0.36 mg/mL) but no pharmaceutical products or illicit drugs.
DISCUSSION The vast majority of sudden unexpected death due to intracranial, nontraumatic pathology has been reported to be related to epilepsy or spontaneous subarachnoid hemorrhages rather than intracranial tumors, which are described as rare.1 DiMaio and colleagues2 reviewed 10,995 consecutive medicolegal autopsies performed during the period of 1970Y1977 in Dallas County, Tex, and found that only 19 of them were cases of sudden, unexpected death due to intracranial neoplasms (0.17%), and only one of these was diagnosed as a teratoma.2 Eberhart and colleagues3 reviewed 54,873 forensic autopsies performed during the period of 1980-1999 in Maryland and found a mere 76 undiagnosed primary central nervous system tumors, none of which were teratomas.3 Intracranial teratomas comprise less than 0.5% of all intracranial tumors and are diagnosed predominantly at a young age (e15 years).4
FIGURE 7. Tumor tissue from the left frontal lobe with cysts of various sizes and shapes enclosed by glioneural tissue or in aggregates without interposed tissue (arrows) (HE staining, original magnification 20).
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Eberhart and colleagues3 have hypothesized that the growing use of computed tomography scanning and magnetic resonance imaging has increased the detection rate for intracranial tumors and consequently decreased the number of cases of sudden, unexpected death due to undiagnosed intracranial tumors. In this case, apparently no symptoms of an intracranial tumor existed before the death, neither symptoms of a spaceoccupying tumor nor focal symptoms. Considering the anatomical localization of the tumor, it would most likely produce only vague, unspecific symptoms (eg, impairment of learning or abstract thinking) that might even have been compensated for because of the slow growth (nonmalignant nature) of the tumor. Consequently, diagnosis of the tumor before death would have been virtually impossible, except as an unexpected finding of computed tomography scanning performed for another reason, such as trauma. The finding of an unexpected tumor always grants for detailed neuropathological examination to determine the exact type of pathology. In our case, possible differential diagnosis considered could be epidermoid cysts, but they are seldom multiple and seldom located inside the brain. The presence of multifocal epidermal cysts combined with the presence of fatty tissue and glioneural tissue in between gives the diagnosis in this case. Our conclusion is that the death was caused by the intracerebral mature teratoma, possibly due to a generalized epileptiform seizure resulting in the aspiration of stomach contents and unfavorable positioning leading to asphyxia. What is
FIGURE 9. Tumor tissue adherent to the ACA has the same characteristics as the rest of the tumorous tissue, including fatty tissue (arrows) (HE staining, original magnification 10). * 2013 Lippincott Williams & Wilkins
Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
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unusual in this case is the apparent lack of symptoms, the relatively old age of the deceased (38 years old), and the rarity of the type of tumor, which illustrates the importance of performing a forensic autopsy and a detailed histopathologic examination in cases of unexpected death. REFERENCES 1. Black M, Graham DI. Sudden unexplained death in adults caused by intracranial pathology. J Clin Pathol. 2002;55(1):44Y50.
* 2013 Lippincott Williams & Wilkins
Benign Mature Teratoma in Autopsy
2. DiMaio SM, DiMaio VJ, Kirkpatrick JB. Sudden, unexpected deaths due to primary intracranial neoplasms. Am J Forensic Med Pathol. 1980;1:29Y45. 3. Eberhart CG, Morrison A, Gyure KA, et al. Decreasing incidence of sudden death due to undiagnosed primary central nervous system tumors. Arch Pathol Lab Med. 2001;125(8):1024Y1030. 4. Tobias S, Valarezo J, Meir K, Umansky F. Giant cavernous sinus teratoma: a clinical example of a rare entity: case report. Neurosurgery. 2001;48(6):1367Y1370; discussion 1370Y1371.
www.amjforensicmedicine.com
Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
305
The Unexpected Finding of a Benign Mature Teratoma in a Forensic Pathology Autopsy A Rare Cause for Sudden, Unexpected Death Christian Bjerre Høyer, MD, PhD,* Benedicte Parm Ulhøi, MD,Þ and Annie Vesterby Charles, MD, DMSc*
Abstract: Intracranial teratomas are rare tumors that are usually discovered in infancy due to progressive symptoms. We describe a case of a 38-year-old man who was found dead 9 hours after the last sign of life. The deceased’s medical history could not explain the sudden, unexpected death. A forensic autopsy revealed an asymptomatic, mature teratoma in the left frontal and temporal lobes. We concluded that the cause of death must have been a generalized epileptiform seizure originating in the tumor site(s) leading to aspiration of the stomach contents and unfavorable positioning, resulting in asphyxia. Key Words: mature teratoma, sudden unexpected death, intracranial process (Am J Forensic Med Pathol 2013;34: 302Y305)
CASE REPORT A 38-year-old man was found unresponsive in a guestroom by his parents, who immediately called for an ambulance. Upon arrival, the ambulance crew pronounced the person dead because of the presence of rigor and livor mortis. The police found the deceased lying on the floor next to his bed, wrapped in bed linen and a duvet, with dark fluid leaking from his mouth. The body was positioned on the right side, almost prone, with the head resting on the chin and right shoulder, the right arm under the body, and the left arm outstretched anterior to the body. The police investigation of the scene showed no signs of foul play or reason to suspect an accident or suicide as the cause of death. The last sign of life was approximately 9 hours earlier; during the previous hours, he shared a couple of pizzas and a bottle of wine with his father and a friend of his father. The only health-related complaints of the evening were about ‘‘some uneasiness in the stomach’’ and plentiful flatulence.
pharmaceutical products, or illicit drugs. The deceased had suffered from modest hypercholesterolemia and a seasonal allergy to pollen, but he did not have a history of symptoms related to increased intracranial pressure (eg, headaches, loss of vision, impairment of the level of consciousness) or a focal neurological disease.
External Examination The examination of the body did not reveal any signs of trauma or disease.
Internal Examination There was no froth or any foreign object in the mouth or in the pharynx, and the tongue showed no signs of trauma (bite marks or contusions). The internal examination of the chest and abdomen revealed tracheal/bronchial aspiration of the stomach contents, pulmonary stasis and edema, atherosclerosis (fatty streaks), and hepatic steatosis.
Examination of the Brain The gross examination of the brain at autopsy revealed 2 distinct lesions: a tumor associated with the anterior cerebral artery (ACA) and a tumorous area on the medial and inferior surfaces of the left frontal lobe. The tumor adherent to the ACA was 0.7 cm in diameter (Fig. 1) with a firm but springy consistency. There was a defect in the cerebral tissue superior to the tumor and closely related to the superior aspect of the tumor (Fig. 2). The second lesion was a conglomerate of white granules up to 3 mm in diameter (Figs. 3 and 4). The area covered
POSTMORTEM EXAMINATION Medical History The deceased’s medical history could not explain the sudden, unexpected death. There was no history of abuse of alcohol, Manuscript received December 11, 2012; accepted May 17, 2013. From the *Department of Forensic Medicine, Section for Forensic Pathology and Clinical Forensic Medicine, Faculty of Health Sciences, Aarhus University, and †Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark. The authors report no conflicts of interest. The authors discussed the results and commented on the manuscript at all stages. Reprints: Christian Bjerre Høyer, MD, PhD, Department of Forensic Medicine, Section for Forensic Pathology and Clinical Forensic Medicine, Faculty of Health Sciences, Aarhus University, Denmark, Brendstrupgaardsvej 100, 8200 Aarhus N, Denmark. E-mail [email protected]. Copyright * 2013 by Lippincott Williams & Wilkins ISSN: 0195-7910/13/3404Y0302 DOI: 10.1097/PAF.0b013e3182a18983
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FIGURE 1. The cerebral arterial circle (circle of Willis). The tumor adherent to the left ACA (A) in relation to the right middle cerebral artery (B), the left middle cerebral artery (C), and the left posterior cerebral artery (D). Am J Forensic Med Pathol
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Volume 34, Number 4, December 2013
Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Am J Forensic Med Pathol
&
Volume 34, Number 4, December 2013
FIGURE 2. The inferior surface of the left frontal lobe. The arrow points toward the concave grove corresponding to the location of the tumor adherent to the left ACA (Fig. 1). A metric ruler is shown.
was approximately 3.5 2.5 cm on the posteromedial part of the inferior surface of the left frontal lobe (Fig. 3), continuing medially and upward to include an additional area of approximately 2.0 1.5 cm (Fig. 4). The brain was fixed in formaldehyde solution in preparation for a neuropathological examination. The gross examination of the sliced, fixed brain showed destruction of the majority of the left temporal lobe by an approximately 2 3 4 cm tumor (Fig. 5). The tumor had a central cavity surrounded by walls consisting of cystic cavities (e3 mm) and white areas with a fatty appearance of the same size (Fig. 6). The opposing cerebral tissue in the frontal part of the left temporal lobe showed similar tissue changes, and the left cerebral sulcus was widened in the area between the lesions. Furthermore, approximately half of the putamen was destroyed by a large colloid cyst, and the demarcation of capsula interna was blurred.
Microscopic Examination
Benign Mature Teratoma in Autopsy
FIGURE 4. Macroscopic findings at autopsy. Relationship between the tumorous tissue on the medial side of the left frontal lobe (lifted aside) and the anterior part of the left temporal lobe (A), the optic chiasm (B), and the anterior part of the left frontal lobe (C). The brain is upside down with the right frontal lobe hidden by the metric ruler.
Paraffin sections of samples from the tumorous tissue in the left frontal lobe were HE stained and examined by light microscopy. The examination confirmed the presence of cysts of various sizes up to 3 mm in diameter (Fig. 7). Some of the cysts were close together, almost confluent, whereas others were separated by various amounts of glioneural tissue. The interior of the cysts was lined by a thin, stratified squamous epithelium, and the lumens were filled with keratin flakes. Neither goblet cells nor mucous cells were present in any of the cysts. Tissue samples were also subjected to immunohistochemical staining to detect cytokeratins (AE1/AE3, KL-1, CK8) and glial fibrillary acidic protein. The tumor cysts were lined with AE1/AE3-positive epithelium and keratin, had focal KL-1 positive areas, and were entirely CK8 negative (Fig. 8). The glioneural tissue consisted of low-cellularity swirls that were all glial fibrillary acidic protein positive. The tumor adherent to the ACA showed the same characteristics as described above for the tumorous areas. However, in addition to these characteristics, mature fat tissue was also found (Fig. 9). Based on these findings, the tumor was classified as a benign mature teratoma.
Paraffin sections of tissue samples from the lungs, heart, liver, kidney, and pancreas were stained with hematoxylin-eosin (HE) and examined by light microscopy. The examination of these tissue samples did not reveal any probable cause of death.
FIGURE 3. Macroscopic findings at autopsy. Relationship between the tumorous tissue at the inferior surface of the left frontal lobe (A) and the groove (B) corresponding to the tumor at the left ACA and the optic chiasm (C). The brain is lying upside down with the right frontal lobe hidden under the metric ruler. * 2013 Lippincott Williams & Wilkins
FIGURE 5. A coronal section of the fixed brain showing the main tumor in the left frontal lobe (A) and its relationship to the surrounding tissues; (B) right frontal lobe. A metric ruler is shown. www.amjforensicmedicine.com
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FIGURE 8. Cysts lined with keratin (AE1/3 positive) and full of keratin flakes (arrows) (cytokeratin immunostaining, original magnification 40). FIGURE 6. Detail from Figure 5 showing the tumor in the left frontal lobe (A), the widening of the interlobular sulcus (B), the tumorous tissue disseminating to the inferior surface of the left temporal lobe (C), the colloid cyst in the putamen (D), and the blurred demarcation of the left internal capsule (E) compared with that of the right internal capsule (F ).
Forensic Chemical Analysis The forensic chemical analysis showed a blood alcohol concentration of 7.8 mmol/L (0.36 mg/mL) but no pharmaceutical products or illicit drugs.
DISCUSSION The vast majority of sudden unexpected death due to intracranial, nontraumatic pathology has been reported to be related to epilepsy or spontaneous subarachnoid hemorrhages rather than intracranial tumors, which are described as rare.1 DiMaio and colleagues2 reviewed 10,995 consecutive medicolegal autopsies performed during the period of 1970Y1977 in Dallas County, Tex, and found that only 19 of them were cases of sudden, unexpected death due to intracranial neoplasms (0.17%), and only one of these was diagnosed as a teratoma.2 Eberhart and colleagues3 reviewed 54,873 forensic autopsies performed during the period of 1980-1999 in Maryland and found a mere 76 undiagnosed primary central nervous system tumors, none of which were teratomas.3 Intracranial teratomas comprise less than 0.5% of all intracranial tumors and are diagnosed predominantly at a young age (e15 years).4
FIGURE 7. Tumor tissue from the left frontal lobe with cysts of various sizes and shapes enclosed by glioneural tissue or in aggregates without interposed tissue (arrows) (HE staining, original magnification 20).
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Eberhart and colleagues3 have hypothesized that the growing use of computed tomography scanning and magnetic resonance imaging has increased the detection rate for intracranial tumors and consequently decreased the number of cases of sudden, unexpected death due to undiagnosed intracranial tumors. In this case, apparently no symptoms of an intracranial tumor existed before the death, neither symptoms of a spaceoccupying tumor nor focal symptoms. Considering the anatomical localization of the tumor, it would most likely produce only vague, unspecific symptoms (eg, impairment of learning or abstract thinking) that might even have been compensated for because of the slow growth (nonmalignant nature) of the tumor. Consequently, diagnosis of the tumor before death would have been virtually impossible, except as an unexpected finding of computed tomography scanning performed for another reason, such as trauma. The finding of an unexpected tumor always grants for detailed neuropathological examination to determine the exact type of pathology. In our case, possible differential diagnosis considered could be epidermoid cysts, but they are seldom multiple and seldom located inside the brain. The presence of multifocal epidermal cysts combined with the presence of fatty tissue and glioneural tissue in between gives the diagnosis in this case. Our conclusion is that the death was caused by the intracerebral mature teratoma, possibly due to a generalized epileptiform seizure resulting in the aspiration of stomach contents and unfavorable positioning leading to asphyxia. What is
FIGURE 9. Tumor tissue adherent to the ACA has the same characteristics as the rest of the tumorous tissue, including fatty tissue (arrows) (HE staining, original magnification 10). * 2013 Lippincott Williams & Wilkins
Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
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unusual in this case is the apparent lack of symptoms, the relatively old age of the deceased (38 years old), and the rarity of the type of tumor, which illustrates the importance of performing a forensic autopsy and a detailed histopathologic examination in cases of unexpected death. REFERENCES 1. Black M, Graham DI. Sudden unexplained death in adults caused by intracranial pathology. J Clin Pathol. 2002;55(1):44Y50.
* 2013 Lippincott Williams & Wilkins
Benign Mature Teratoma in Autopsy
2. DiMaio SM, DiMaio VJ, Kirkpatrick JB. Sudden, unexpected deaths due to primary intracranial neoplasms. Am J Forensic Med Pathol. 1980;1:29Y45. 3. Eberhart CG, Morrison A, Gyure KA, et al. Decreasing incidence of sudden death due to undiagnosed primary central nervous system tumors. Arch Pathol Lab Med. 2001;125(8):1024Y1030. 4. Tobias S, Valarezo J, Meir K, Umansky F. Giant cavernous sinus teratoma: a clinical example of a rare entity: case report. Neurosurgery. 2001;48(6):1367Y1370; discussion 1370Y1371.
www.amjforensicmedicine.com
Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
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