Musculoskeletal Pathology

·         Osteopetrosis (marble bone disease) is a rare inherited disease characterized by abnormal osteoclasts that histologically lack the usual ruffled borders and show decreased functioning. This abnormality results in reduced bone resorption and abnormally thickened bone. Long bones are widened in the metaphysis and diaphysis and have a characteristic “Erlenmeyer flask” appearance.

·         Osteosarcoma: malignant anaplastic cells, which are malignant osteoblasts that secrete osteoid. There may be marked variation histologically depending on the amount of type I collagen, osteoid, and spicules of woven bone produced.

aneurysmal bone cysts are composed of multiple blood filled spaces that are not lined by endothelial cells

Fibrous dysplasia displays a haphazard arrangement of immature bony trabeculae forming “Chinese letters,”

benign chondromas display lobules of hyaline cartilage with few cells. X-rays reveal a characteristic “O-ring sign” (radiolucent central cartilage surrounded by a thin layer of bone.

osteopetrosis is characterized clinically by thick bone trabeculae with osteoclasts that lack a normal ruffled border.

chondroblastomas are characterized by the presence of sheets of chondroblasts within a background of “chickenwire” mineralization and occasional non-neoplastic osteoclast-type giant cells.

·         OOs are characteristically painful because of the excess production of prostaglandin E2. The pain occurs at night and is promptly relieved by aspirin. X-rays typically reveal a radiolucent area (the tumor itself) surrounded by thickened (reactive) bone.

·         Histologically, Ewing’s Sarcoma is composed of a diffuse proliferation of small, uniform, round cells. Occasionally the tumor cells form rosettes around central blood vessels (Homer-Wright pseudorosettes), indicating neural differentiation. These small round “blue” cells are similar in appearance to the neoplastic cells of lymphoma, rhabdomyosarcoma, neuroblastoma and small cell (oat cell) carcinoma. To differentiate this lesion from these other malignancies, PAS staining of glycogen-positive, diastase-sensitive cytoplasmic granules within the tumor cells of Ewing’s sarcoma is characteristic. Also useful in differentiation from neuroblastoma is the fact that Ewing’s sarcoma is associated with the translocation t(11;22). This results in fusion of the EWS gene on chromosome 22 to a member of the ETS family of transcription factors, most commonly FLT1. That is, the most common result of the t(11;22) is the formation of the fusion gene EWS-FLI1.

·         Most cases of SMA have deletions of the survival motor neuron gene (SMN1) and the nearby neuronal apoptosis inhibitory protein gene (NAIP). The most common form of SMA is Werdnig-Hoffman disease (type I spinal muscular atrophy). Degeneration of the anterior horn (motor) neurons produces severe flaccid paralysis and hypotonia. Histologic examination of a muscle biopsy from a patient with Werdnig-Hoffman disease will reveal the combination of large numbers of small atrophic muscle fibers (panfasicular atrophy) along with scattered enlarged muscle fibers and fiber type grouping. The prognosis for a child with Werdnig-Hoffman disease is poor. The disease begins in the first couple of months of life and progresses to death by the age of 3.

·         The peripheral myelin protein 22 (PMP22) gene and the myelin protein zero (MPZ) gene are both associated with hereditary motor sensory neuropathy type I (Charcot-Marie-Tooth disease), while the ryanodine receptor 1 gene (RYR1) and the sodium channel 4A gene (SCN4A) are two of the many different genes involved in the pathogenesis of malignant hyperthermia, a rare clinical syndrome that is triggered by induction of anesthesia. The sodium channel 4A gene is also abnormal in patients with hyperkalemic periodic paralysis.

·         Histologically, examination of muscles from patients with dermatomyositis reveals perivascular inflammation within the tissue around muscle fascicles. This is in contrast to the other types of inflammatory myopathies, where the inflammation is within the muscle fascicles (endomysial inflammation). In particular, inclusion-body myositis is characterized by basophilic granular inclusions around vacuoles (“rimmed” vacuoles).

·         The most common type of malignant melanoma is superficial spreading melanoma, which is characterized by its lateral (radial) growth and upward infiltration of malignant cells within the epidermis, having a “buckshot” appearance (Pagetoid cells).

·         Two tumors that arise from fibroblasts in the dermis of the skin are the benign fibrous histiocytoma and the malignant dermatofibrosarcoma protuberans (DFSP). Benign fibrous histiocytomas are composed of a mixture of fibroblasts, histiocytes (some of which are lipid-laden), mesenchymal cells, and capillaries. Depending on which element predominates, these lesions have also been called dermatofibromas (mainly fibroblasts), fibroxanthomas (mainly histiocytes), and sclerosing hemangiomas (mainly blood vessels). Hyperplasia of the epidermis overlying a dermatofibroma is quite characteristic. In contrast, the lesions of dermatofibrosarcoma protuberans are cellular lesions composed of fibroblasts that form a characteristic pinwheel (storiform) pattern. They have irregular, infiltrative margins and are locally aggressive. They frequently extend into the underlying fat and complete excision is difficult. The overlying epidermis is characteristically thinned