Pediatric Tumor Diagnostic Challenges
Sunday, March 7, 2004 - 7:30 p.m.
DEBORAH H. PERRY
Clinical histories are printed below.
Click on the case numbers for text and references of each case.
Click on each slide thumbnail image for an enlarged view
D. ASHLEY HILL
Washington University Medical Center
St. Louis, MO
The patient presented to her pediatrician at five months of age with fever, tachypnea and labored
respiration. She was diagnosed with Influenza B and admitted to the hospital. She had been born at
term with an uneventful neonatal course. She had no significant illnesses prior to admission although
her mother stated that her breathing had not been "normal" for some time. Her family history was
notable for B-cell leukemia in the mother. A chest X-ray on admission showed hyperaeration of the
left lung. A CT scan was performed and showed a markedly emphysematous left upper lobe with
compressive atelectasis of the left lower lobe and mediastinal shift. There were multiple fine
septations in the hyperinflated lobe with no visible normal lung tissue. The radiographic
differential diagnosis included congenital cystic pulmonary airway malformation (formerly called
cystic adenomatoid malformation) and congenital lobar emphysema. The patient recovered from her upper
respiratory infection and returned approximately 3 weeks later for resection of the abnormal left
upper lobe. At surgery, the left upper lobe showed massive overinflation with attenuation of the
visceral pleura. The upper lobe was dissected off the lower lobe with ligation of upper lobe branches
of the pulmonary vascular structures and the left upper lobe bronchus. No other cystic abnormalities
involving the pleura, mediastinum or left lower lobe were noted.
Gross examination of the 11 x 7
x 1.3 cm left upper lobe showed a 6.5 cm diameter bulla in the apex. Sections showed a wall thickness
of 0.2 cm and multiple incomplete fibrous septae consistent with collapsed cysts ranging from 1.0 to
2.0 cm in diameter. There was approximately 1 cm3 of brown fluid within the bulla. The uninvolved
parenchyma showed atelectasis and consolidation. Microscopic sections showed a pleural-based cystic
lesion. The cyst walls were variably cellular and lined by either benign mesothelium or benign
epithelium. Sections of cyst walls showed focal condensations of primitive stellate, round and
spindle-shaped cells beneath the cyst lining cells imparting a cambium layer appearance. These cells
showed nuclear hyperchromatism, high nuclear-to-cytoplasmic ratios and were mitotically active. Loose
fibrovascular tissue containing spindle-shaped cells resembling fibroblasts predominated in the deeper
portions of the septae. Small nodules of primitive cartilage were also seen in the cyst walls
focally. The lesion did not involve the margins of excision. The pathologic diagnosis was made. A
full body CT scan and head MR showed no evidence of metastatic disease. However, a hypodense lesion
in the lower pole of the left kidney was noted. A renal ultrasound determined this to be a simple
The patient was then followed with serial chest X-rays and CTs. At 4 months post-surgery a
CT scan identified 3 parenchymal cysts in the remaining left lung ranging from 0.24 to 0.62 cm in
diameter, which in retrospect were there 1 month post-surgery, and 2 cysts in the left kidney. At 6
months post-surgery CT scans showed 4 distinct cystic lesions in the left lung ranging from 0.27 to
2.1 cm in diameter, and 2 distinct cystic lesions in the right lung measuring 0.24 and 0.57 cm. The
left kidney contained 3 distinct cysts measuring 1.9 cm in maximum dimension. The patient was taken
to the operating room where a left partial nephrectomy and wedge resections of the left lower lobe
lung cysts were performed.
Gross examination of the kidney showed a subcapsular multiloculated
cyst measuring 1 cm in maximum dimension. Microscopic examination of the kidney showed a multilocular
cyst lined by bland, flattened cuboidal epithelium. The cyst walls contained loosely arranged
primitive mesenchymal cells with a stellate configuration in a myxoid background. No cambium layer
was seen. Within the parenchyma adjacent to the cysts, rare abortive glomeruli and dilated, irregular
tubules were seen similar to that seen in embryologic renal dysplasia. No blastema or cartilage was
present. Grossly, the wedge biopsies of lung showed subpleural, thin-walled multiloculated cysts
measuring 1.2 and 1.5 cm in greatest dimension. Microscopically the cysts had a similar architecture
to the previous left upper lobe specimen. There were subepithelial condensations of spindle cells
showing rare mitotic activity. No cartilage was present. Focally, the subepithelial spindle cells
contained abundant pink cytoplasm suggestive of rhabdomyoblastic differentiation. These cells were
The patient was started on Vincristine, Actinomycin D, Cyclophosphamide
alternating with Carboplatin, Etoposide and Ifosfamide following her second surgery. She is currently
well with no evidence of disease 9 months after her original diagnosis.
Case 1 - Figure 1 - Lung, Left upper lobe. The resected left upper lobe shows a 6.5 cm diameter thin-walled bulla in the apex. Incomplete fibrous septae traverse the bulla (long arrow). Consolidated lung parenchyma is visible at one aspect (short arrow).
Case 1 - Figure 2 - Lung, Left upper lobe. Sections show the cystic structures are pleural-based (upper panel). The bulla consisted of collapsed cyst walls with variable cellularity (lower panel). (H&E, original magnification x100 (upper panel); x 200 (lower panel)).
Case 1 - Figure 3 - Lung, Left upper lobe. Sections of cyst walls show focal condensations of primitive stellate, round and spindle-shaped cells beneath the benign cyst lining. A small nodule of primitive cartilage is developing out of the mesenchymal cells (arrow). (H&E, original magnification x 400).
Case 1 - Figure 4 - Lung, Left upper lobe. More developed cartilage nodules are shown here. The cartilage appears to arise from the spindled mesenchymal cells beneath the epithelium in a pattern reminiscent of mesenchymal chondrosarcoma. (H&E, original magnification x 400).
Case 1 - Figure 5 - Left kidney. The renal lesion is composed of bland cyst walls lined by flattened cuboidal cells with primitive stellate cells in a loose, myxoid stroma within the cyst wall. No cambium layer, atypical cells, blastema or cartilage is seen. (H&E, original magnification x 200; inset x 400).
Case 1 - Figure 6 - Lung, Left lower lobe. Cysts from the left lower lobe showed similar features to the upper lobe with small nodules of primitive cells within the cyst walls. Mitotic activity was seen focally. (H&E, original magnification x200; inset x 400).
Case 1 - Figure 7 - Lung, Left lower lobe. Focally the primitive cells contained abundant pink cytoplasm consistent with rhabdomyoblasts. A desmin immunohistochemical stain confirms the skeletal muscle differentiation. (H&E upper panel and lower left, original magnification x 200 and x400; Anti-desmin immunostain lower right, original magnification x 200).
JOHN M. HICKS
Texas Children's Hospital and Baylor College of Medicine
A 17-year-old Caucasian male presented to his local primary care physician with a complaint of right
thigh pain that had recently increased in intensity. The pain was deep seated and would awaken him
from his sleep. He had been using over the counter nonsteroidal anti-inflammatory medications to
lessen the pain. He also expressed concern about a tender mass that he had first noticed about 6
months previously. It had recently increased in size. With further questioning by the primary care
physician, the adolescent related that the onset of the discomfort began about 2 years ago following a
knee sprain during a high school football game. Treatment had not been sought for this injury.
Physical examination revealed a deep-seated firm right distal thigh mass that was tender to palpation
and was not freely moveable. The soft tissue overlying the mass had increased warmth. The mass was
believed to be contiguous with the underlying distal femur. The knee joint had a normal range of
motion and was without excessive anterior-posterior or medial-lateral mobility. Diagnostic imaging
studies found an eccentric mass arising within the right distal femur that appeared to have its
epicenter within the metaphysis and crossed the epiphyseal plate. The mass was predominantly
radiolucent with occasional areas of calcification. Sclerotic borders were not seen. The lesion
expanded the cortex of the bone and gave the impression of soft tissue extension. The cortex was
believed to be intact. The patient underwent a diagnostic biopsy of the mass by a local surgeon.
Multiple portions of red-tan to white-blue tissue, that measured 1.6 x 0.9 x 0.6 cm in aggregate, were
received by the local pathologist. Upon sectioning the tissue, it was noted that some portions of the
tissue had a glistening surface, while others had a gritty texture. Following evaluation by the local
pathologist, the case was sent for consultation. The adolescent was referred to an orthopedic
surgeon. Based upon the histopathologic findings (Figures 1-3) and inconsistency with the diagnostic
imaging results, additional tissue was obtained from the mass for further evaluation (Figures 4-7).
Based upon the histopathologic findings (Figures 1-3 are from glass slide 2A, the first biopsy) and
inconsistency with the diagnostic imaging results, additional tissue was obtained from the mass for
further evaluation (Figures 4-7, from glass slide 2B, the second biopsy).
Case 2 - Figure 1 - First biopsy of right thigh mass. The tumor is organized into a lobular architecture with a more cellular periphery and a less cellular center. The center has relatively abundant myxoid to chondroid matrix without a hyaline cartilage appearance.
Case 2 - Figure 2 - First biopsy of the right thigh mass: The tissue within the periphery of a lobule is comprised of spindled cells, rare osteoclast-like giant cells and also contains a vascular network separating the adjacent lobules.
Case 2 - Figure 3 - First biopsy of the right thigh mass: The center of a lobule is comprised of spindle to stellate cells with eosinophilic to amphophilic cytoplasm. These cells are embedded in a myxoid matrix. Mitotic activity is rarely seen.
Case 2 - Figure 4 - Second biopsy of right thigh mass: Multiple portions of tissue were received and varied from white glistening to red-brown tissue with focal areas with a gritty consistency on cut sections.
Case 2 - Figure 5 - Second biopsy of right thigh mass: This biopsy has a markedly different appearance compared with the first biopsy. The tumor is composed of markedly pleomorphic cells with a high nuclear to cytoplasmic ratio. The cells are embedded in a hyaline cartilage matrix and lie within lacunae.
Case 2 - Figure 6 - Second biopsy of right thigh mass: There are areas with noncalcified osteoid production by the chondroblastic tumor cells.
Case 2 - Figure 7 - Second biopsy of right thigh mass: Mitotic activity is readily seen within cellular areas of the tumor embedded in an eosinophilic myxoid matrix. These areas of the tumor were comprised of spindled to fusiform tumor cells that also formed osteoid matrix (not shown in this image).
Primary Children's Medical Center
Salt Lake City, UT
A 7-month old female presented with a mass on the jaw and a history of thrombocytopenia and anemia. A
previous tracheostomy had been performed for airway obstruction by a vascular mass, but no tissue was
obtained for pathologic evaluation. Systemic steroids, interferon, and embolization had failed to
stop the growth or diminish the size of the mass. An MRI scan demonstrated an enlarging heterogenous
mass involving soft tissue of the right neck and retropharyngeal space without skull or intercranial
involvement. Following the MRI scan, weekly vincristine, intermittent interferon, and occasional
intralesional steroids were given. A biopsy was performed two months later. The slides are from the
Case 3 - Figure 1 - Nodules of cellular vascular tissue are interspersed between bands of fibrous tissue, with occasional irregular empty dilated vessels resembling lymphatic vessels and congested capillary spaces.
Case 3 - Figure 2 - A cellular proliferation of spindled and polygonal cells is present with abundant small blood vessels.
Case 3 - Figure 3 - Spindled and plump polygonal cells form bundles and fascicles and are interspersed with blood vessels.
Case 3 - Figure 4 - Spindled and polygonal cells form a cellular mass with focal accumulation of hemosiderin. The endothelial cells have large vesicular nuclei with small nucleoli and occasional mitotic figures.
Arkansas Children's Hospital
Little Rock, AR
A seven year-old girl noted increasing pain and discomfort in her left ankle. A radiograph revealed a
well-defined, cystic lesion of the talus.
Case 4 - Figure 1 - A fibro-osseous lesion contains abundant, refractile, cementum-like bodies ("cementicles") enmeshed within a bland, fibroblastic stroma.
Case 4 - Figure 2 - Osteoblasts rim a bony spicule within the fibro-osseous lesion.