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Synthetic vitreous fibers: a review of toxicology research and its impact on hazard classification.

Because the inhalation of asbestos, a naturally occurring, inorganic fibrous material, is associated with lung fibrosis and thoracic cancers, concerns have been raised about the possible health effects of synthetic vitreous fibers (SVFs). SVFs include a very broad variety of inorganic fibrous materials with an amorphous molecular structure. Traditionally, SVFs have been divided into three subcategories based on composition: fiberglass, mineral wool (rock, stone, and slag wools), and refractory ceramic fiber. For more than 50 years, the toxicologic potential of SVFs has been researched extensively using human epidemiology and a variety of laboratory studies. Here we review the research and its impact on hazard classification and regulation of SVFs. Large, ongoing epidemiology studies of SVF manufacturing workers have provided very little evidence of harmful effects in humans. Several decades of research using rodents exposed by inhalation have confirmed that SVF pulmonary effects are determined by the "Three D's", fiber dose (lung), dimension, and durability. Lung dose over time is determined by fiber deposition and biopersistence in the lung. Deposition is inversely related to fiber diameter. Biopersistence is directly related to fiber length and inversely related to fiber dissolution and fragmentation rates. Inhaled short fibers are cleared from the lung relatively quickly by mobile phagocytic cells, but long fibers persist until they dissolve or fragment. In contrast to asbestos, most of the SVFs tested in rodent inhalation studies cleared rapidly from the lung (were nonbiopersistent) and were innocuous. However, several relativley biopersistent SVFs induced chronic inflammation, lung scarring (fibrosis), and thoracic neoplasms. Thus, biopersistence of fibers is now generally recognized as a key determinant of the toxicologic potential of SVFs. In vitro dissolution of fibers in simulated extracellular fluid correlates fairly well with fiber biopersistence in the lung and pulmonary toxicity, but several exceptions suggest that biopersistence involves more than dissolution rate. Research demonstrating the relationship between biopersistence and SVF toxicity has provided a scientific basis for hazard classification and regulation of SVFs. For a nonhazardous classification, legislation recently passed by the European Union requires a respirable insulation wool to have a low lung-biopersistence or be noncarcinogenic in laboratory rats. U.S. fiberglass and mineral wool industries and the Occupational Health and Safety Administration (OSHA) have formed a voluntary Health and Safety Partnership Program (HSPP) that include: a voluntary permissible exposure level (PEL) in the workplace of 1 fiber/cc, a respiratory protection program for specified tasks, continued workplace air monitoring, and, where possible, the development of fiber formulations that do not persist in the lung. RCF manufacturers have implemented a Product Stewardship Program that includes: a recommended exposure guideline of 0.5 fibers/cc; a 5-year workplace air monitoring program; and research into the development of high-temperature-resistant, biosoluble fibers.

Animals↗

Pediatric fine-needle aspiration biopsy.

A total of 135 fine-needle aspiration (FNA) biopsies from varying sites were performed in 123 children (mean, 10.5 years; range, one day to 18 years) over a five-year period. One hundred thirty (96.3%) biopsy specimens were satisfactory for evaluation. Seventy-nine cases were nonneoplastic (60.8%); among these cases, a specific diagnosis of infectious disease was made in 17 (13.1%). A diagnosis of neoplastic disease was made in 50 (38.5%) cases, of which 14 (10.8%) were benign, 28 (21.5%) were malignant, and 8 (6.2%) were neoplasms of uncertain biologic potential. The sensitivity of pediatric FNA biopsies was 90.6%, specificity 100%, positive predictive value 100%, negative predictive value 94.7%, and efficiency of the test 96.5%. There were no false-positive diagnoses and there were four false-negative diagnoses, three of which involved aspirates of the central nervous system (CNS). Ancillary studies, including immunocytochemistry (20 cases), electron microscopic examination (18 cases), microbiologic culture (8 cases), cytogenetic studies (7 cases), and flow cytometry (3 cases), were performed on the aspirated material, enabling a more specific diagnosis or supplying additional information in many cases. Definitive diagnosis by FNA biopsy enabled radiation therapy and/or chemotherapy to be administered for unresectable malignant neoplasms, provided material for culture of infectious lesions, identified benign lesions not needing surgery, and aided the surgeon in planning the extent of surgery in resectable malignant neoplasms. These results support the greater use of FNA biopsy in the pediatric population.

Abdominal Neoplasms↗

Histologic spectrum of carcinomas with eccrine ductal differentiation (sweat-gland ductal carcinomas).

Seven cases of sweat-gland carcinomas showing eccrine ductal differentiation (ductal carcinomas) are presented. The tumors had a variable histological appearance, but were basically characterized by the following histological elements: (a) tubular structures, sometimes cystic or having a "tadpole" appearance; (b) solid islands of squamous, basaloid, or clear cells; (c) periodic acid-Schiff-positive endoluminal and/or intracellular material; and (d) infiltrating growth. Immunocytochemically, tumor cells were positive for keratin and negative for actin. Endoluminal material contained carcinoembryonic antigen in five of seven cases. Although it is not yet clear whether carcinomas exhibiting eccrine ductal differentiation may represent a specific histotype or a group encompassing several distinct clinicopathological entities, the histological analysis of the cases suggested that the wide spectrum of their histological appearances may be due to variable grades of differentiation.

Adenocarcinoma↗

Primary cutaneous plasmacytoma--report of two cases and review of the literature.

Primary cutaneous plasmacytomas are very rare. In this report, we describe two such cases and review the literature on this entity. Both patients presented with a slowly growing, painless, and solitary mass on the chest wall. Histologically, one case was composed of mature-looking plasma cells, while the other was composed of immature and anaplastic plasma cells, infiltrating the dermis. The epidermis was spared. Kappa light-chain restriction was demonstrated by immunohistochemical techniques in both cases. There was no evidence of marrow disease even on repeated marrow biopsies, although extracutaneous lesions were detected in one patient. One remained in complete remission 6 years following local irradiation. The other patient was treated with local irradiation and systemic chemotherapy, with a complete response, but this was followed by multiple cutaneous recurrences and further remissions by treatment with cytotoxic agents. The present cases and those reported in the literature illustrate well the variable clinical course of primary cutaneous plasmacytoma. Although cure can apparently be achieved in some patients by local radiation therapy, more than half of the cases relapse or progress to myelomatosis. The disease-related mortality is at least 40%. Thus cutaneous plasmacytoma appears to be more aggressive than noncutaneous extramedullary plasmacytomas and should be separately categorized from them in future studies.

Aged↗

Malignant lymphoma of soft tissue in an HIV-1+ patient. A rare site for primary malignant lymphoma with implications for treatment. Military Medical Consortium for the Advancement of Retroviral Research.

Soft tissue lymphomas are rare; however, the only large reported series has indicated that soft tissue lymphomas may have a better prognosis than similar-grade tumors found at other sites, and even high-grade lesions may respond to local therapies. We present a human immunodeficiency virus type 1 (HIV-1)-positive, Walter Reed stage VI black male with a documented high-grade soft tissue non-Hodgkin's lymphoma with no other evidence of tumor on complete systemic evaluation. Although extranodal lymphomas are common in HIV-1 disease, we are aware of no other reports of a soft tissue lymphoma in an HIV-1-positive patient. A significant percentage of soft tissue lymphomas in the general population, even when they are high grade, responds to local therapies including surgical excision and radiation. Thus, confirmation of this diagnosis in HIV-1 disease may be important, because these patients frequently develop fatal opportunistic infections and tolerate chemotherapy poorly, especially in late stages of disease.

AIDS-Related Opportunistic Infections↗

Malignant neoplasms associated with seborrheic keratoses. An analysis of 54 cases.

The association of malignant neoplasms arising contiguous with or adjacent to seborrheic keratoses has been previously documented. In this study a retrospective analysis was performed to further characterize these combined neoplasms. A total of 54 examples of malignant neoplasms in conjunction with seborrheic keratoses were found, of which 43 were basal cell carcinomas, six were Bowen's disease, three were keratoacanthomas, and two were malignant melanomas. The average age of the patients was over 65 years. Men were affected more frequently then women. The posterior thorax was the most common site for malignant neoplasms associated with seborrheic keratoses. The superficial type of basal cell carcinoma was the most common type of basal cell carcinoma found in this association. All subtypes of seborrheic keratosis may be found together with malignant neoplasms. We believe the appellation collision tumor is not valid because it is unknown whether the association of seborrheic keratoses with malignant neoplasms is a random event or whether there is, in fact, a pathogenic relationship in the development of two distinctive neoplasms together. Therefore, the term compound tumor is proposed to designate the finding of two distinctive neoplasms either directly contiguous with each other or immediately adjacent to each other.

Age Factors↗

Malignant proliferating trichilemmal tumor showing distant metastases.

We describe a case of malignant proliferating trichilemmal tumor showing multiple distant metastases. For 10 years, the patient had had a round mass in the occiput, which recurred twice after wide excisions, and later metastasized to the cervical lymph nodes, periparotid area, and chest. Each time the lesions were excised, histologic specimens demonstrated a proliferating trichilemmal tumor with increasing nuclear atypia. Serial specimens showed increasing Ki-67 positivity as the extent of the tumor advanced.

Adult↗

Hypersensitivity reactions to etoposide. A case report and review of the literature.

A case of immediate hypersensitivity to the chemotherapeutic agent etoposide is reported. The clinical details of the case and features of previously reported cases are outlined. An attempt to re-treat the patient with etoposide was unsuccessful despite vigorous premedication, in contrast to previous reports. The mechanism of hypersensitivity to this agent is still to be elucidated.

Adult↗

Diffuse pulmonary tumor microemboli from prostatic carcinoma with an associated fibrous histiocytic sarcoma.

Diffuse tumor microemboli to the lungs from prostatic carcinoma are extremely rare, with only six reported cases in the literature published in English. Here a seventh case is reported. The patient resembled the previously reported cases in the following ways: (1) There were minimal chest x-ray findings; (2) there was no other evidence of significant parenchymal or lymphangitic tumor involvement; and (3) pulmonary hypertension developed, but without signs of cor pulmonale. The case was even more unusual because of the presence of an apparent second neoplasm, ie, a malignant fibrous histiocytic sarcoma primary in the chest wall. There were wide-spread "collisional metastases" (metastases from each malignancy at the same site).

Adenocarcinoma↗

Localized benign and malignant fibrous tumors of the pleura. A clinicopathologic review of 223 cases.

We reviewed 223 localized fibrous tumors of the pleura and divided them histologically into 141 benign and 82 malignant neoplasms. The criteria used for a judgement of malignancy were high cellularity and mitotic activity (more than four mitotic figures per 10 high-power fields), pleomorphism, hemorrhage, and necrosis. The tumors occurred equally in both sexes, most commonly in the sixth to seventh decades of life. Presenting symptoms included chest pain, dyspnea, and cough; they were observed in three-fourths of patients with a malignant tumor. One in every four of these patients had hypoglycemia, clubbed digits, or pleural effusion. Two-thirds of the tumors were attached to visceral pleura, often by a pedicle. The rest arose from the parietal pleura of the chest wall, diaphragm, or mediastinum. Neoplasms in these atypical sites, together with fissural lesions and tumors "inverted" into peripheral lung, were more often malignant. Most neoplasms measured 5-10 cm and weighed 100-400 g. Microscopically, the "patternless pattern," or hemangiopericytic type, was seen in the majority of cases, and mixed patterns were seen in nearly 40% of tumors. Of the 169 tumors where follow-up was available, all of the benign and 45% of the malignant tumors were cured by simple excision. Patients surgically cured of a malignant neoplasm had pedunculated or well-circumscribed lesions. However, 55% of patients with malignant tumors succumbed to their disease secondary to invasion, recurrence, or metastasis. Resectability is the single most important indicator of clinical outcome. No tumor expressed epithelial differentiation, either immunohistochemically or ultrastructurally; therefore, we favor the term "localized fibrous tumor" of pleura instead of "localized mesothelioma."

Adolescent↗

Smooth muscle in atypical lipomatous tumors. A report of three cases.

Three cases of atypical lipomatous tumor with areas of smooth muscle are presented. The patients were a 49-year-old man, a 45-year-old woman, and a 63-year-old man; their neoplasms were located in the spermatic cord, the mediastinum, and the retroperitoneum, respectively. The smooth muscle foci were well differentiated in all cases. Smooth muscle was present in the primary tumor in the first and second cases (spermatic cord and mediastinum) and in a recurrence in the second case (there has been no recurrence in the first case). In the third case (retroperitoneum), smooth muscle was found only in a recurrence; it was absent from later recurrences, which showed the features of dedifferentiated liposarcoma. The smooth muscle component did not appear to influence the behavior of the tumor in any case.

Female↗

Perineurioma: an uncommon soft tissue neoplasm distinct from localized hypertrophic neuropathy and neurofibroma.

Perineurial cells, which normally surround the nerve fascicles within a nerve, can be distinguished from Schwann cells by their immunoreactivity for epithelial membrane antigen (EMA) and lack of reactivity for S-100 protein. We report two cases of perineurioma, a tumor composed exclusively of perineurial cells and distinct from other nerve sheath tumors. The first case involved a deep, soft-tissue mass of the neck, and the second involved a tumor located in the infraclavicular subcutaneous tissue. Both tumors were well circumscribed. Histologically, they were hypocellular and composed of spindle cells possessing elongated nuclei and bipolar, wavy, slender, strikingly elongated cytoplasmic processes, disposed in a background of collagen in the form of short bundles and whorls. In the first case, there were frequent calcospherites and remnants of a small nerve at the periphery. The spindle cells stained for EMA but not S-100 protein, chromogranin, neuron-specific enolase or Leu-7. Ultrastructurally, they possessed long cytoplasmic processes with incomplete basal lamina and occasional pinocytotic vesicles. Axons were not identified. Review of the literature shows that genuine perineuriomas are rare, and most cases reported as such are merely examples of localized hypertrophic neuropathy, a mononeuropathy characterized by fusiform swelling of a nerve, usually in the extremities. The involved segment in localized hypertrophic neuropathy contains distended fascicles composed of whorls of perineurial cells and fibrous tissue entrapping residual axons, probably representing a hyperplastic reaction to nerve damage. The term perineurioma should be reserved for the neoplasm composed only of perineurial cells and presenting as a soft tissue tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Reconstruction of full-thickness chest wall defects using rectus abdominis musculocutaneous flap: a report of fifteen cases.

In 15 patients chest walls were excised because of recurrent breast cancer, radiation ulcer, or rib tumor. In most cases the full-thickness defect of the chest wall was about 10 x 10 cm. Reconstruction was performed using only a rectus abdominis musculocutaneous flap. No patient developed circulation problems in the flap or severe flail chest, and we had successful results in all our cases. These results show that the rectus abdominis musculocutaneous flap is quite effective and safe to use in the reconstruction of chest wall defects.

Adult↗

Reconstruction of the chest wall with e-PTFE following major resection.

Nine patients underwent major chest wall resection at Thomas Jefferson University Hospital (Philadelphia, PA) over a 19-month period. Chest wall reconstruction was performed with an expanded polytetrafluoroethylene (e-PTFE) soft tissue patch (Gore-Tex) and vascularized flaps in all patients. The size of the skeletal defects ranged in area from 60 to 400 cm2. The primary indications for resection included chest wall sarcoma and radiation ulcer. Aggressive chest wall resection may be a patient's only opportunity for cure and an improved quality of life. In this series, chest wall resection was able to be performed with a low morbidity and no mortality. This study also demonstrates many of the advantages of e-PTFE as a chest wall substitute compared with other previously described prosthetic materials. The use of a Gore-Tex patch along with described flaps for soft tissue coverage provides good functional and aesthetic results.

Adult↗

Risks and benefits of using Marlex mesh in chest wall reconstruction.

The records of 101 patients who had undergone chest wall reconstruction both with and without stabilization of the chest wall by Marlex mesh were reviewed to see if Marlex reduced ventilator dependence and hospital stay, and to determine whether the use of Marlex was associated with any increased risk of infection. In 40 patients in whom Marlex was used, the mean number of days on postoperative ventilator support was 0.8, and mean hospital stay was 9.7 days. In 61 patients in whom Marlex was not used, the mean number of days on ventilator support was 4.9, and mean hospital stay was 17.5 days. These differences were statistically significant (p = 0.03, p = 0.006). Two patients in the Marlex-stabilized group (5%) developed wound infections, but these were preceded by ischemic necrosis of overlying flaps. None of the patients without Marlex developed wound infections. That difference was not statistically significant. We conclude that the use of Marlex in chest wall reconstruction does not significantly increase the risk of wound infection, provided that overlying tissues are properly vascularized and remain viable, and that synthetic mesh does improve chest wall stability and reduce ventilator dependence and overall hospital stay.

Adult↗