Recombinant human granulocyte colony-stimulating factor. Effects on hematopoiesis in normal and cyclophosphamide-treated primates.

We examined the in vivo effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in primates (cynomolgus monkeys) treated with subcutaneous doses of rhG-CSF for 14-28 d. A dose-dependent increase in the peripheral white blood cells (WBC) was seen, reaching a plateau after 1 wk of rhG-CSF treatment. The elevation of WBC was due to an increase in the absolute neutrophil count. These results demonstrate that rhG-CSF is a potent granulopoietic growth and differentiation factor in vivo. In cyclophosphamide (CY)-induced myelosuppression, rhG-CSF was able to shorten the time period of WBC recovery in two treated monkeys to 1 wk, as compared to more than 4 wk for the control monkey. Its ability to significantly shorten the period of chemotherapy-induced bone marrow hypoplasia may allow clinicians to increase the frequency or dosage of chemotherapeutic agents. In addition, the increase in absolute numbers of functionally active neutrophils may have a profound effect in the rate and severity of neutropenia-related sepsis. Furthermore, the activities reported here indicate a potential role for rhG-CSF in the treatment of patients with myelodysplastic syndrome, congenital agranulocytosis, radiation-induced myelosuppression, and bone marrow transplantation.

Action of 1,25-(OH)2D3 in nude mice bearing transplantable human myelogenous leukemic cell lines.

After cyclophosphamide priming, subcutaneously (s.c.) transplanted cells from established human leukemia cell lines U937, K562, or HL-60 consistently yielded single, nonmetastatic tumors. Tumorigenesis with KG-1 cells was inconstant. Within each cell line, cytologic, electron-microscopic, cytogenetic, isoenzyme, immunochemical, and enzyme cytochemical studies confirmed identity of cultured and tumor cells. Adenosine triphosphatase reactivity was limited to leukemic cells in vivo. Isoenzyme electrophoretic patterns, distinct for each cell line, provided a reliable criterion to establish clonality and to verify tumor cell origin. Antitumor activity of the active vitamin-D3 metabolite 1,25-(OH)2D3 was assessed in vivo against U937, K562, and HL-60 cells by cell transplantation and concurrent s.c. contralateral implantation of miniosmotic pumps containing the 1,25-(OH)2D3 in a propylene glycol vehicle. Tumors developed in all treated U937 mice, 50% with K562 and 25% bearing HL-60 transplants. All transplants proliferated in mice either with pumps containing only vehicle or no pumps. Coincidence of tumor and vehicle decreased survival time. No differences in cytoreactivities or morphology were apparent between cultured cells and tumor cells in treated or untreated mice. This nude mouse system is useful for in vivo studies of human myelogenous leukemia cells. Implanted miniosmotic pumps provide controlled delivery of antineoplastic agents and their vehicles for in vivo studies. 1,25-(OH)2D3 may be a valuable adjunctive therapeutic for control of human myelogenous leukemias.

Silicone elastomer microshards in fluid from a painful metatarsophalangeal implant site. A case report.

Histopathologic studies have demonstrated microshards from silicone elastomer metatarsophalangeal joint implants in adjacent tissues in a setting of chronic inflammation and in inguinal lymph nodes. Cytologic smears of synovial fluid from symptomatic implanted joints should show these refractile, nonpolarizing microshards in the reactive inflammatory context. Nonspecific enzymatic inflammatory activity contributes to further destabilization of the implants, eventuating in symptoms and signs requiring prosthesis removal. Cytopathologic examination of aspirated fluid from the vicinity of a symptomatic implanted joint demonstrates foreign body reaction to silicone elastomer, predicting a need for intervention before the local damage is severe and disabling.

Chondroid syringoma in a toe.

The second case of chondroid syringoma in a toe is presented. The diagnosis was confirmed microscopically, and histochemical studies suggested the presence of heavily sulfated stromal acid mucopolysaccharides. Glycogen was present only in some tumor cells. Keratin-containing tumor cells and nests were seen with polarization. This tumor should be considered in the differential diagnosis of painless, slow-growing, pedal tumors.

Progressive pedal macrodactyly surgical history with 15 year follow-up.

Macrodactyly can affect the fingers and/or toes1. Histopathologic examination will distinguish macrodactylia fibrolipomatosis or neural fibrolipoma with macrodactyly, from macrodactylia as a part of neurofibromatosis. Surgical repair is aimed at decreasing the size of the affected foot so it is as near in size and shape to the normal foot as possible. Surgical approaches have included reconstructive surgery (usually staged debulking procedures), epiphyseal plate arrest and amputation. Repeated reconstructive surgical procedures, as illustrated in this report covering patient care over a 15 year period, are usually necessary due to recurring soft tissue and boney enlargement.

Evaluation of a patient for pedal neoplasia. Basic principles and procedures.

The process of determining a diagnosis for a patient with a tumor mass is not easy. It demands astuteness on the part of the attending doctor as well as cooperative consultation and teamwork with radiologists, pathologists, and other specialists. It also demands a basic understanding of the characteristics of benign and malignant tumors in the foot, whether primary or metastatic. This is best accomplished by continued reading of a variety of journals and current texts as well as by attendance at clinical conferences. Concern for the patient must motivate any practitioner to know, understand, and undertake definitive diagnostic procedures to determine the nature and extent of a neoplasm. The practitioner must acquire and maintain an appropriately high index of suspicion and an awareness that the foot can be the site of a primary or metastatic tumor.

Neoplasia in the toes and toenail areas.

Benign and malignant tumors as well as pseudotumors occur in the toes. The toenail areas may also be involved primarily or secondarily. All tissues in the toes can give rise to tumors. Occasionally, metastatic tumors from the viscera manifest in the toes. New or recurrent masses should be subjected to biopsy, as should lesions that do not respond to treatment based on an initial clinical impression.

Neoplasms of the peripheral nervous system.

Neoplasms of the peripheral nervous system arise from the cellular sheath surrounding the nerve trunks, that is, the pluripotential Schwann cells and related cells, and rarely affect the feet. When present, they are most frequently associated with the autosomal dominantly inherited neurofibromatosis 1. This condition has been related to chromosome 17, and it appears, from in vitro experiments, to involve defects in tyrosine metabolism. Hence, the most common neoplasm is the neurofibroma. Distinct criteria have been established for a diagnosis of neurofibromatosis 1, so that a single pedal neurofibroma may not represent this complex. However, if the complex is present, it is necessary to consider the possibility of malignant transformation to a neurofibrosarcoma. Although malignant peripheral nerve neoplasms are extremely rare in the feet, they may arise in the context of neurofibromatosis 1, or independently. Other benign or malignant schwannomas may (rarely) also arise in the feet. Surgical excision of benign lesions, according to established standards for tumor surgery, is usually curative, but a detailed personal and familial history, along with adjunctive radiologic procedures and biopsy, is necessary to determine the nature of the lesion. Since (endocrine and) other abnormalities may complicate neurofibromatosis 1, surgical procedures must not be undertaken until the patient has been medically cleared and is carefully monitored. A high mortality rate is associated with malignant peripheral neurogenic tumors, especially those arising in the context of neurofibromatosis 1. It should be recalled that neurologic manifestations in the foot may represent non-neoplastic conditions as well as peripheral nerve tumors (or other tumors involving those nerves) that are proximal to the foot and ankle area.

Primary and metastatic malignant tumors in soft tissue of skin. Diagnostic, surgical, and prognostic considerations for the foot.

Benign and malignant soft-tissue tumors are those that arise from mesenchymal (and some neuroectodermal) nonosteogenic and nonchondrogenic cells. The various primary malignant tumors are sarcomas with invasive and metastatic potential and are the same types that arise in the deeper tissues. In addition to sarcomas that arise directly in the dermis or subcutis, these tissue areas may be invaded by sarcomas from the deeper structures and by carcinomas and sarcomas metastatic to the skin. Dermal or subcutaneous cancers may appear clinically nondescript but are nonetheless dangerous, requiring an appropriately considered biopsy for identification and subsequent planning of patient care.

Review and consideration of coagulopathies.

Blood components bring nutrients to the tissues, remove wastes, provide defenses against microorganisms and foreign bodies, and retain sufficient fluidity to keep the system functioning properly. Coagulation factors are also present in the blood as part of a sensitive system that stems the flow of blood from a wound and maintains homeostasis. These factors include anuclear platelets that originate from megakaryocytes in the bone marrow, as well as soluble factors in precursor form, and calcium ion. Faults in single or multiple parts of this system, which can be determined in the patient's history, may result in bleeding problems that may be clinically relevant. Clarification of coagulation defects requires cooperation with a hematologist before medication that affects the coagulation system is prescribed or before any procedures that may result in bleeding are undertaken.

Considerations in the treatment of patients with renal disease.

Renal function includes maintenance of fluid pH, electrolyte and fluid balance, influence on blood pressure, excretion of fluid and metabolic soluble wastes after filtration or reabsorption, and production of erythrocyte stimulating factor and the active form of vitamin D. These processes involve sensory mechanisms in the kidney, as well as the ability to respond to sensed changes, to maintain body homeostasis. Decrease in or failure of renal function induces abnormalities in many other systems, requiring a modified approach that is individual to each patient, and includes alteration of medications used and a re-evaluation of their doses. Some patients may require a regimen of dialysis or eventual renal transplantation, each with attendant advantages and risks. Careful evaluation and consultation with a nephrologist is required when local or systemic treatment is contemplated.

Keratoacanthoma: case presentation and discussion.

Keratoacanthomas are rather common, rapid growing skin tumors, in which may occur as solitary lesions or in the form of multiple lesions. Multiple forms involve the palms of soles, and their source is unclear. On area where hair grows, these lesions originate from the infundibular areas. Many environmental and traumatic influences are implicated as potential etiologic factors. Keratoacanthomas should be differentiated clinically and histologically from squamous cell carcinomas, prurigo nodularis, and chronic paronychia. Treatment varies according to the type of lesions, but solitary lesions should be excised in toto.

Nude mice as models for human leukemia studies.

Human leukemic promyelocytes of the HL-60 line were grown as tumors in nude mice and studied. A single nonmetastatic granulocytic sarcoma developed after subcutaneous inoculation with HL-60 cells. Some exceeded 5 cm in size. Almost all mice developed tumors after initial priming with cyclophosphamide. Older sarcomas showed viable tumor islands in necrotic and fibrotic tissue. Some tumors appeared greenish. Histologic and electron-microscopic analysis demonstrated large, vaguely outlined cells in poorly vascularized sheets. The cells displayed high nucleocytoplasmic ratios, basophilic granular cytoplasms lacking Auer rods, and enzymes characteristic of cultured HL-60 promyelocytes. Some tumor cells also demonstrated monocyte/macrophage enzymes, such as butyrate esterase. Induced HL-60 tumors also corresponded morphologically to a human subcutaneous promyelocytic tumor specimen. Comparative cytologic studies of induced HL-60 tumors in nude mice and cultured HL-60 cells revealed virtual identity, suggesting the nude mouse tumor as a useful model for in vivo studies of human leukemic cells.

Dermatofibrosarcoma protuberans: 4 years after local trauma.

Dermatofibrosarcoma protuberans (DFSP) is a low grade, fibrohistiocytic malignant soft tissue tumor that arises infrequently in the foot and ankle region. It most frequently demonstrates a "storiform" histologic pattern, and if incompletely excised, may be recurrent, more anaplastic and metastatic. Soft tissue plain film radiography, as well as magnetic resonance imaging (MRI) help outline the tumor and involved tissues, which is beneficial in staging, determining surgical approach and evaluation of therapy. Definitive diagnosis is made by biopsy. A dermatofibrosarcoma protuberans is reported in the foot of a 14-year-old female patient, 4 years after trauma to the site.

Delayed appearance of metastatic renal cell carcinoma subcutaneously in the left fifth toe after ipsilateral nephrectomy.

Pedal metastases from visceral cancers, while rare, constitute a consideration in the presence of an otherwise unexplained mass in the skin, subcutis, or bones of the foot. Metastatic lesions may be presenting signs of visceral malignant tumors, or may remain occult for years after extirpation of the primary visceral lesion. The presented case depicts sudden activation and growth of an occult renal cell carcinoma metastasis in the subcutaneous tissue of a 69-year-old man's left fifth toe, 10 years after ipsilateral nephrectomy. Cytogenetic studies correlate with tumor histologic patterns and help to predict heritability, uni- or bilaterality, and local and systemic biologic behavior of renal cell carcinoma, thereby aiding in prognosis and treatment planning.