Martha Bennett Adams, MD

• Professor Emerita of Medicine

https://medicine.duke.edu/faculty/martha-bennett-adams-md

B hair loss youtube finasteride 5 mg on line, Higher magnification of B shows multinucleated giant cells and dialated stromal vessels hair loss in men vasectomy purchase finasteride 1mg visa. B hair loss guinea pigs buy finasteride 1 mg line, Higher magnification of A showing the so-called anoxic atypia affecting predominantly the mononuclear cells hair loss in men 70s pants discount 1mg finasteride mastercard. D hair loss cure purchase finasteride visa, Higher power view of C shows florid spindle-cell proliferation at the border of necrosis and viable tumor hair loss 4 months after pregnancy 5 mg finasteride amex. A, Low power view of an interface between necrosis on the left and viable tumor on the right. B, Higher power of A showing hyperchromasia of cells in the interface between necrosis and viable tumor. C, Interface between necrotic area and viable tumor showing a loose texture and nuclear hyperchromasia. A, Anteroposterior view of giant cell tumor in plain radiograph involving epiphysis of proximal tibial. B, Gross photograph of resection specimen shown in A with expansile red-brown tumor containing fine yellowish septations. The cortex overlying tumor is destroyed and expanded bone contour is delineated by thin fibrous capsule. C, High magnification showing two multinucleated giant cells within the mononuclear stroma. Note that the nuclei of mononuclear stromal cells and of multinucleated giant cells look similar. D, Histologic appearance of the same tumor showing scattered multinucleated giant cells within mononuclear stromal cells resembling histiocytes. E and F, Fine needle aspirates containing multiple mononuclear stromal cells and multinucleated osteoclastic cell. G, Higher power demonstrating mononuclear stromal cells with oval nuclei and discrete nucleoli. Inset, An oval histiocytic cell with two nuclei and densely eosinophilic cytoplasm. Treatment and Behavior Approximately 25% of conventional giant cell tumors are considered to be locally aggressive on clinical or radiologic grounds. Curettage supplemented by cryotherapy is used in some centers to reduce the rate of local recurrence. Wide excision with allograft or prosthetic replacement significantly reduces, but does not completely eliminate, recurrences and is performed when appropriate and technically feasible. Typically, it is a result of tumor implantation into soft tissue at the time of surgical treatment. In some unusual instances, it may occur many years after the removal of the primary tumor. In the past, radiation therapy was frequently used to control the disease locally and has been proved to be effective in preventing local recurrences. Because the majority of malignant transformations in giant cell tumor are linked to prior radiation, radiotherapy is no longer recommended as a primary mode of treatment. Typically the pulmonary nodules grow slowly and are amenable to surgical excision with a prospect for cure. A, Radiograph of knee of 17-yearold skeletally mature girl with a 6-month history of knee pain whose giant cell tumor involved lateral half of tibial plateau; subchondral bone was curetted and bone grafted. D, Histologic appearance of recurrent giant cell tumor is identical to primary neoplasm. A, Radiograph of knee of a 27-year-old woman shows eccentric lytic tumor on medial side of tibial plateau. B, Eighteen months later patient returned with palpable nodule in soft tissue beneath surgical scar (arrows) with peripheral calcification seen on radiograph. E, Photomicrograph of recurrent tumor nodule with peripheral shell of reactive bone. Development of sarcoma in conventional giant cell tumor is the most serious complication but fortunately is rare. As mentioned previously, the majority of secondary sarcomas that arise in association with conventional giant cell tumor are linked to prior radiation therapy. With the decline in the use of therapeutic irradiation for giant cell tumors, malignant transformation has become exceedingly rare. Special Techniques It appears that several cell types that belong to the macrophage/osteoclastic and osteoblastic lineages contribute to the development of giant cell tumors. Ultrastructurally, the cytoplasm of mononuclear cells contains abundant rough endoplasmic reticulum, moderate numbers of mitochondria, a few lysosome-like bodies, and occasionally multiple lipid vacuoles. In summary, the ultrastructure is of little help to elucidate various dilemmas related to the origin of a giant cell tumor. It suggests, however, that the mononuclear cells have some ultrastructural similarities with cells of histiocytic lineage, macrophage lineage, or both. In fact, some of the mononuclear cells express the receptor for the immunoglobulin G crystallizable fragment and differentiation antigens associated with a macrophagemonocyte lineage. The cells of monocytemacrophage lineage do not proliferate well in vivo and are usually eliminated from tissue culture explants. In summary, the main population of cells in giant cell tumor have phenotypic features of both macrophage-like and osteoclastic cells. Gly34Trp change in the majority of cases were found in approximately 90% of giant cell tumors. Little is known about the factors governing local aggressive behavior, recurrence rate, and metastatic potential of conventional giant cell tumors. This does not correlate with the clinical behavior of the lesion and cannot be used as a reliable factor for predicting recurrence or pulmonary metastases. Allelic losses of 1p, 9q, and 19q are frequent in giant cell tumors but do not correlate with local recurrence or metastatic potential. D, High proliferation rate documented by positive immunohistochemical staining for Ki67. The key to distinguishing these lesions is in the unswerving adherence to clinicoradiologic correlation to arrive at a diagnosis. Generally, a diagnosis of giant cell tumor is suggested by the presence of a radiolucent lesion in the end of a long bone or an equivalent epiphyseal site in a skeletally mature individual. Other common locations include the sacrum and "epiphyseoid" bones, such as the carpal and tarsal bones and the patella. The true giant cell tumor, for practical purposes, does not arise in the craniofacial skeleton, and it very rarely develops in nonepiphyseal locations. The short tubular bones of the hands and feet present a particular problem because of the morphologic overlap with giant cell reparative granuloma, which has a predilection for this skeletal site. In this situation, attention to the specific site of involvement with respect to epiphyseal location and skeletal maturity is particularly important. Perhaps the most important problem in histologic recognition of true giant cell tumor is created by the tendency for this tumor to undergo fibrohistiocytic reactive changes that can simulate benign or malignant primary tumors of fibrohistiocytic origin. Such changes can largely or even completely obscure the classic histologic appearance of giant cell tumor. It is this tendency that has led to the misapplication of the term benign or malignant fibrous histiocytoma of bone to some examples of altered giant cell tumor. Strict adherence to the use of clinicoradiologic correlation and thorough sampling of the tumor tissue avoid most of these errors in diagnosis. Another question that frequently arises is the extent to which the aggressiveness of a giant cell tumor can be predicted on the basis of histologic criteria. Whether to assign numeric grades or to use adjectival modifiers in designating local aggressiveness or metastasizing potential has been debated extensively. Our experience indicates that the use of such devices is without merit, except to designate giant cell tumor as conventional or malignant (either primary or secondary) on the basis of the presence or absence of frankly sarcomatous features. Conventional Giant Cell Tumor in Different Anatomic Sites the conventional giant cell tumor has identical microscopic features and biologic potential regardless of its anatomic location. However, in different anatomic sites and age groups, it may cause various diagnostic dilemmas. The clinical significance, the technical feasibility of complete removal, and consequently the chance for cure can also significantly differ in relation to the anatomic site. For this reason, it is necessary to provide separate descriptions of giant cell tumor and its differential diagnosis in various anatomic sites. Giant cell tumor occurs approximately 4 times more frequently in the lower extremities than in the upper extremities. Giant cell tumor occurs less commonly in the distal tibia, very rarely in the distal ulna and fibula, and very uncommonly around the elbow joint. When it occurs in the elbow joint, it is seen more frequently in the distal humerus and very rarely in the proximal ulna and the radius. In the epiphyses of the long tubular bones, a giant cell tumor has radiologic features of an eccentric epiphyseal or metaphyseal defect with well-defined margins and an expanded cortex that is very frequently, at least focally, destroyed. In a small percentage of cases, periosteal reaction can be present and is usually minimal. In thinner bones, such as the distal ulna or fibula, the lesion is usually centrally located with marked expansion of the bone contour. Although hemorrhage, necrosis, and a fibrohistiocytic xanthogranulomatous reaction can develop in any giant cell tumor, regardless of its location, such effects are seen much more frequently and are much more extensive in the weight-bearing bones of the lower extremities. In this location, it is common for the tumor to be nearly completely replaced by necrosis and secondary fibrohistiocytic xanthogranulomatous reaction. In the long tubular bones, giant cell tumor should be differentiated radiologically from chondroblastoma, nonossifying fibroma, chondromyxoid fibroma, aneurysmal bone cyst, pigmented villonodular synovitis, and osteogenic sarcoma. Occasionally, fibroblastic tumors, such as desmoplastic fibroma, fibrosarcoma, and malignant fibrous histiocytoma, may enter into the differential diagnosis. Chondroblastoma occurs in children and adolescents who have open epiphyses and typically has radiologically detectable calcifications. Chondroblastomas at the ends of long bone seldom cause expansion of the contour unless they contain secondary aneurysmal bone cysts, and cortical disruption is usually not present. Nonossifying fibroma is radiologically an eccentric metaphysealdiaphyseal lesion with well-developed scalloped sclerotic margins in skeletally immature patients. A, Radiograph of distal end of radius with disruption of cortex by expansile giant cell tumor. Chondromyxoid fibroma is an eccentric metaphyseal lesion with scalloped margins, fine trabeculations, and intact cortex. Its histologic features are so characteristic that only in the most unusual circumstances can it be confused with a giant cell tumor. De novo aneurysmal bone cysts produce lytic, eccentrically expansile defects in long bones that are easily distinguished from giant cell tumors by their predilection for the diaphysis or metaphysis. Conversely, it is usual for secondary aneurysmal bone cysts to occur in association with giant cell tumors of long bones. This combination usually alters the radiologic appearance by accentuating the expansile and destructive features of the giant cell tumor. For this reason, aneurysmal bone cysts that occur in the ends of long bones of adults should always raise the possibility of an underlying giant cell tumor. Pigmented villonodular synovitis of major joints sometimes invades the ends of long bones and produces lytic defects that can superficially resemble a giant cell tumor. This mimicry is complicated by the presence of many giant cells in the histologic sample of such lesions, but the clinical and radiologic evidence of bone defects in more than one bone bordering a joint can obviate this diagnostic problem. High-grade osteogenic sarcomas may occasionally produce osteolytic defects that mimic giant cell tumor. Fibroblastic tumors, such as desmoplastic fibroma, fibrosarcoma, and malignant fibrous histiocytoma, can radiologically mimic giant cell tumor. However, they are typically diaphyseal in location and show massive destruction of bone and cortex. Their histologic features are usually diagnostic, but occasionally it is difficult to distinguish a de novo malignant fibrous histiocytoma from secondary malignant change in an underlying giant cell tumor. In such instances, the clinical history, radiographs, and careful sampling of the tumor are very helpful. Approximately 3% to 4% of all giant cell tumors are found in the small bones of the hands and feet. Giant cell tumors in younger patients appear to occur in these locations more frequently than lesions in the long bones. In the small bones, it is unusual to see the eccentric epiphyseal origin unless the lesion is detected very early. Involvement of the epiphysis is almost a rule, although in small bones a significant portion of the shaft or even the entire bone can be involved. A giant cell tumor of the acral skeleton may show somewhat more aggressive behavior than one in the long tubular bones. A giant cell tumor of small tubular bones should be differentiated mainly from a giant cell reparative granuloma. If this diagnostic dilemma occurs, radiologic evidence of involvement of the epiphysis in a skeletally mature patient should favor the diagnosis of a giant cell tumor. On the contrary, lack of epiphyseal involvement and the presence of unfused epiphyseal plates should be considered as radiologic features in favor of a giant cell reparative granuloma. Enchondroma is seldom confused with giant cell tumor because of its location in the shaft and its characteristic calcification pattern. Pigmented villonodular synovitis arising in tendon sheaths of the hands and feet can erode short tubular bones and thus simulate giant cell tumors. Giant cell tumor of the vertebral column exclusive of the sacrum is extremely rare. Patients with giant cell tumors of the vertebral column have a tendency to be younger than patients with lesions of long tubular bones. When giant cell tumor affects a vertebral body, it usually occurs in a skeletally immature patient.

A hair loss cure google order 5 mg finasteride with visa, Computed tomogram of pelvis and sacrum of 60-year-old man with sclerosing variant of cystic angiomatosis hair loss eyebrows 5 mg finasteride free shipping. B hair loss nexplanon cheap 5 mg finasteride with amex, Radionuclide bone scan shows increased uptake in portions of pelvis showing sclerotic lesions in A and in left second and fifth ribs hair loss blog purchase generic finasteride. A hair loss in men zip wallet purchase generic finasteride canada, Sclerotic variant of cystic angiomatosis involving both left and right pelvic bones hair loss cure quotes cheap finasteride 1 mg with amex. B, Sclerotic lesions mimicking osteoblastic metastases adjacent to sacroiliac joint and iliac crest. Note multifocal sclerotic lesions mimicking osteoblastic metastasis adjacent to sacroiliac joints. A, Low power photomicrograph shows dilated, thin-walled vessels in marrow spaces of cancellous bone with delicate trabeculae of reactive woven bone surrounding angiomatosis elements. The active lesions are purely vascular, and the osteoclastic resorptive activity can be seen near the advancing edge. Stabilization of the lesion is associated with an increased amount of intervening connective tissue. In some cases, extensive involvement of the chest wall (ribs) is associated with pleural effusion and severe pulmonary compromise, which can lead to a fatal outcome. Because the clinical course of massive osteolysis is variable and unpredictable, the choice of a particular method of therapy is fraught with uncertainty. In fact, any histologically benign angiomatosis of bone or soft tissue may occasionally behave clinically as a slowly progressive disorder that eventually compromises the function of the affected organ. In such instances, major resection procedures including amputation may be required in order to control the process. Surgical resection, embolization, radiation therapy, steroids, and more recently, interferon alfa have all been used in cases showing progression. They are classified similarly to vascular neoplasms as of arterial, venous, or capillary in nature. They are predominantly soft tissue lesions and their involvement of the skeleton is rather secondary. These conditions are best diagnosed in correlation with clinical presentation and radiographic imaging data. Glomus Tumor the glomus body is a form of arteriovenous anastomosis that plays a role in thermal regulation. It is distributed throughout the body in the reticular dermis but is most frequently seen in the subungual region. The normal glomus body consists of an afferent arteriole that branches into two to four connecting arterioles. The arterioles have thick segments surrounded by concentric layers of modified perivascular smooth muscle cells. These segments are called Sucquet-Hoyer canals and consist of 932 13 Vascular Lesions single most common site is the subungual region of the fingers. They also can occur in the tip of the coccyx, where they arise from the glomus coccygeum. Exceptional cases of glomus tumor arising in other bones such as the proximal phalanx, tibia, ulna, and pelvis have also been reported. Clinical Symptoms Glomus tumors are extremely painful, and symptoms are often out of proportion with the size of the tumor. Paroxysms of pain in the affected area can be triggered by changes of temperature or even by minor mechanical disturbance of the affected area. Intraosseous lesions that cause these symptoms raise clinical suspicion of osteoid osteoma. In contrast to osteoid osteoma, pain from a glomus tumor is not predominantly nocturnal, has a paroxysmal pattern, and does not respond to salicylates. In addition to osteoid osteoma, intraosseous epidermal inclusion cysts and invasive subungual keratoacanthomas of the nail bed can produce lucent, painful lesions in the distal phalanx that must be distinguished from intraosseous glomus tumor. The lesions in bones other than phalanges are intracortical, expand the cortex, and promote mild sclerosis in the adjacent bone. In summary, together with its clinical symptoms, the lesion resembles osteoid osteoma on radiographs. In one of our cases the tumor eroded the cortex of the ulna and extended into the surrounding soft tissues. Proximal two thirds of right humerus in a young adult has completely disappeared, and distal portion of the shaft shows typical "sucked candy" attenuation. The glomus tumor was described in 1924 by Masson,105 who linked this peculiar neoplasm to a normal glomus body and proposed that in some cases it may represent a hyperplasia of perivascular cells rather than a true neoplasm. Definition Glomus tumor is a rare, benign distinctive neoplasm composed of vascular channels and modified perivascular muscle cells that recapitulate the structure of a glomus body. Incidence and Location Glomus tumors are extremely rare lesions, and most are diagnosed in patients between ages 20 and 40 years. A, Plain radiograph of chest of young man with disappearance of posterior portions of two upper ribs on left. B, Enlargement of radiograph shown in A with disappearance of posterior portions of two left ribs. Note multiple cystic spaces and replacement of bone by fibrous vascularized tissue. A, Amputation specimen showing large vascular structures representing tortuous thick-walled vasculature with cavernous dilations extensively involving the soft tissue of the lower extremity. B, T2-weighted magnetic resonance image showing grapelike high signal intensities corresponding to soft tissue vascular lesions. C, Higher power gross photograph of the foot showing extensive cystlike vascular lesions involving the soft tissue and eroding bones. B, Higher magnification of A shows cluster of perpendicularly sectioned glomic arterioles of Sucquet-Hoyer canals (arrows) surrounded by thick layer of glomus cells. Inset shows glomic arteriole surrounded by glomus cells and peripheral collecting vessel (denoted by asterisk). A and B, Radiographs of distal phalanges show pressure erosion of bone by subungual glomus tumors. Exposed concavity of tumor bed in distal phalanx can be seen just proximal to base of nail. Microscopic Findings Extraosseous glomus tumors are divided into three microscopically distinct subtypes: glomus tumor proper, glomangioma, and glomangiomyoma. The classification is based on differing proportions of vascular, smooth muscle, and epithelioid glomus cells. All the lesions reported as primary bone tumors have been of the glomus tumor proper category. The rich, branching vascular network can create a hemangiopericytoma-like pattern. A and B, Common pattern within glomus tumor is composed of solid sheets of cells with interspaced vessels. C, Low power photomicrograph shows large cystic spaces within solid sheets of tumor cells. D, Higher magnification of C shows tumor cells with eosinophilic cytoplasm and round or oval nuclei. Treatment and Behavior Glomus tumors are benign, and simple excision of both the soft tissue and intraosseous forms is curative. Malignant glomus tumor is extremely rare in soft tissue and has not been described in bone. Definition Epithelioid hemangioendothelioma is a unique, welldifferentiated endothelial vascular neoplasm with an epithelioid appearance of its endothelial cells and a tendency to be multifocal. Incidence and Location Epithelioid hemangioendotheliomas of bone are extremely rare. The limited experience with these lesions indicates that they most frequently occur during the second and third decades of life and there is a definite predominance in male patients. Most patients initially have multifocal lesions with a tendency to involve bones of the same region. Synchronous involvement of paired bones, most frequently the tibia and fibula, is common, but in some instances, completely separate synchronous foci are present in distant anatomic sites such as the clavicle and lumbar vertebrae. Occasionally a more aggressive growth pattern, such as a moth-eaten pattern, can be seen. Invasion into soft tissue is rare, and periosteal new bone formation is not present. In unusual circumstances, the epithelioid hemangioendothelioma can provoke sclerosis and may present as a blastic lesion on radiographs. Erosions of cortex with complete cortical disruption and extension into soft tissue can be present. Multifocal lesions involving one bone or several bones of an affected extremity are frequently seen. Later, in 1982, Weiss and Enzinger131 proposed the term epithelioid hemangioendothelioma to describe an unusual vascular tumor of soft tissue in which endothelial cells had an epithelioid appearance. Epithelioid hemangioendotheliomas are not unique to the soft tissue and occur in deep organs, most frequently the lungs and liver. They are classified as low-grade malignancies and have an indolent clinical behavior. Preliminary data indicate that this fusion is specific for epithelioid hemangioendothelioma regardless of its site of origin, including those that develop in bone and can be used in the differential diagnosis of vascular conditions with epithelioid features. A and B, Lytic sharply demarcated lesion of distal humerus with expansion of bone contour medially and posteriorly. E, Computed tomogram of lesion in D shows low signal intramedullary lesion with multiple erosions of cortex. B and C, Computed tomograms of lesions shown in A document multiple sharply demarcated lytic lesions of ilium. A-C, Extensive involvement of metatarsal bones with punched-out lytic lesions involving cortical bone and medullary cavities. D, Specimen radiograph of resected distal metatarsal segment containing lytic focus of epithelioid hemangioendothelioma. A, Anteroposterior radiograph of foot of an 18-year-old man with multiple lytic lesions of metatarsal and tarsal bones. B, Opposite foot of patient in A shows pathologic fracture of fourth metatarsal through focus of epithelioid hemangioendothelioma. Computed tomograms of right and left tarsal bones show multicentric, sharply demarcated lesions on right side. A and B, Anteroposterior and lateral radiographs of foot of young man show multiple lytic foci without reactive sclerosis or periosteal new bone formation involving metatarsals, phalanges, tarsal bones, and distal tibial shaft. A and B, Lateral and anteroposterior radiographs of leg of a 29-year-old woman show multiple small, sharply circumscribed lytic lesions of right tibia and fibula. C, Radionuclide scan of patient in A and B shows increased isotope uptake in multiple tarsal bones and distal tibia. D, Lateral radiograph of foot and ankle shows multiple lytic lesion in calcaneus and cuneiform bone. A, Lateral radiograph of leg show multiple sharply demarcated lytic lesions of tibia and tarsal bones. B, Magnetic resonance image showing multifocal well-demarcated low signal lesions involving distant tibia and tarsal bones. C, Gross photograph of bisected amputation specimen showing multifocal well-demarcated hemorrhagic lesions involving distal tibia and tarsal bones. A, Cut surface of distal segment of metatarsal bone containing intramedullary focus of epithelioid hemangioendothelioma eroding cortex in neck region. C, Resected head and shaft of proximal radius containing gelatinous, dark red lobulated tumor expanding into soft tissue. A, Solid nests of epithelioid endothelial cells and irregular open vascular channels. B, Higher magnification of A shows irregular vascular channel lined by epithelioid endothelial cells. D, Cords and small nests of epithelioid endothelial cells occasionally forming primitive vascular channels. B, Higher magnification of A shows epithelial endothelial cells forming ill-defined cords and nests. D, Higher magnification of C showing epithelioid endothelial cells lining vascular channels and forming cords. Focally, individual epithelioid cells are embedded in a basophilic matrix that mimics hyaline cartilage. Mitotic activity is low, within the range of 1 to 2 mitoses per 10 high-power fields. Tumors showing an abundance of mitoses, marked nuclear pleomorphism, and atypical, multipolar mitotic figures should be classified as angiosarcomas, with or without epithelioid features.

Once targeted hair loss dogs purchase discount finasteride on line, the stone is treated with repeated shock-wave bursts generated extracorporeally but focused internally on the stone hair loss finasteride generic 5mg finasteride. The stone fragments generally pass spontaneously in an antegrade fashion with voided urine hair loss guinea pigs order line finasteride. This coalescence of fragments is described as a stein strasse hair loss treatment at home discount finasteride 1mg fast delivery, translated as stone street hair loss cure 5 years cheap finasteride online american express. Rarely hair loss in men ripped order finasteride 1 mg with visa, more complex interventions are required to treat these obstructing stone casts. These interventions include ureteral dilatation, stone flushing, or long-term ureteral stenting. Complete discussion of these techniques is beyond the scope of this chapter, but the essential components will be described. B, Intraoperative radiograph following creation of a large-bore percutaneous tract with a sheath in place. C, Nephrostogram performed 6 weeks following endopyelotomy demonstrating marked decrease in the renal pelvic dilatation in comparison to the preoperative appearance. In either case, a guidewire should be advanced through the stricture and into a stable position. Angiographic catheters are useful in steering guidewires through tortuous or severely narrowed strictures. In addition, hydrophilic guidewires are extremely useful in traversing difficult ureteral strictures. Before balloon dilatation, a heavy-duty stiff guidewire should be advanced through the stricture. For tight strictures, before balloon dilatation an 8-F tapered angiographic catheter should be advanced through the stricture to predilate the stricture and allow for easy passage of the uninflated balloon catheter. This catheter is then removed and the balloon dilatation catheter positioned across the stricture. High-pressure balloons are often needed to successfully dilate ureteral strictures. For standard ureteroplasty procedures, 8- to 10-mm balloon dilatation catheters should be used. Therefore cyst aspiration is rarely used and thorough cross-sectional imaging should be performed before cyst aspiration is considered for diagnosis. Larger simple cysts may cause flank pain from compression of renal parenchyma, stretching of the renal capsule, or obstruction to urine outflow caused by mass effect. As with other transrenal procedures, routine coagulation factors should be analyzed and an appropriate antibiotic given before the procedure. Using standard sterile technique, the cyst is punctured with a fine (21- or 22-gauge) needle. As with cyst aspiration, the cyst should be evacuated and the fluid sent for analysis after its volume has been measured. Before ablation, a 4- or 5-F catheter should be placed within the cyst over a guidewire that can be inserted through the skinny needle. Before ablation can be undertaken, water-soluble contrast material should be injected into the cyst and fluoroscopic evaluation performed. Ablation should not be undertaken if there is extravasation outside the cyst or communication between the cyst and the intrarenal collecting system or blood vessels. For cyst ablation, a volume of absolute alcohol equal to 25% to 50% of the volume aspirated from the simple cyst is injected back into the cyst through the catheter. The sclerosant should be left within the cyst for approximately 10 minutes, during which time the patient should change position every 2 minutes to better distribute the alcohol around the entire lining of the cyst. After the 10-minute interval, all of the alcohol should be aspirated and the catheter removed. Cyst ablation usually causes minimal discomfort to the patient and can safely be performed as an outpatient procedure. This abdominal radio- graph taken following extracorporeal shock wave lithotripsy of a large renal stone demonstrates the typical appearance of a steinstrasse, which is a collection of stone fragments lodged in the ureter. The formation of a steinstrasse often heralds the development of ureteral obstruction. For antegrade balloon dilatation, an internal/external ureteral stent is advisable because repeated dilatations are often required for satisfactory long-term ureteral patency rates. Success rates for balloon ureteroplasty depend on the cause, the extent, and the chronicity of the stricture. In the ideal setting, which consists of a focal, acute stricture without associated ureteral devascularization, success rates are 90% or greater. This type of stricture is commonly seen in association with inadvertent ureteral ligation, which most often occurs during vaginal hysterectomy. On the opposite end of the spectrum of prognoses are strictures that occur at the junction of the ureter and a urinary bowel conduit. Some ureteral devascularization commonly occurs during the creation of urinary conduit diversions. Balloon ureteroplasty of strictures at the anastomotic sites usually has poor long-term patency rates. Long-term patency is achieved in only approximately 20% of patients after balloon dilatation of these strictures, even with multiple dilatations. Other strictures associated with poor ureteroplasty success rates include those caused by radiation therapy or neoplasms. However, because postoperative and Perinephric and Renal Abscess Drainage Management of retroperitoneal abscesses with percutaneous drainage has become routine in most radiology departments. Similarly, renal and perinephric abscesses are readily treated with a combination of percutaneous drainage and systemic administration of antibiotics. This contrast-infused computed tomography scan demonstrates a focal gas and fluid collection in the upper pole of the right kidney typical of emphysematous pyelonephritis. This type of emphysematous pyelonephritis may be remedied with percutaneous drainage and systemic antibiotic treatment. Extensive perinephric stranding is often coexistent because of surrounding inflammation and congestion. Initially, an 18-gauge needle is used to puncture the collection, aspirate a sample of material, and provide access for catheter placement. In equivocal cases, puncture and fluid aspiration can be performed for diagnosis and as a prelude to drain placement, if necessary. Drainage catheters are placed in a routine fashion using either trocar or Seldinger technique. For trocar technique, an 8-F or larger drain is advanced adjacent and parallel to the aspiration needle. Once the tip of the drain is confirmed to be in the abscess cavity, the drain is advanced off the trocar and the loop of the drainage catheter is reconstituted in the abscess. A drainage catheter 8-F or larger should be placed within the cavity for adequate drainage of the often viscous abscess contents. Once the catheter is placed, the abscess cavity should be evacuated by manually applying aspiration to the drainage catheter with a syringe. The catheter should then be connected to bulb suction or passive external drainage and sutured in place. The drainage catheter should be left in place until there is minimal output from the drainage catheter for a period of at least 12 hours, and the patient has recuperated without evidence of continued infection. In some cases multiple drains and transcatheter irrigation may be required to completely evacuate these abscesses. Focal emphysematous pyelonephritis is a special situation that can be treated with percutaneous drainage. Traditionally, all patients with emphysematous pyelonephritis were thought to require surgical nephrectomy; however, recent studies have suggested that a subgroup of these patients may be treated nonsurgically. The localized form of emphysematous pyelonephritis really represents a focal parenchymal abscess attributable to a gas-producing organism, and can be successfully treated with percutaneous drainage with systemic antibiotic administration. With percutaneous treatment of localized emphysematous pyelonephritis, it is essential that coexisting ureteral obstruction, if present, also be remedied to ensure infection resolution. Early treatment of localized emphysematous pyelonephritis can lead to complete resolution of the infection and normalization of function of the involved kidney. Alternatively, diffuse emphysematous pyelonephritis indicates irreversible damage to the majority of the kidney. Percutaneous Renal Biopsy Percutaneous renal biopsy is usually performed for one of two reasons: renal mass characterization or diagnosing medical renal disease. Because most renal masses can be accurately diagnosed with modern cross-sectional imaging techniques, biopsy is rarely necessary before treatment. Thus when percutaneous biopsy of a renal mass yields histologic evidence of an oncocytoma (a benign renal adenoma), a malignancy is still a possibility. Biopsy of geographic infiltrating renal masses, which are often transitional cell carcinomas, also poses a risk of seeding the biopsy track with metastatic deposits. Typically, this scenario relates to patients with lymphoma because renal lymphoma is not rare. In addition, renal lymphoma responds to chemotherapy and is not considered a surgical lesion. For these reasons, biopsy of a solitary renal mass in a patient with lymphoma is performed to distinguish a renal metastasis from a primary renal malignancy. Image-guided percutaneous renal mass biopsy is also performed to diagnose a renal mass in some patients with known metastatic disease. In these cases biopsy is used to distinguish a renal malignancy that has metastasized from an extrarenal malignancy that has seeded the kidney, before starting renal-tumor-specific hightoxicity treatment. In these patients a positive biopsy makes surgical treatment more imperative and may help the patient and surgeon assess the risks of surgery versus its potential benefits. A small number of patients have a propensity to develop multiple oncocytomas of the kidney. Although a biopsy of these new masses that yields benign oncocytes does not definitively exclude malignancy, it does strongly support the diagnosis of benign lesions. These patients should be followed closely with cross-sectional imaging at intervals no longer than 6 months. Any rapidly progressing lesions or lesions that develop imaging features atypical of oncocytomas should be considered highly suspicious for malignant tumors. The second group of patients who commonly undergo percutaneous biopsy are those with medical renal disease that requires tissue diagnosis. Typically, the renal biopsy should be obtained from the posterolateral aspect of the lower pole of either kidney. Core biopsies should be obtained, and the core should include some of the cortex of the kidney so that numerous glomeruli will be present in the sample. To reduce the risk of bleeding, the biopsy trajectory should remain peripheral and should not traverse the hilum or any visible vessels, nor should it traverse the far capsule. Automated biopsy guns or manually operating cutting needles can be used to obtain adequate samples. Percutaneous Cystostomy To expand on other percutaneous drainage techniques, radiologists may also perform percutaneous cystostomy with standard radiologic techniques learned in other interventional radiology applications. For short-term drainage, a small-bore (8- to 14-F) self-retaining drainage catheter can be used. Percutaneous cystostomy catheters are placed in patients with intractable incontinence, severe bladder outlet obstruction, or urethral laceration. In most of these settings percutaneous cystostomy catheters are used as a temporizing means before definitive surgical repair. The risks of percutaneous cystostomy placement are similar to those of other percutaneous drainage procedures and include a small risk of hemorrhage or infection. Percutaneous cystostomy is performed via a suprapubic needle puncture of the bladder that is performed near the midline. Once the puncture is performed, a small aliquot of urine should be aspirated to confirm transvesical puncture. A guidewire is then advanced into the bladder lumen and the tract dilated to an appropriate size for placement of the drainage catheter. For large-bore drain placement, a balloon dilatation catheter should be used to rapidly dilate the tract from 10- to 24-F with one balloon dilatation. This technique also minimizes the risk of dislodging the guidewire during repeated fascial dilatations. Once the tract is dilated, a sheath is placed through the tract over the guidewire, and a large-bore drainage catheter can be advanced into the bladder lumen. A Malecot, or standard bladder catheter with balloon retention device, can be used for drainage. The catheter should be sutured in place at the skin and left to external drainage. Follow-up cystography or voiding cystourethrography can be performed in an antegrade fashion via the percutaneous cystostomy catheter. Meanwhile, renal-sparing surgery has grown in popularity and the techniques have been refined. This indicates that complete eradication of a renal tumor can result in cure rates comparable to 384 GenitourinaryRadiology:TheRequisites utilizing complete removal of a kidney containing a tumor. Emission of this energy results in significant ionic agitation in tissues near the site of energy emission. The cell death is induced by denaturation of protein, melting of cell membranes, and thermal destruction of cytoplasm. When percutaneous thermal ablation of renal tumors is performed, imaging guidance is required. The actual treatment of the tumor can be quite painful, so more sedation is required than for a standard needle biopsy. Most cases are performed with conscious sedation and local anesthesia, or with general anesthesia.

In contrast to cartilage cells hair loss in men eyeglass 5mg finasteride with mastercard, notochord cells produce a thick basement membrane and retain hydrated materials in large vacuoles hair loss cure columbia order on line finasteride. The expression profiles characteristic of chordoid and chondroid lesions that may have diagnostic significance are summarized in Table 18-1 hair loss 7 years purchase finasteride american express. Muller performed a developmental study of human notochord and concluded that the "ecchordoses" were derived from the notochordal tissue hair loss 6 months after chemo buy finasteride australia. With the development of modern computerized imaging techniques hair loss 4 month old buy genuine finasteride on-line, they are more often identified before surgery during the diagnostic workup of the axial skeleton hair loss cure kidney buy finasteride 5 mg with mastercard. A, Fully developed notochord forming axial structure located anteriorly to neural tube. B, Notochord surrounded by sclerotomes forming ossification centers of vertebral column. D, Final stage of involution with residual notochordal tissue forming nucleus pulposus of intervertebral disks. A, Whole-mount photomicrograph of vertebral column from 3-month human embryo showing vertebral ossification centers with residual notochord forming disklike structures within the intervertebral cartilages. B, Higher magnification of residual notochordal tissue within an intervertebral cartilage. C and D, Residual notochordal tissue located in place of future nucleus pulposus showing cordlike arrangement of cells within myxoid stroma. The lesions are most frequently found in the clivus and sacrococcygeal vertebra followed by the cervical and lumbar spine. The distribution, depending on anatomic segments, is identical to that of classic chordomas. The oval cytoplasm of the notochordal cells shows various degree of vacuolization. Some of such rests can be composed of cells with extensively vacuolated cytoplasm that resemble fat or lipoma. The trabecular bone of the medulla is intact and the nests of notochordal cells grow between the trabecular spaces. The published reports and our own experience indicate that symtomatic notochordal rests typically measure at least 10 mm and may be multifocal involving several vertebral bodies. The trabecular bone is preserved but may show features of remodeling and sclorosis focally. Thickened trabecular bone may have central cores of hyaline cartilage with peripheral seams of partially calcified or ossified cartilage. The lesion has a nonagressive growth pattern with pushing borders and is sharply delineated from the adjacent tissue. A and B, Notochord rest of the clivus beneath sella turcica composed of uniform cells filling intertrabecular spaces with preservation of the trabecular bone. C, Higher magnification of A and B showing sheetlike proliferation of cells resembling fat with uniform mostly centrally located nuclei. B, Higher magnification of A showing overall architectural arrangement of the rest with preservation of the trabecular bone. C, Higher magnification of A and B showing sheetlike proliferation of notochordal cells with vacuolated cytoplasms resembling fat. The correlation of microscopic features with radiologic images helps avoid this error. Extensive bone destruction with associated paravertebral soft tissue mass is the hallmark of chordoma. Microscopically notochordal rests lack the lobulation, mucinous stromal pools, and syncytial cell chords characteristic of chordoma. In addition, cellular atypia and heterogeneity is lacking in benign notochordal lesions. The bone both trabecular and cortical is typically destroyed in chordomas and is intact or focally thickened in benign notochordal lesions. Some chordomas originate in the notochord rests, but it is unclear whether all tumors of this type arise from the persistent remnant of notochord tissue. Incidence and Location Chordoma is a relatively common tumor, accounting for 3% to 4% of primary malignant bone tumors in major series. A, A uniform sheetlike proliferation of notochordal cells filling up the intratrabecular spaces. B, Focus on thicken bone trabeculae with scallop borders forming interconnecting network, signifying bone remodeling frequently seen in giant notochord rest. C, Solid sheetlike proliferation of notochordal cells with clear cytoplasm resembling fat. D, Pushing border sharply delimiting the notochord cells from the adjacent, uninvolved fatty marrow. Inset, Higher magnification of a physaliphorous cell typically present in notochord rests. A and B, Whole-mount photomicrographs of coccyx showing a giant notochord rest and a focus of chordoma (arrows). Note that focus of chordoma shows distinctive lobular architecture with myxoid stromal change and exhibits destructive growth pattern, breaking through the cortex into the periosteal fibroadipose tissue. B, Higher magnifications of A and B showing a focus of chordoma with lobular architecture and myxoid stroma. C, Higher magnification of A showing chordoma cells infiltrating periosteal stromal tissue. D, Higher magnification of B showing chordoma cells infiltrating periosteal stromal tissue. Inset, Microscopic features of giant notochordal cells with solid sheetlike proliferation of bland looking notochordal cells with clear cytoplasm resembling fat. A, Gadolinium-diethylenetriamine pentaacetic acid enhanced T1-weighted magnetic resonance image. Tumor protrudes anteriorly from the coccyx and consists of intermediate density lobules separated by thin contrasted septations. Two intraosseous lesions of low density corresponding to notochord rests are identified (arrows). B, Gross photograph of the resected specimen discloses a lobulated tumor composed of gelatinous tissue with foci of hemorrhage. Two intraosseous lesions corresponding to multifocal giant notochord rests are also present (arrows). C, Microscopic features of a giant notochord rest showing sheetlike solid proliferation of cells with vacuolated cytoplasm. D, Microscopic features of notochordal rest (upper part) and chordoma (lower part). Note myxoid appearance of stroma in chordoma and bland looking solid proliferation of benign notochord cells. It must be mentioned that a small number of chordomas occur during the first and second decades of life. Chordoma almost exclusively involves the axial skeleton, which is in keeping with its notochordal origin. Extremely rare examples of multicentric chordoma involving several anatomic sites have been reported. Sphenooccipital chordomas produce symptoms related to compression or destruction of various adjacent structures, such as the optic nerves or pituitary gland. Age-adjusted incidence rates and age-specific frequency, all races, both sexes, 650 cases. A, Anteroposterior radiograph of sacrum shows expansive lytic lesion of body of sacrum. B, Lateral radiograph of lumbar spine shows unusual sclerotic appearance of body of L4 produced by vertebral chordoma. Lateral view of skull shows destruction of sella turcica region of base produced by sphenooccipital chordoma (arrow). T2-weighted magnetic resonance image of chordoma at base of skull shows high signal intensity mass in region of sphenoid bone (arrows). Vertebral chordomas produce lytic lesions that may involve two or more adjacent vertebral bodies. Computed tomography and magnetic resonance imaging are indispensable in evaluating both the extent of the lesion and the involvement of adjacent structures. They are frequently myxoid or gelatinous in appearance and can mimic chondrosarcoma or mucinous adenocarcinoma. Despite good demarcation, the tumor usually extends beyond its grossly recognizable borders. Chordomas often involve the medullary canal, compressing the spinal cord and its nerves. The level of cellularity can vary considerably among cases and in different areas of the same tumor. More often, there is a moderate amount of cellular tissue and clearly recognizable intercellular myxoid stroma. In general, most chordomas exhibit clearly recognizable nuclear pleomorphism with occasional large atypical cells. Frequently, it is in the form of large (single or several) vacuoles displacing the nucleus peripherally and causing the so-called signetring-like appearance of the tumor cells. Occasionally, the vacuoles encircle the nucleus, which remains centered in the cytoplasm and produces the so-called physaliphorous appearance. It must be mentioned, however, that classic physaliphorous cells, as they are frequently illustrated in many pathology textbooks, are relatively sparse or may not be present at all in otherwise typical chordoma. The classic large physaliphorous cell has a centrally located nucleus surrounded by a narrow rim of cytoplasm that in turn, is encircled by a ring of more peripherally located cytoplasmic vacuoles. Such lesions are descriptively referred to as lipoma-like chordomas and may be confused with benign or malignant lipomatous tumors. On the other hand, highly cellular lesions with minimal vacuolization and dense eosinophilic cytoplasm may mimic epithelial neoplasms. Areas of cartilage can range from small microscopic foci to large prominent areas. Therefore chordomas can be occasionally difficult to distinguish from chondrosarcoma. The term chondroid chordoma has been proposed to designate hybrid lesions that exhibit features of both lesions-chordoma and chondrosarcoma. The controversy over this entity and its potential for clinical significance are discussed separately. The presence of abnormal multivacuolated cytoplasm with centrally placed, scalloped nucleus (that is, physaliphorous cells) is the hallmark of chordoma. Such classical cells are, however, rare; in the vast majority, the cells show dense eosinophilic cytoplasm or are lipoblast-like with single or several larger cytoplasmic vacuoles displacing the nucleus peripherally. Cytologic features combined with radiologic and clinical presentation allow correct cytologic diagnosis in most cases of chordoma. The immunohistochemical features such as coexpression of epithelial markers and S-100 protein can be also tested in cytologic preparations. Chordoma cells contain intermediate filaments and are connected by desmosome-like junctions. The extracellular matrix consists of a fine, granular substance of low electron density. A, Computed tomography shows lobulated mass protruding posteriorly and anteriorly from origin in sacrococcygeal junction. B, T1-weighted sagittal magnetic resonance image of chordoma shown in A with larger posterior and anterior low signal mass (arrows). Lateral radiograph of cervical spine shows destructive lesion of body of C2 (arrows). In general chordoma recapitulate a gene expression signature of notochordal cells. Among all of the markers, brachyury appears to be the most specific for chordoma and notochordal tissue and is useful in the differential diagnosis. The most common cytogenetic abnormality is hypodiploidy with loss of the short arm of chromosome 3, and loss of proximal 1p as well as monosomy of chromosome 10. Chordomas are also characterized by frequent gains of genetic material on 5q, 7q, 12q, and 20q. The cytogenetic data suggests that tumor suppressor genes on 1p and 3q as well as oncogenes mapping to 5q, 7q, 12q, and 20q may play a role in the development of these tumors. The presence of physaliphorous cells and a trabecular or cordlike arrangement together with a myxoid matrix are typical for chordoma. However, conventional chondrosarcoma occasionally may show a cordlike arrangement of cells and myxoid stroma. In such instances, positivity for S-100 protein and negative staining for epithelial markers favor chondrosarcoma. Other myxoid bone tumors, such as chondromyxoid fibroma, which rarely occurs in the axial skeleton, are very unlikely to be confused with chordoma. Highly cellular areas with cohesive solid cellular sheets and prominent nuclear atypia can be confused, especially in a limited biopsy specimen, with an epithelial neoplasm. Extensive clear-cell change and the signet-ring appearance of chordoma cells can lead to a misdiagnosis of metastatic adenocarcinoma or less frequently lipomatous tumor. Among various epithelial tumors metastatic to the skeleton a chromophobe variant of renal cell carcinoma may superficially resemble a chordoma. Strict adherence to clinical and radiographic data usually helps to avoid this error. A, Axial computed tomography shows destructive mass protruding posteriorly and anteriorly from the sacrum (arrows). B, T1-weighted sagittal magnetic resonance image of chordoma shown in A with predominantly anterior low signal mass (arrows). C, Sagitally cut resection specimen of the tumor shown in A and B demonstrates a lobulated, fleshy tumor mass destroying the sacrum and extending to the soft tissue anteriorly and posteriorly. D, Histologic section of same tumor shows cords of chordoma cells with multivesicular cytoplasm growing in a myxoid stroma.

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E hair loss 1 year after childbirth order finasteride 1mg fast delivery, Gross photograph of the same case shown in C and D shows intramedullary mass permeating overlying thickened cortex with subperiosteal mass hair loss in men xmas order finasteride 1mg amex. A hair loss treatment dubai purchase finasteride 1mg fast delivery, Permeative lesion of proximal femoral shaft associated with cortical thickening hair loss cure 2014 histogen cheap finasteride 1mg on line. Magnetic resonance imaging and computed tomography permit more accurate preoperative assessment of the lesion than plain radiographs hair loss cure genetic buy discount finasteride 1mg. They typically demonstrate intramedullary lesions that involve large segments of the intramedullary cavity and extend beyond the area shown to be involved on plain radiographs hair loss cure that works buy discount finasteride 1mg online. This type of radiographic appearance is typically seen in predominantly subperiosteal lesions. The sclerotic features or focal opacities are more often seen in lesions involving the metaphyseal portions of long bones or in flat bones and are practically never seen in diaphyseal lesions. On the other hand, diaphyseal lesions of long bones are often associated with diffuse sclerosis and thickening of the overlying cortex. The tumor can involve large segments of the medullary cavity without causing cortical disruption. Although complete cortical disruption is not a characteristic feature, the cortex is typically permeated by small nests of the tumor. Formation of a large extraosseous mass, which often exceeds the size of the intraosseous component, is frequently seen. The cells grow in solid, densely packed sheets and nests filling intertrabecular spaces. The nuclear chromatin is finely granular, and there are usually one to three clearly identifiable small- to intermediate-sized nucleoli. The cytoplasm is indistinct and forms an ill-defined narrow rim around the nucleus. Often a biphasic pattern is simulated by the presence of so-called dark cells and light cells. These types of cells are sometimes referred to as principal (light) and secondary (dark) cells, respectively. The ratio between these two types of cells varies from tumor to tumor and in different areas of the same lesion. In some tumors, cords or clusters of dark apoptotic cells form an interconnecting network of irregular patches that create a pseudoorganoid pattern. Complete permeation of the cortex and its eventual disruption are associated with the formation of a mass that initially forms subperiosteally and then extends into soft tissue (parosteal). Penetration of the cortex and disturbance of the periosteum are associated with new bone formation. The proportion of stromal reticular elements and blood vessels is increased near the advancing edge of the tumor compared with its more central intramedullary portion. Multilayered periosteal new bone formation, corresponding to an identifiable onion-skin appearance on radiographs, can accompany the advancing tumor cells. Periosteal bone formation is associated with plump reactive osteoblasts and multinucleated osteoclast-like giant cells and may have foci of cartilage metaplasia. Peripheral areas of the tumor within soft tissue may show more dispersed tumor cells invading collagenized stroma, adipose tissue, and skeletal muscle. Occasionally, a distinct growth pattern in the form of larger lobules or nests composed of compact tumor cells and separated by fibrous septa can be seen. This is usually present within the extraosseous component and is rarely seen within the intramedullary portion of the lesion. Vascular formation in the central portion is inconspicuous and is represented by slitlike capillaries with fine endothelial cells among tumor cells. Larger, thick-walled vessels can be seen within stromal bands separating tumor cells. The morphologic features of cells, and especially the details of the nuclei, are often Text continued on p. A Computed tomogram shows intramedullary tumor with cortical disruption posteriorly and extension into soft tissue. B and C, Anteroposterior and lateral plain radiographs show permeative lesion in metaphyseal region; so-called cortical saucerization (concave defect) can be seen on posterior surface in C. A, Large destructive tumor of body and glenoid regions of scapula with associated soft tissue mass. This atypical plain radiographic appearance was interpreted initially as probable vascular tumor. C, Expansile tumor with moth-eaten pattern of bone destruction in distal end of fibula in young adult. B, Radiograph of amputation specimen shows destruction of proximal plate of great toe and ill-defined soft tissue mass. C, Permeative destructive lesion involving entire shaft of proximal phalanx of finger is shown in this oblique radiograph. A, Lateral radiograph of ankle and foot of young adult shows rarefaction of posterior part of os calcis. B, Anteroposterior radiograph shows permeative destruction of cancellous bone with ill-defined border. C, Technetium 99 bone scan shows high uptake of isotope in os calcis, which is more intense posteriorly. Although distal tibia showed increased isotope uptake, tumor was not present in this site. A and B, Plain radiographs show destructive lytic mass of proximal tibia with increase of new periosteal bone formation. A and B, Coronal and sagittal computed tomograms showing a large tumor involving the upper portions of the left thoracic wall and pulmonary cavity. C and D, Axial and sagittal magnetic resonance images showing a large low signal intensity tumor involving the left paraspinal region and thoracic wall. Proximal circumferential soft tissue extension with elevation of periosteum is evident. Note large subperiosteal lesion with concave cortical surface; defect is referred to as saucerization. Intramedullary tan-gray tumor with posterior subperiosteal and soft tissue extension associated with concave cortical defect. C, Closer view of specimen shown in B shows intramedullary tumor with cortical permeation and periosteal elevation. Stroma is minimal and confined to few delicate fibrous tissue strands and blood vessels. D, Higher magnification of C shows uniform tumor cells with minimal amount of cytoplasm. Inset, High power photomicrograph of Homer Wright rosette consisting of a central fibrillar core bounded by concentrically arranged tumor cells. Note the presence of apoptotic dark cells at the interphase of viable and necrotic tumor. D, Higher magnification of the interphase between viable and necrotic tumor tissue showing prominent dark apoptotic cells. In a small number of tumors, the microscopic appearance of tumor cells may deviate from the so-called classic pattern. These features are more often seen in recurrent and treated lesions but can also be present in primary tumors. A delicate, finely granular chromatin pattern and clearly identifiable small to medium nucleoli are characteristic. Immunohistochemical and molecular study allowing differential diagnosis with other small cell malignances may be performed on material obtained for cytologic preparations. The cellularity is high, and the tumor cells are densely packed with almost nonexistent stroma. Two types of cells as defined by light microscopy-a principal type (light with open intact chromatin) and a secondary type (dark with condensed chromatin)-can also be recognized at the ultrastructural level. Minimal amounts of stromal elements associated with endothelial-lined capillaries and occasional larger vessels are seen focally. Centrally located nuclei are oval to round and have outlines with occasional indentations of the nuclear membrane. Some intracytoplasmic reticulum and poorly developed small Golgi centers are present. Ultrastructurally, there is a continuous transition from intact principal cells to dark apoptotic cells, and in some areas, the so-called dark cells can predominate. The ultrastructure of the dark cells may show all the features of nuclear condensation and segmentation described for apoptosis. Before the advent of chemotherapy, the prognosis was dismal, with a 5-year survival rate of less than 20%. The use of multimodality treatment plans of irradiation and multidrug chemotherapy plus surgery has significantly changed this survival rate. Those patients who initially have localized, resectable disease and are treated with multidrug chemotherapy in addition to surgery have a 5-year survival rate of approximately 70%. A-D, Fine-needle aspirate containing undifferentiated round cells with occasional nucleoli and indistinct cytoplasm, occasionally forming rosette-like structures (arrows). Inset, Rosettelike structure formed by circumferential arrangement of tumor cells around central core containing delicate fibrillar cytoplasmic material. A and B, Undifferentiated mesenchymal cells containing sparse cytoplasmic organelles and prominent deposits of glycogen. A, Undifferentiated tumor cells containing sparse cytoplasmic organelles and regular round nuclei with freely dispersed chromatin on occasional nucleoli. Similar to osteosarcoma, it has been shown that surgical removal of the resectable lung metastases improves survival. The incidence of disseminated disease at the time of diagnosis is high, and approximately 15% to 28% of patients initially have metastatic disease. Patients who have resectable lesions of the extremity bones have a better survival rate than those who have lesions affecting the trunk bones, such as the pelvis and the thoracopulmonary region. In addition, lesions in the latter sites are significantly larger at presentation and show extensive soft tissue involvement. Extensive spontaneous necrosis of untreated lesions is a predictor of more aggressive clinical behavior and is linked to lower survival rates. Its presence is considered by some authors to be synonymous with invasion into soft tissue and may signify a higher stage and volume of lesions. Favorable response, which is defined as total or subtotal (90% to 100%) necrosis, appears to be a strong predictor of long-term survival. The link between favorable prognosis and good chemotherapy response has been consistently shown in several independent studies. Moreover, the degree of postchemotherapy necrosis seems to correlate with the rate of disease-free survival. In a study from the Rizzoli Institute, the 5-year disease-free survival rate was 90% for patients with complete necrosis, 53% for those with microscopic residual tumors, and 32% for those whose lesions had gross evidence of residual tumor. Immunohistochemical features of overexpression of the genes involved in the development of drug resistance, such as P glycoprotein, show some promising results, but too few cases have been studied to assess the practical application of these findings. These types of rosettes should not be used as sole microscopic evidence of neural differentiation. Sparse neurosecretory granules are associated with both developing Golgi centers and cell processes. In a recent interinstitutional study involving several centers in the United States and Europe, the analysis of 315 cases showed no association between neural differentiation and more aggressive behavior. In the original report, the authors postulated that this lesion had a distinct pathogenesis and apparently arose in the ribs, predominantly in the periosteum, but could also arise in the soft tissue, and possibly within the lung. The lesions are frequently positive for one or several of the so-called neural markers, including neuron-specific enolase and neurofilaments of 70 kD, and may also express neuroendocrine markers such as chromogranin. The unique features seem to be frequent primitive neural or neuroendocrine differentiation, as well as focal epithelial differentiation. A, Tumor cells with sparse cytoplasmic organelles as seen on low power magnification. B, Centrally placed cytoplasmic processes correspond to core of rosette (asterisk). A, Axonal differentiation of tumor cells with formation of interconnecting cytoplasmic processes (arrows). These two antibodies identify the antigen in formalin-fixed, paraffin-embedded tissue. It is also positive in pediatric lymphomas, lymphocytic lymphoma, and occasionally in rhabdomyosarcoma and even synovial sarcoma. Positivity for neuron-specific enolase is generally disregarded as a specific marker of neural differentiation. On the other hand, if its expression can be correlated with other features of neural differentiation, it provides a valuable tool with which to assess the degree of neural phenotypic expression. A, Intermediate power view of small round-cell tumor with sparse stromal elements. Scattered positivity of individual tumor cells for keratins can be seen in approximately 10% of these tumors. In general, the differential diagnosis of small round-cell tumors of bone include not only the entities described in this chapter, but also a variety of mesenchymal and epithelial (primary and metastatic) tumors that may occur in children, adolescents, and adults. It is recommended that rendering such a diagnosis in an unusual clinical setting should be verified by molecular testing.