Case 1

D. ASHLEY HILL
Washington University Medical Center
St. Louis, MO

Clinical Summary:

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 cyst.

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 desmin positive.

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).

Case 2

JOHN M. HICKS
Texas Children's Hospital and Baylor College of Medicine
Houston, TX

Clinical Summary:

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).

Case 3

CHERYL COFFIN
Primary Children's Medical Center
Salt Lake City, UT

Clinical Summary:

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 biopsy.

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.

Case 4

DAVID PARHAM
Arkansas Children's Hospital
Little Rock, AR

Clinical Summary:

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.