- Email: [email protected]
Mature Teratoma in a Supernumerary Ovary in a Child: Report of the First Case
Accepted Manuscript Mature teratoma in a supernumerary ovary in a child: report of the first case Ruchika Gupta, M.D, Sarika Verma, D.N.B, Kalpana Bansal, M.D, Vishesh Jain, M.S, M.Ch, Mamta Sengar, M.S., M.Ch, Anup Mohta, M.S, M.Ch PII:
S1083-3188(15)00265-X
DOI:
10.1016/j.jpag.2015.07.005
Reference:
PEDADO 1878
To appear in:
Journal of Pediatric and Adolescent Gynecology
Received Date: 22 January 2015 Revised Date:
29 July 2015
Accepted Date: 29 July 2015
Please cite this article as: Gupta R, Verma S, Bansal K, Jain V, Sengar M, Mohta A, Mature teratoma in a supernumerary ovary in a child: report of the first case, Journal of Pediatric and Adolescent Gynecology (2015), doi: 10.1016/j.jpag.2015.07.005. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Title: Mature teratoma in a supernumerary ovary in a child: report of the first case Authors: Ruchika Gupta, M.D.*1, Sarika Verma D.N.B.**1, Kalpana Bansal, M.D.*2, Vishesh Jain,
*Assistant Professor, **Senior Resident, ***Professor
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M.S., M.Ch.*3, Mamta Sengar, M.S., M.Ch.*3, Anup Mohta, M.S., M.Ch.***3
Departments of 1Pathology, 2Radiodiagnosis and 3Pediatric Surgery
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Chacha Nehru Bal Chikitsalaya
Delhi – 110031, India
Address for Correspondence: Dr. Ruchika Gupta
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Assistant Professor & HOD
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Geeta Colony
Department of Pathology
Chacha Nehru Bal Chikitsalaya
India
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Delhi – 110031
EP
Geeta Colony
Ph: +91-9643308237
E-mail: [email protected] Source of financial support: None
1
ACCEPTED MANUSCRIPT
ABSTRACT Background: Supernumerary ovary, i.e. ovarian ectopia having no anatomic connection with the normally placed ovaries, is a rare gynecologic condition. To the best
RI PT
of our knowledge, only one pediatric case of supernumerary ovary has been reported to date in the English literature.
Case: A four-year girl was assessed for foul-smelling vestibular discharge and found to
SC
have a fistulous tract with opening near the vaginal orifice. Fistuloscopy revealed hair in the lumen of the tract. Computed tomography scan showed a retroperitoneal mass in
retroperitoneal supernumerary ovary.
M AN U
continuation of the tract. Excision of the mass revealed a mature teratoma in a
Conclusion: Supernumerary ovary, a gynecologic rarity, is even more uncommon in children. Hence, a thorough clinic-radiological-pathological correlation is mandatory to
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diagnose extragonadal ovarian tumors arising in supernumerary ovaries.
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EP
Key Words: Supernumerary, Ovary, Mature teratoma, Retroperitoneum, Pediatric
2
ACCEPTED MANUSCRIPT
INTRODUCTION Supernumerary ovary is a gynecologic rarity, which needs to be differentiated from accessory ovary in that the former has no anatomical connection with the normally
RI PT
located ovaries.1 It has been suggested recently to include both supernumerary and accessory ovaries in the term ‘ectopic ovary’.2 An extensive review of the available indexed English literature revealed about 30 cases of supernumerary ovaries, mainly in
been reported so far in the available literature.5
SC
adults with a wide age range.3,4 Only one case of supernumerary ovary in a child has
M AN U
The embryology of supernumerary ovary has been discussed in detail by Printz et al, suggesting migratory arrest of gonocytes or germinal ridge transplant as the possible hypotheses leading to this phenomenon.6 Cases of surface epithelial tumors as well as germ cell tumors (teratoma) have been reported in supernumerary ovaries.4,7,8
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This report describes the case of a young girl with mature teratoma arising in a supernumerary ovary and presenting as vestibular discharge. This is the second
AC C
EP
pediatric report of supernumerary ovary, to the best of our knowledge.
3
ACCEPTED MANUSCRIPT
CASE A four-year-old girl presented with foul-smelling vestibular discharge for the last two years. There were no associated urinary complaints or history of bloody discharge. No
RI PT
significant medical or surgical history was present. Local examination revealed a small opening in the vestibule on the left side of vaginal orifice. A fine feeding tube could be inserted in the opening for 2-3 cm inside. The anus was normal and no rectovestibular
SC
fistula was detected.
Fistulogram through the opening revealed a blind ending tract in the pelvis. The tract
M AN U
was not communicating with the rectum. An examination under anesthesia with endoscopy was planned. The opening did not allow no. 5 cystoscope. However, after dissection of the tract for 3 cm from perineal end, the tract widened and a no. 7 cystoscope was easily inserted in the tract. Endoscopy revealed presence of hair inside
TE D
the lumen. The dissected end of the tract was sutured to the perineum and a computed tomography scan (CT scan) performed.
Computed tomography (CT) scan revealed a contrast-opacified long tubular sinus tract
EP
extending intra-abdominally from right lateral vestibular opening to the D9 vertebral level leading into a well-defined lobulated retroperitoneal soft tissue mass with intralesional
AC C
fat and bony component (Fig. 1 and 2), the latter being connected to D9-D11 vertebral bodies which appeared fused (block vertebra). Alpha-fetoprotein levels (AFP) of the child were within normal range. The child was planned for exploratory laparotomy and excision of the tract and the mass. Intra-operatively, the tract was seen to extend superiorly in the midline ending in a mass lying just above the isthmus of a horseshoe
4
ACCEPTED MANUSCRIPT
kidney. A bony extension was seen from the mass to the vertebra and was divided flush with the vertebra. Bilateral normal ovaries were present in the pelvis. We received a specimen of irregular globular soft tissue mass measuring 4x3x2 cm with
RI PT
attached tubular structure, 10 cm long. The mass, on cut-section, was homogenous yellow-white with focal gritty areas and a small cyst, 1 cm in diameter.
The soft tissue was processed in entirety in multiple sections. Histologic sections from
SC
the cystic area showed normal ovarian parenchyma with primordial follicles (Fig. 3a). Sections from rest of the mass showed features of a mature teratoma composed of
M AN U
epidermis, skeletal muscle, cartilage, bony trabeculae and marrow tissue (Fig. 3b-d). Immature elements were not seen in any of the sections. A review of the CT findings by the radiologist confirmed the presence of eutopic ovaries in addition to this mass. Hence, a final pathologic diagnosis was mature teratoma arising in a supernumerary
TE D
ovary.
The postoperative period of the child was uneventful. The child has been recurrencefree in one year of follow-up. She is also being evaluated for vertebral anomalies and
AC C
EP
scoliosis by the orthopedic surgeon.
5
ACCEPTED MANUSCRIPT
SUMMARY & CONCLUSION Supernumerary ovary is a rare gynecologic condition and is usually detected incidentally. Differentiation needs to be made from 'accessory ovary', in which extra
RI PT
ovarian tissue is placed near the normally placed ovary and is usually connected to the normal ovary. On the other hand, supernumerary ovary, as described by Wharton in 1959, includes those rare cases of ectopia where the third ovary is entirely separate
SC
from normally located ovary and apparently arises from a separate primordium.1 Lachman has suggested that the term 'ectopic ovary' should replace the terms
M AN U
supernumerary and accessory ovary and be defined as any ovarian tissue additional to normal ovaries.2 An extensive review of the available indexed English literature revealed about 30 reported cases of supernumerary ovaries, primarily in adults. The age range of previously reported cases of supernumerary ovaries has been wide,
TE D
from 17 years through 80 years. Supernumerary ovaries are rare in children. An extensive review of the available indexed English literature revealed only one previously reported case of supernumerary ovary in a 5-year-old child.5 Our case is the second
EP
report of supernumerary ovary in a child and first pediatric report of mature teratoma in a supernumerary ovary. Most of the cases have been asymptomatic, detected on
AC C
autopsy or incidentally at laparotomy. Only in rare cases, supernumerary ovary was suspected pre-operatively, primarily due to menstrual bleeding after bilateral oophorectomy.3,9 The present case was detected at fistulogram and laparotomy during work-up of a child with vestibular discharge. Wharton reported that in 3 out of 4 cases of supernumerary ovary and in about one-fourth of accessory ovary, additional defects
6
ACCEPTED MANUSCRIPT
including congenital renal and gynecological abnormalities may be found.1 Our patient had horseshoe kidney along with vertebral defects. Printz et al discussed the embryology of supernumerary ovaries in detail.6 Briefly,
RI PT
ovaries develop from the germinal ridge (giving rise to all cells except oogonial cells) and the caudal-dorsal yolk sac endoderm (providing the gonocytes which become oogonia and gonocytes). Since the gonocytes develop a site distant from germinal
SC
ridge, they migrate through the dorsal mesentery (which later becomes greater omentum) to invade the germinal ridge. Hence, it is assumed that migratory arrest of
M AN U
one or more gonocytes within the dorsal mesentery may give rise to dermoid cyst in greater omentum. Alternatively, germinal ridge transplant, i.e. detachment and physical transplant of the cranial part of germinal ridge after incorporation of gonocyte, to the dorsal mesentery has also been proposed as a mechanism of ovarian ectopia. Of these
TE D
two proposed mechanisms, germinal ridge transplant is more likely in the present case, since the ectopic structure contained normal ovary apart from teratoma, signifying origin from germinal ridge.
EP
A variety of tumors have been reported to develop in an ectopic ovary, including dermoid cyst, serous and mucinous cystadenomas and cystadenocarcinomas and
AC C
mature cystic teratomas.4,7,8 In the present case, the child had mature teratoma occurring in a supernumerary ovary. In conclusion, the present case emphasizes the rarity of supernumerary ovary in a child. Also, pediatric surgeons, radiologists and pathologists should be aware of this phenomenon so as to be able to evaluate a case of ovarian tumor at an extragonadal site for the possibility of occurrence in an undetected supernumerary ovary. 7
ACCEPTED MANUSCRIPT
References 1. Wharton LR: Two cases of supernumerary ovary and one accessory ovary, with an analysis of previously reported cases. Am J Obstet Gynecol 1959; 78:1101.
RI PT
2. Lachman MF, Bermann MM: The ectopic ovary: a case report and review of the literature. Arch Pathol Lab Med 1991; 115:233.
3. Pearl M, Plotz EJ: Supernumerary ovary: report of a case. Obstet Gynecol 1963;
SC
21:253.
4. Hogan ML, Barber OD, Kaufman RH: Dermoid cyst in supernumerary ovary of the
M AN U
greater omentum: report of a case. Obstet Gynecol 1967; 29:405.
5. Kini H, Baliga PB, Pai KG: Supernumerary ovary associated with Wilms' tumor. Pediatr Surg Int 1998; 13:67.
6. Printz JL, Choate JW, Townes PL, Harper RC: The Embryology of supernumerary
TE D
ovaries. Obstet Gynecol 1973; 41:246.
7. Barik S, Dhaliwal LK, Gopalan S, Rajwanshi A: Adenocarcinoma of the supernumerary ovary. Int J Gynaecol Obs 1991; 34:75.
EP
8. Sonntag B, Lellé RJ, Steinhard J, Brinkmann OA, Hungermann D, Kiesel L: Retroperitoneal mucinous adenocarcinoma occurring during pregnancy in a
AC C
supernumerary ovary. J Obstet Gynaecol 2005; 25:515. 9. Kosasa TS, Griffith CT, Shane JM, Leventhal JM, Naftolin F: Diagnosis of a supernumerary ovary with human chorionic gonadotrophin. Obstet Gynecol 1976; 47:236.
8
ACCEPTED MANUSCRIPT
Legends Figure 1 Coronal (A) and sagittal (B&C) images reveal a long tubular sinus tract (thick white arrow in A&B) leading into a retroperitoneal soft tissue mass with intralesional fat
RI PT
(B, thin small white arrow) and bony component (C, thin long white arrow).
Figure 2 Axial images (A & B) revealing a retroperitoneal mass with intralesional fat (small white arrow). Associated horse-shoe kidney (B) is also noted.
SC
Figure 3 Histological photomicrographs showing ovarian tissue with primordial follicles in the cyst wall (A, H&E x100). Sections from the mass demonstrating skin with
M AN U
appendages (B, H&E x100), cartilage and bone (c, H&E x100) and marrow tissue (D,
AC C
EP
TE D
H&E x100).
9
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S1083-3188(15)00265-X
DOI:
10.1016/j.jpag.2015.07.005
Reference:
PEDADO 1878
To appear in:
Journal of Pediatric and Adolescent Gynecology
Received Date: 22 January 2015 Revised Date:
29 July 2015
Accepted Date: 29 July 2015
Please cite this article as: Gupta R, Verma S, Bansal K, Jain V, Sengar M, Mohta A, Mature teratoma in a supernumerary ovary in a child: report of the first case, Journal of Pediatric and Adolescent Gynecology (2015), doi: 10.1016/j.jpag.2015.07.005. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Title: Mature teratoma in a supernumerary ovary in a child: report of the first case Authors: Ruchika Gupta, M.D.*1, Sarika Verma D.N.B.**1, Kalpana Bansal, M.D.*2, Vishesh Jain,
*Assistant Professor, **Senior Resident, ***Professor
RI PT
M.S., M.Ch.*3, Mamta Sengar, M.S., M.Ch.*3, Anup Mohta, M.S., M.Ch.***3
Departments of 1Pathology, 2Radiodiagnosis and 3Pediatric Surgery
SC
Chacha Nehru Bal Chikitsalaya
Delhi – 110031, India
Address for Correspondence: Dr. Ruchika Gupta
TE D
Assistant Professor & HOD
M AN U
Geeta Colony
Department of Pathology
Chacha Nehru Bal Chikitsalaya
India
AC C
Delhi – 110031
EP
Geeta Colony
Ph: +91-9643308237
E-mail: [email protected] Source of financial support: None
1
ACCEPTED MANUSCRIPT
ABSTRACT Background: Supernumerary ovary, i.e. ovarian ectopia having no anatomic connection with the normally placed ovaries, is a rare gynecologic condition. To the best
RI PT
of our knowledge, only one pediatric case of supernumerary ovary has been reported to date in the English literature.
Case: A four-year girl was assessed for foul-smelling vestibular discharge and found to
SC
have a fistulous tract with opening near the vaginal orifice. Fistuloscopy revealed hair in the lumen of the tract. Computed tomography scan showed a retroperitoneal mass in
retroperitoneal supernumerary ovary.
M AN U
continuation of the tract. Excision of the mass revealed a mature teratoma in a
Conclusion: Supernumerary ovary, a gynecologic rarity, is even more uncommon in children. Hence, a thorough clinic-radiological-pathological correlation is mandatory to
TE D
diagnose extragonadal ovarian tumors arising in supernumerary ovaries.
AC C
EP
Key Words: Supernumerary, Ovary, Mature teratoma, Retroperitoneum, Pediatric
2
ACCEPTED MANUSCRIPT
INTRODUCTION Supernumerary ovary is a gynecologic rarity, which needs to be differentiated from accessory ovary in that the former has no anatomical connection with the normally
RI PT
located ovaries.1 It has been suggested recently to include both supernumerary and accessory ovaries in the term ‘ectopic ovary’.2 An extensive review of the available indexed English literature revealed about 30 cases of supernumerary ovaries, mainly in
been reported so far in the available literature.5
SC
adults with a wide age range.3,4 Only one case of supernumerary ovary in a child has
M AN U
The embryology of supernumerary ovary has been discussed in detail by Printz et al, suggesting migratory arrest of gonocytes or germinal ridge transplant as the possible hypotheses leading to this phenomenon.6 Cases of surface epithelial tumors as well as germ cell tumors (teratoma) have been reported in supernumerary ovaries.4,7,8
TE D
This report describes the case of a young girl with mature teratoma arising in a supernumerary ovary and presenting as vestibular discharge. This is the second
AC C
EP
pediatric report of supernumerary ovary, to the best of our knowledge.
3
ACCEPTED MANUSCRIPT
CASE A four-year-old girl presented with foul-smelling vestibular discharge for the last two years. There were no associated urinary complaints or history of bloody discharge. No
RI PT
significant medical or surgical history was present. Local examination revealed a small opening in the vestibule on the left side of vaginal orifice. A fine feeding tube could be inserted in the opening for 2-3 cm inside. The anus was normal and no rectovestibular
SC
fistula was detected.
Fistulogram through the opening revealed a blind ending tract in the pelvis. The tract
M AN U
was not communicating with the rectum. An examination under anesthesia with endoscopy was planned. The opening did not allow no. 5 cystoscope. However, after dissection of the tract for 3 cm from perineal end, the tract widened and a no. 7 cystoscope was easily inserted in the tract. Endoscopy revealed presence of hair inside
TE D
the lumen. The dissected end of the tract was sutured to the perineum and a computed tomography scan (CT scan) performed.
Computed tomography (CT) scan revealed a contrast-opacified long tubular sinus tract
EP
extending intra-abdominally from right lateral vestibular opening to the D9 vertebral level leading into a well-defined lobulated retroperitoneal soft tissue mass with intralesional
AC C
fat and bony component (Fig. 1 and 2), the latter being connected to D9-D11 vertebral bodies which appeared fused (block vertebra). Alpha-fetoprotein levels (AFP) of the child were within normal range. The child was planned for exploratory laparotomy and excision of the tract and the mass. Intra-operatively, the tract was seen to extend superiorly in the midline ending in a mass lying just above the isthmus of a horseshoe
4
ACCEPTED MANUSCRIPT
kidney. A bony extension was seen from the mass to the vertebra and was divided flush with the vertebra. Bilateral normal ovaries were present in the pelvis. We received a specimen of irregular globular soft tissue mass measuring 4x3x2 cm with
RI PT
attached tubular structure, 10 cm long. The mass, on cut-section, was homogenous yellow-white with focal gritty areas and a small cyst, 1 cm in diameter.
The soft tissue was processed in entirety in multiple sections. Histologic sections from
SC
the cystic area showed normal ovarian parenchyma with primordial follicles (Fig. 3a). Sections from rest of the mass showed features of a mature teratoma composed of
M AN U
epidermis, skeletal muscle, cartilage, bony trabeculae and marrow tissue (Fig. 3b-d). Immature elements were not seen in any of the sections. A review of the CT findings by the radiologist confirmed the presence of eutopic ovaries in addition to this mass. Hence, a final pathologic diagnosis was mature teratoma arising in a supernumerary
TE D
ovary.
The postoperative period of the child was uneventful. The child has been recurrencefree in one year of follow-up. She is also being evaluated for vertebral anomalies and
AC C
EP
scoliosis by the orthopedic surgeon.
5
ACCEPTED MANUSCRIPT
SUMMARY & CONCLUSION Supernumerary ovary is a rare gynecologic condition and is usually detected incidentally. Differentiation needs to be made from 'accessory ovary', in which extra
RI PT
ovarian tissue is placed near the normally placed ovary and is usually connected to the normal ovary. On the other hand, supernumerary ovary, as described by Wharton in 1959, includes those rare cases of ectopia where the third ovary is entirely separate
SC
from normally located ovary and apparently arises from a separate primordium.1 Lachman has suggested that the term 'ectopic ovary' should replace the terms
M AN U
supernumerary and accessory ovary and be defined as any ovarian tissue additional to normal ovaries.2 An extensive review of the available indexed English literature revealed about 30 reported cases of supernumerary ovaries, primarily in adults. The age range of previously reported cases of supernumerary ovaries has been wide,
TE D
from 17 years through 80 years. Supernumerary ovaries are rare in children. An extensive review of the available indexed English literature revealed only one previously reported case of supernumerary ovary in a 5-year-old child.5 Our case is the second
EP
report of supernumerary ovary in a child and first pediatric report of mature teratoma in a supernumerary ovary. Most of the cases have been asymptomatic, detected on
AC C
autopsy or incidentally at laparotomy. Only in rare cases, supernumerary ovary was suspected pre-operatively, primarily due to menstrual bleeding after bilateral oophorectomy.3,9 The present case was detected at fistulogram and laparotomy during work-up of a child with vestibular discharge. Wharton reported that in 3 out of 4 cases of supernumerary ovary and in about one-fourth of accessory ovary, additional defects
6
ACCEPTED MANUSCRIPT
including congenital renal and gynecological abnormalities may be found.1 Our patient had horseshoe kidney along with vertebral defects. Printz et al discussed the embryology of supernumerary ovaries in detail.6 Briefly,
RI PT
ovaries develop from the germinal ridge (giving rise to all cells except oogonial cells) and the caudal-dorsal yolk sac endoderm (providing the gonocytes which become oogonia and gonocytes). Since the gonocytes develop a site distant from germinal
SC
ridge, they migrate through the dorsal mesentery (which later becomes greater omentum) to invade the germinal ridge. Hence, it is assumed that migratory arrest of
M AN U
one or more gonocytes within the dorsal mesentery may give rise to dermoid cyst in greater omentum. Alternatively, germinal ridge transplant, i.e. detachment and physical transplant of the cranial part of germinal ridge after incorporation of gonocyte, to the dorsal mesentery has also been proposed as a mechanism of ovarian ectopia. Of these
TE D
two proposed mechanisms, germinal ridge transplant is more likely in the present case, since the ectopic structure contained normal ovary apart from teratoma, signifying origin from germinal ridge.
EP
A variety of tumors have been reported to develop in an ectopic ovary, including dermoid cyst, serous and mucinous cystadenomas and cystadenocarcinomas and
AC C
mature cystic teratomas.4,7,8 In the present case, the child had mature teratoma occurring in a supernumerary ovary. In conclusion, the present case emphasizes the rarity of supernumerary ovary in a child. Also, pediatric surgeons, radiologists and pathologists should be aware of this phenomenon so as to be able to evaluate a case of ovarian tumor at an extragonadal site for the possibility of occurrence in an undetected supernumerary ovary. 7
ACCEPTED MANUSCRIPT
References 1. Wharton LR: Two cases of supernumerary ovary and one accessory ovary, with an analysis of previously reported cases. Am J Obstet Gynecol 1959; 78:1101.
RI PT
2. Lachman MF, Bermann MM: The ectopic ovary: a case report and review of the literature. Arch Pathol Lab Med 1991; 115:233.
3. Pearl M, Plotz EJ: Supernumerary ovary: report of a case. Obstet Gynecol 1963;
SC
21:253.
4. Hogan ML, Barber OD, Kaufman RH: Dermoid cyst in supernumerary ovary of the
M AN U
greater omentum: report of a case. Obstet Gynecol 1967; 29:405.
5. Kini H, Baliga PB, Pai KG: Supernumerary ovary associated with Wilms' tumor. Pediatr Surg Int 1998; 13:67.
6. Printz JL, Choate JW, Townes PL, Harper RC: The Embryology of supernumerary
TE D
ovaries. Obstet Gynecol 1973; 41:246.
7. Barik S, Dhaliwal LK, Gopalan S, Rajwanshi A: Adenocarcinoma of the supernumerary ovary. Int J Gynaecol Obs 1991; 34:75.
EP
8. Sonntag B, Lellé RJ, Steinhard J, Brinkmann OA, Hungermann D, Kiesel L: Retroperitoneal mucinous adenocarcinoma occurring during pregnancy in a
AC C
supernumerary ovary. J Obstet Gynaecol 2005; 25:515. 9. Kosasa TS, Griffith CT, Shane JM, Leventhal JM, Naftolin F: Diagnosis of a supernumerary ovary with human chorionic gonadotrophin. Obstet Gynecol 1976; 47:236.
8
ACCEPTED MANUSCRIPT
Legends Figure 1 Coronal (A) and sagittal (B&C) images reveal a long tubular sinus tract (thick white arrow in A&B) leading into a retroperitoneal soft tissue mass with intralesional fat
RI PT
(B, thin small white arrow) and bony component (C, thin long white arrow).
Figure 2 Axial images (A & B) revealing a retroperitoneal mass with intralesional fat (small white arrow). Associated horse-shoe kidney (B) is also noted.
SC
Figure 3 Histological photomicrographs showing ovarian tissue with primordial follicles in the cyst wall (A, H&E x100). Sections from the mass demonstrating skin with
M AN U
appendages (B, H&E x100), cartilage and bone (c, H&E x100) and marrow tissue (D,
AC C
EP
TE D
H&E x100).
9
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