Pathologic Quiz Case

Ovarian Mass in a 2-Year-Old Girl Presenting With Pleural Effusions

Christof Senger, MD; Leslie Diaz, MD; Howard Katzenstein, MD; Pauline M. Chou, MD

2-year-old girl presented to her primary physician

with increasing fatigue and decreasing appetite during a 10-day period, and an abdominal mass was palpated. Computed tomographic scan (Figure 1) performed at
the referring institution revealed a large retroperitoneal
tumor with prominent pelvic, abdominal, and mediastinal
masses associated with significant bilateral pleural effusions (right greater than left). Bone scan and skeletal surveys were negative for metastatic tumor. A 7-year-old
brother had a history of congenital heart disease (ventricular septal defect) and omphalocele. Additional family
history was remarkable for breast and pancreatic cancer.
The presumptive diagnosis was disseminated neuroblastoma. The patient was transferred to our institution for
further management. She was found to be in moderate
respiratory distress, and a right-sided thoracentesis was
performed for both therapeutic and diagnostic purposes.
Cytologic examination of the pleural fluid initially revealed a nonspecific malignant process, and the patient
subsequently underwent surgical exploration to obtain additional diagnostic material. Further workup of the cytologic specimen was performed concurrently.

Accepted for publication December 19, 2001.

From the Departments of Pathology (Drs Senger, Diaz, and Chou)
and Hematology and Oncology (Dr Katzenstein), Childrens Memorial
Hospital, Chicago, Ill. Dr Senger is currently with The Hospital for Sick
Children, Toronto, Ontario. Dr Diaz is currently with the University of
Texas M. D. Anderson Cancer Center, Houston, Tex.
Corresponding author: Pauline M. Chou, MD, Department of Pathology, Box 17, Childrens Memorial Hospital, Chicago, IL 60614 (email: pmchou@northeastern.edu).

e56 Arch Pathol Lab MedVol 127, January 2003

The tumor was observed intraoperatively as a mass emanating from the right ovary and essentially replacing the
normal ovarian tissue. There was diffuse nodal disease
and peritoneal implants as a result of transcelomic dissemination, which were not appreciated radiographically.
Intraoperative frozen section did not demonstrate histologic features suggestive of an epithelial or germ cell origin.
Incisional biopsy specimens from the ovary and peritoneal nodes confirmed the diagnosis subsequently rendered on the cytologic material alone, which was obtained
from the pleural effusions. A Papanicolaou-stained cytospin preparation revealed a highly cellular exudate composed of a mixture of cells (Figure 2). The background
consisted of clusters of reactive mesothelial cells (double
arrow) and lymphocytes (single arrowhead). There were
bizarre-appearing, discohesive giant cells, with pleomorphic hyperchromatic nuclei (single arrow) and a variable
amount of eosinophilic cytoplasm. Mitotic figures were
easily identified (double arrowhead). Not infrequently, tumor cells show very vacuolated cytoplasm (inset). Figure
3, A shows immunohistochemical stains for desmin, demonstrating cytoplasmic staining of paranuclear inclusionlike material. Figure 3, B shows an immunohistochemical
stain for myogenin, demonstrating nuclear positivity of
the tumor cells in a characteristic diffuse fashion. Figure
4 is a representative metaphase cytogenetic karyotype of
a tumor cell that has 94 chromosomes. A characteristic
translocation is highlighted by arrows. The presence of a
messenger RNA transcript was confirmed by reverse transcriptase polymerase chain reaction.
What is your diagnosis?

Pathologic Quiz CaseSenger et al

Arch Pathol Lab MedVol 127, January 2003

Pathologic Quiz CaseSenger et al e57

Pathologic Diagnosis: Alveolar Rhabdomyosarcoma,

Solid Variant
Rhabdomyosarcoma, particularly the alveolar subtype,
is one of the pediatric neoplasms that can present as a
disseminated tumor in the neonatal period or early childhood. It may be difficult, sometimes impossible, to determine the anatomic site from which the tumor originated.
It may be assumed that the origin is from the soft tissues.
Tumors other than rhabdomyosarcoma that can present
as disseminated masses in the pediatric age group include
the generalized form of infantile myofibromatosis, neuroblastoma, and hematopoietic neoplasms including lymphomas. More recently, it has been recognized that malignant rhabdoid tumor characterized by abnormalities of
chromosome 22q11, arising from soft tissues, may also
present in neonates as disseminated tumor.1
This case was unusual for several reasons. The patient
presented with pleural effusions as a result of mediastinal
involvement by tumor (primary mediastinal rhabdomyosarcomas not associated with a germ cell neoplasm have
been reported before).2 In our case, the primary tumor
most likely arose from the ovary and, notably, no associated germ cell component was identified. Moreover, peritoneal spread in a pseudomyxoma peritonei-like fashion
was present. This mode of spread is rather unusual and
expected in other neoplasms.
The frequency of intraperitoneal involvement of rhabdomyosarcomas at presentation is estimated to be about
7%.3 Other tumors that can show peritoneal involvement
in children include mesothelioma, desmoplastic small
round cell tumor, germ cell tumors (eg, gliomatosis peritonei), lymphoma, neuroblastoma, Wilms tumor, and intracranial tumors seeding via ventriculoperitoneal
shunts.3
Cytologic material from pleural, peritoneal, or pericardial fluids may be diagnostic in the pediatric population,
and positive specimens, as summarized from a comprehensive study,4 included lymphoma and leukemias (52%),
neuroblastoma (14%), Wilms tumor (9%), gonadal and extragonadal germ cell neoplasms (8%), bone and soft tissue
sarcomas (7%), epithelial neoplasms (5%), Ewing sarcoma
(2%), and other neoplasms (3%). Cytologic material from
pleural, peritoneal, or pericardial fluid may yield material
sufficient for a definitive diagnosis of rhabdomyosarcoma,
particularly when ancillary techniques are used. This is
well documented and includes, similar to our case, a report of a child presenting with massive pleural effusions.5
Because they are not infrequently seen in rhabdomyosarcomas with effusions, vacuolated cells in effusions sometimes confound the picture, since they are also suggestive
of a diagnosis of Burkitt lymphoma.
There are 4 histologic subtypes of rhabdomyosarcomas
described in children6: botryoid (accounting for 6% of all
tumors), spindle cell (3%), embryonal (49%), and alveolar
(31%). The corresponding 5-year survival rates were estimated at 95%, 88%, 66%, and 54%, respectively. Spindle
cell type and botryoid type are included in the overall
category of embryonal rhabdomyosarcoma. If alveolar features are present in any portion of the tumor, it is categorized as alveolar rhabdomyosarcoma. Tumors with
rhabdoid features are not classified as rhabdomyosarcomas. The spindle cell type is confined to the paratesticular
region. The botryoid type is defined as a tumor growing
into hollow visceral structures in a polypoid fashion, exe58 Arch Pathol Lab MedVol 127, January 2003

plaining its predilection for sites in the head and neck

region and the genitourinary tract. Embryonal rhabdomyosarcoma also favors the head and neck region. Alveolar rhabdomyosarcoma is most often found in the extremities or trunk.
The diagnoses of these tumors are typically established
on morphologic grounds and confirmed by immunohistochemical analysis (myogenin and desmin in combination are sufficiently specific). Embryonal rhabdomyosarcoma and alveolar rhabdomyosarcoma, solid subtype,
sometimes show similar morphologic structure, and distinction between them may be difficult. Younger children
are more likely to have embryonal tumors in the head and
neck or genitourinary tract, whereas alveolar tumors typically occur in the extremities of older patients. Fortunately, most tumors of the alveolar subtype display characteristic chromosomal changes, as seen in our case. There are
translocations involving the forkhead domain region on
chromosome 13, which encodes a transcription activator
in the forkhead domain region (FKHR). The most common
translocations involve members of the PAX gene family
(which are genes important as determinants of sequential
neural tube differentiation and segmentation during embryogenesis). The translocation t(2;13)(p36;q14), which
was previously identified in the solid variant,7 involves
the Pax3 gene on chromosome 2 and is found in more
than 60% of alveolar rhabdomyosarcomas. This was
true for our case, and Figure 4 is a karyogram with the
t(2;13)(p36;q14) highlighted by arrows. In our case, there
is also hyperdiploidy with an overall chromosome number of 94 and presence of numerous double minutes. A
total of 20 tumor cells were karyotyped, and the chromosome content ranged from 94 to 114 chromosomes.
The t(2;13) involving the Pax3 gene is more frequently
found in a group of patients who are older, have truncal
tumors, present with advanced stage, and typically have
an inferior prognosis.8 Another common translocation is
t(1;13)(p364) involving the PAX7 gene on chromosome
1,9 which is associated with a better prognosis.10 Currently,
it is unclear if DNA content has specific diagnostic or
prognostic implications and may be used as an independent predictor of survival.11 Ploidy may be correlated with
histologic subtype, and higher DNA contents are found in
the embryonal subtype. In general, hyperdiploidy (DNA
index 1.101.80) is found in patient groups with a better
clinical outcome compared with patient groups with either diploid or near-diploid or tetraploid or hypertetraploid tumors. The number of double minutes in our case
varied between 5 and 50. Double minutes in rhabdomyosarcomas may have negative prognostic implications. One
study identified multiple copies of the PAX7-FKHR fusion
gene on a subset of double minutes and multiple copies
of the MYCN gene on other double-minute chromosomes
in a rhabdomyosarcoma cell line.12
In conclusion, fluid cytologic material can be used to
arrive at a proper diagnosis in the setting of rhabdomyosarcoma. Moreover, the abundant number of malignant
cells that often present in these specimens can provide
material for additional complementary studies.
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rhabdoid tumor: a distinct clinicopathologic entity demonstrating abnormalities
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carcinomatous component. Hum Pathol. 1994;25:349356.

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