Case 4 -
Sertoli Cell Tumor of the Ovary
Louis P Dehner
St. Louis Children's Hospital, Washington
University Medical Center
St. Louis, MO
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The patient is a 5-year-old female who was seen in the emergency department with a 4-5 day history of
moderate to severe, cramping intermittent pain in the periumbilical region. There was regularity to the
pain especially over the prior two days. She had had several bouts of vomiting over the last 24 hours.
Physical examination revealed an afebrile child who did not appear to be in acute distress, was well
nourished and was normally developed without any signs of endocrine dysfunction. Thoracic and abdominal
scars were noted. The physical examination was otherwise unremarkable including a negative abdominal
A hemogram was performed with a hemoglobin of 12.1 g/dl and a white cell count of 16,500
with 85% segmented neutrophils. CT examination revealed a multicystic mass in the left kidney measuring
4.0 x 2.5 cm and a rounded soft tissue mass in the left pelvis immediately adjacent and anterior to the
rectum which measured 3.4 x 3.2 cm. This mass was questioned as possibly arising in the left ovary.
The pre-operative diagnosis was torsion of the left ovary. At the time of surgery, there
was torsion of the left ovary with an intensely hemorrhagic appearance to the ovary as well as the
presence of a 3-4 cm mass which was contiguous to the ovary.
The section is from the resected left ovary which was described as weighing 48 gm and a
lobulated, hemorrhagic mass measuring 8 x 4 x 2 cm.
Case 4 - Figure 1
Hemorrhagic external surface and hemorrhagic contents of the cystic left ovary also demonstrates bulging nodules as seen through the capsular surface.
Case 4 - Figure 2
Extensive areas of the left ovary have undergone hemorrhagic necrosis which is the typical pathology of torsion. In some cases, it may be difficult to appreciate any underlying additional pathology, but not in this specimen.
Case 4 - Figure 3
Though the nodules of tumor also displayed the presence of interstitial hemorrhage, there is sufficient preservation to appreciate both architectural and individual microscopic features. The multinodular character is appreciated in this low magnification view. There is variation in the histologic composition of this tumor from one area to another.
Case 4 - Figure 4
This microscopic field shows the presence of uniformly small tubules adjacent to the loosely textured spindle cell mesenchyme.
Case 4 - Figure 5
Other foci are composed of well formed tubules and poorly formed cord-like structures.
Case 4 - Figure 6
This microscopic field shows the presence of poorly formed cords of basophilic cells which blend into a fibroma-like stroma.
Case 4 - Figure 7
Cystic areas show the presence of papillary profiles whose papillae are lined by a similar population of basophilic cells seen elsewhere in the tubules.
Case 4 - Figure 8
Immunohistochemistry confirms the diagnosis of a sex-cord stromal tumor with a panel of stains including cytokeration.
Case 4 - Figure 9
Vimentin expression by the tumor cells is less intense than the cytokeratin in Figure 8.
Case 4 - Figure 10
Calretinin staining is focally positive in tumor cells. The immunophenotype of sex-cord stromal tumors has some overlap with surface epithelial tumors of the ovary and mesothelioma except for the expression of inhibin. These three tumor types have considerable overlap since they share a common embryogenesis.
Case 4 - Figure 11
Inhibin positivity is a useful marker in the differentiation of a sex-cord stromal tumor from a surface epithelial neoplasm of the ovary.
Case 4 - Figure 12
The tumor demonstrates strong and diffuse nuclear reactivity for WT-1.
The left ovary has a bosselated appearance from the capsular aspects. It measures 8 X 4 X
2 cm and weighs 48 gm. An attached fallopian tube is identified. A smooth, glistening, brownish-tan to
hemorrhagic capsular surface is noted, but it is also appreciated that a substantial portion of the ovary
is cystic and hemorrhagic from the external aspects. Bisection reveals the presence of three mural
nodules measuring from 2.2 to 3.5 cm in greatest dimension; these nodules have a brownish-red to tan
appearance. Overall, there is a hemorrhagic quality to the entire mass consistent with the clinical
impression of torsion.
Microscopically, the nodules are composed of a relatively uniform, densely packed small
tubules, cords, solid nests and cysts in a variably conspicuous edematous and hemorrhagic immature
appearing stroma. The individual tumor cells are uniformly basophilic due to the dense nuclear chromatin
and an inconspicuous rim of cytoplasm. Mitotic figures are sparing in number. Leydig cells are not
identified within the interstitum or cellular profiles. Some foci have a mixed pattern of tubular
structures associated with a spindle cell stroma having a resemblance to a cellular fibroma. Cystic
areas are limited in extent, but some of these foci are associated with papillary profiles. A loosely
cellular mesenchyme without obvious tumor has variably edematous appearance resembling massive edema of
the ovary. Extensive areas are hemorrhagic where the tumor had undergone hemorrhagic necrosis. The
tumor appears to be confined to the ovary and there is no evidence of capsular invasion or surface
Immunohistochemically, the tubular structures, cords and nests display uniform staining
for cytokeratin and less intense reactivity for vimentin. These same structures are positive for
inhibin, calretinin and the nuclei for WT-1.
It is almost one year following the most recent surgery and the patient is doing well
without evidence of recurrent or metastatic disease. The cystic lesions in the lung remain stable and
the cysts in the left kidney are likely residual cystic nephroma.
When this 5-year-old girl presented with acute abdominal pain and was discovered to have a
mass in the left lower quadrant-pelvis, the perioperative impression favored a torsion of the left ovary.
Though ovarian torsion in children is a relatively uncommon clinical event, it is estimated to be
responsible for an acute surgical abdomen in 3% of females in the first two decades of life. A review of
the experience of ovarian pathology resulting in an oophorectomy or cystectomy among 521 females between
the ages of 0 and 20 years from the St. Louis Children's Hospital (SLCH), revealed that torsion with
infarction of the ovary accounted for 11% of cases, exceeded only by mature teratomas (24% of cases) and
non-neoplastic cysts (23%). Approximately 5% of the mature teratomas presented with torsion, but most of
the torsion-infarctions did not have obvious underlying pathology which can be difficult to appreciate if
there is extensive hemorrhagic infarction. Among the 59 cases of torsion-infarction (SLCH), 46%
presented at or before one year of age, 20% between 2 and 11 years and 34% between 12 and 20 years.
Underlying pathology in a torsed ovary may be seen in less than 50% of cases whereas it is appreciably
higher in young adult to middle-aged women.
Another perspective on our case is the topic of ovarian neoplasms in childhood and
adolescence. Over the years, several series of ovarian tumors in this age group have appeared in the
literature with similar experiences which not surprisingly contrasts with that seen in adult women beyond
the age of 20 years where surface epithelial-mullerian tumors in the three pathologic categories of
benign, borderline and malignant are the most common. If one restricts the discussion to the 20-40 year
age group, the mature teratoma accounts for 65% to 70% of all primary ovarian neoplasms. Drawing upon
the SLCH experience, neoplasms were diagnosed pathologically in 64% of all resected ovaries. In keeping
with experience of others, germ cell neoplasms represented 51% of cases, surface epithelial-mullerian
tumors in 28% and sex-cord stromal tumors in 14%. The tumors and the age groups at diagnosis are
summarized in Table 1. Approximately 75% of all ovarian tumors are diagnosed between the ages of 12 and
20 years and 2% in infants one year old or less. Our patient is one of the 12 who were diagnosed with a
sex-cord stromal tumor in the 2-11 age group. Mature and immature teratomas constituted almost 50% of
ovarian tumors in the latter age group.
Sex-cord stromal tumors (SCST) in children and adolescents represent the smallest category
of primary ovarian neoplasms. In our series, the number of SCSTs is disproportionately larger when
compared to other series since several of these cases were seen in consultation. The case under
discussion is a patient who has been seen at the SLCH on several prior occasions to be discussed later.
A more representative figure for SCSTs in children is 5% or so of primary ovarian neoplasms. The
pathologic types of SCSTs from our series are summarized in Table 2 with almost 50% of cases diagnosed as
granulosa cell tumors with the juvenile type as the single most common type of SCST. The single largest
clinicopathologic series of 72 SCSTs in children is from the Kiel Pediatric Tumor Registry which reported
the juvenile granulosa cell tumor as constituting 65% of cases followed by the Sertoli Leydig cell tumor
(19% of cases). There were no examples of pure Sertoli cell tumors in the latter study.
Since pure Sertoli cell tumors are so uncommon and especially so in children, there is
some uncertainty about their clinical behavior except for the fact that this neoplasm has the potential
for malignant behavior like several of the other SCSTs. In terms of the morphology, these tumors are
recognized by the formation of tubulo-glandular and cystic structures which can mimic or suggest the
possibility of a neuroendocrine, endometrioid, germinomatous or alveolar soft part neoplasm. A poorly
differentiated or unclassified type of SCST may be considered in those cases with a more stromal
appearance and poorly formed tubules. Oliva and associates have reported on the clinicopathologic
features of 54 cases of ovarian Sertoli cell tumors which is seemingly the largest series of such cases.
The youngest patient in this study was a 2-year-old and 7 (13%) of 54 patients were "prepubertal" at the
time of diagnosis and six presented with isosexual pseudoprecocity. Most tumors had a solid, tan to
yellow lobulated appearance on cut surface, but nine cases were cystic and solid like our case. Tubules
with a resemblance to immature seminiferous tubules are arranged in lobular formations and represents the
most common microscopic feature. If there is stromal separating the lobules, Leydig cells, if present,
are found within a loose myxomatous mesenchyme to establish the tumor as a Sertoli Leydig cell tumor.
The immunohistochemical phenotype of the Sertoli cell tumor is similar in most respects to the other
SCSTs. These tumors are positive for vimentin, cytokeratin, CD99, calretinin and inhibin in 50% or more
of cases. WT-1 is also a useful marker as it was in our case. If one is considering a neuroendocrine
neoplasm, it should be noted that neuron specific enolase is expressed in about one-half of Sertoli cell
tumors, but chromogranin is uniformly negative.
Juvenile granulosa cell tumor, Sertoli-Leydig cell tumor and Sertoli cell tumor are neoplasms whose
prognosis are determined to a great extent by the pathologic stage as documented by Schneider and
associates in a pediatric population. Since the overwhelming majority of SCSTs in children are confined
to the ovary and completely resectable, the overall survival is 90% or greater in most cases. However,
extension beyond ovary into the pelvis is accompanied by a reduction of survival to 70% or less.
To this point in our discussion, this case would seem to have offered us several
pedagogical points on ovarian masses in childhood and the types of neoplasms presenting in the ovary of
children. However, there is one more lesson which this case serves up. In the pediatric pathology slide
seminar in 2004, Hill discussed the case of a five-month-old female who presented with fever and
respiratory symptoms to suggest the diagnosis of influenza. Imaging studies at that time revealed a cyst
in the left lower lobe which was thought to represent congenital cystic adenomatoid malformation. A
lobectomy was performed. On pathologic examination, the filmy, multicystic structure was a cystic
pleuropulmonary blastoma or type I PPB. Subsequent imaging studies revealed a cystic nephroma in the
left kidney and additional cystic lesions in the right lung which were excised and proved to be type I
PPBs. There was also a positive family history of childhood malignancies in the mother and a maternal
This patient is the same little girl and is now the fourth child that we have seen with a
previously diagnosed PPB who has developed an ovarian SCST, three Sertoli cell tumors and one Sertoli
Leydig cell tumor. Family members of other children with PPBs have been reported with SCSTs, one of
these the mother of a child with a PPB and SCST. Given the relative rarity of ovarian SCSTs in children,
it is thought that this association with PPB is more than simply chance. Our patient is undoubtedly the
proband in another family with the familial PPB predisposition syndrome (OMIM 601200). It is estimated
that approximately 40% of children with PPB have a family history to suggest the presence of the
syndrome. A summary of the various diseases associated with PPB has been recently compiled by Priest and
associates. This child qualified shortly after her initial presentation with the development of
multifocal PPBs and cystic nephroma. The latter is the most common extrapulmonary pathology found in
One final note relates to some of this specific syndromic settings of ovarian SCSTs which
are well documented including the sex-cord stromal tumor with annular tubules in Peutz-Jeghers syndrome,
fibromas in the basal cell nevus syndrome, juvenile granulosa cell tumor in Ollier disease and Maffuci
syndrome and Sertoli cell tumor in Peutz-Jeghers syndrome and we propose in the familial PPB tumor
TABLE 1. OVARIAN NEOPLASMS AND AGE GROUP PRESENTATION*
From the Lauren V. Ackerman Laboratory of Surgical Pathology, Barnes-Jewish and St. Louis Children's Hospital, Washington University Medical Center, St. Louis, MO.
|TUMOR TYPE ||1 YR OR LESS ||2-11 YRS ||12-20 YRS|
|Mature teratoma (124) ||1 ||21 ||102|
|Benign serous tumor (49) ||- ||7 ||42|
|Sex-cord stromal tumor (46) ||4 ||12 ||30|
|Immature teratoma (29) ||- ||12 ||17|
|Benign mucinous tumor (28) ||- ||1 ||27|
|Miscellaneous tumors (19) ||2 ||8 ||9|
|Borderline surface tumors (15) ||- ||- ||15|
|Dysgerminoma (7) ||- ||3 ||4|
|Malignant surface tumors (3) ||- ||1 ||2|
|Tumorlike conditions (3) ||- ||- ||3|
|Endodermal sinus tumors (2) ||- ||1 ||1|
| Total ||7(2%) ||66(20%) ||252(75%)|
TABLE 2. OVARIAN SEX-CORD STROMAL TUMORS (1989-2008)*
From the Lauren V. Ackerman Laboratory of Surgical Pathology, Barnes-Jewish and St. Louis Children's Hospital, Washington University Medical Center, St. Louis, MO.
|TUMOR TYPE ||N ||%|
|Granulosa cell tumor ||22||47|
|Juvenile ||15 (33)|| |
|Adult ||7 (15) || |
|Sertoli-Leydig cell tumor ||9 ||20|
|Thecoma - fibroma ||7 ||15|
|Sertoli cell tumor ||5 ||11|
|Sclerosing stromal tumor ||2 ||4|
|Unclassified type ||1 ||3|
| Total ||46 ||100|
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