Document zQVOYeJj2bVQ8bGKmGyeaJX93

CASE STUDIES 5. Jones RR, Spaull J, Gusterson B: The histogenesis of mammary and ex tramammary Paget's disease. Histopathology 14:409-416, 1089 6. Sitakalin C, Ackerman AB: Mammary and extramammary Paget's dis ease. Am J Dermatopathol 7:335-340, 1985 7. Hamm H, Vroom TM, Czarnetzki BM: Extramammary Paget's cells: Fur ther evidence of sweat gland derivation.J Am Acad Dermatol 15:1275-1281,1986 8. Grimes OF: Extramammary Paget's disease. Surgery 45:569-574,1959 9. Oka M, Buzou S, Kenji N: Simultaneous prostate carcinoma and genital Paget's disease associated with subjacent adenocarcinoma. BrJ Urol 51:49, 1979 10. Merino MJ, Livolsi VA, Lytton B: Penile Paget's disease and prostate carcinoma. J Urol 120:121-123, 1978 11. Ikezawa Z, Ohashi Y, Nakajima H, et al: An unusual case of extramam mary Paget's disease. J Dermatol 4:19-25, 1977 12. Gudmundsen KJ, Smith JM, Dervan PA, et al: Extramammary Paget's disease and prostate adenocarcinoma. AustJ Dermatol 32:45-50, 1991 13. Tubbs RR, Sheibani K: Immunohistology of Iymphoproliferative dis orders. Semin Diagn Pathol 1:272-284,1984 14. Parikh AR, Aghazarian SG, Orbegoso CM, et al: Extramammary Paget's disease of the scrotum: Need for early biopsy South Med J 79:779-780, 1986 15. Fiorelli RL, Finkelstein LH, FernandezJL: Metastasis of prostate gland adenocarcinoma to penile and scrotal cutaneous tissue. J Am Osteopath Assoc 89:349-352, 1989 16. Venable DD, Hastings D, Misra RP: Unusual metastatic patterns of pros tate adenocarcinoma. J Urol 130:980-985, 1983 17. Marquis W, Benson R: Long-term survival with skin metastases from carcinoma of the prostate. Urology 16:407-408, 1980 18. Katske FA, Waisman J, Lupu AN: Cutaneous and subcutaneous metas tases from carcinoma of prostate. Urology 19:373-376, 1982 19. Koss LG, I^adinsky S, Brockunier A: Paget's disease of the vulva: Report of 10 cases. Obstet Gynecol 31:513-525, 1968 20. Pinkus H, Gould SE: Extramammary Paget's disease and intraepidermal carcinoma. Arch Dermatol Syph 39:479-502, 1939 21. Weiner HA: Paget's disease of the skin and its relationship to carci noma of the apocrine sweat glands. Am J Cancer 31:373-403,1937 22. Urabe A, Matsukuma A, Shimizu N, et al: Extramammary Paget's dis ease: Comparative histopathologic studies of intraductal carcinoma of the breast and apocrine adenocarcinoma. J Cutan Pathol 17:257-265, 1990 23. Mazoujian G, Pinkus GS, Haagensen DE: Extramammary Paget's dis ease: Evidence for an apocrine origin. Am J Surg Pathol 8:43-50, 1984 24. Merot Y, Mazoujian G, Pinkus G, et al: Extramammary Paget's disease of the perianal and perineal regions. Arch Dermatol 121:750-752,1985 25. Whorton CM, Patterson JB: Carcinoma of Moll's glands with extra mammary Paget's disease of. the eyelid. Cancer 8:1009-1015, 1955 26. Fligiel Z, Kaneko M: Extramammary Paget's disease of the external ear canal in association with ceruminous gland carcinoma: A case report. Cancer 36:1072-1076, 1975 27. HigashiyamaM, Doi O, KodamaK, et al: Extramammary Paget's disease of the bronchial epithelium. Arch Pathol Lab Med 115:185-188, 1991 28. TheakerJM:, Extramammary Paget's disease of the oral mucosa with in situ carcinoma of the minor salivary gland ducts. Am J Surg Pathol 12:890-895, 1988 29. de Blois GG, Patterson JW, Hunter SB: Extramammary Paget's disease arising in the knee region in association with sweat gland carcinoma. Arch Pathol Lab Med 108:713-716, 1984 30. Inada S, Kohno T, Sakai I: A case of extramammary Paget's disease of the back.jpnj Clin Dermatol 39:685-691, 1985 31. WoodruffJD: Paget's disease of the vulva; review report of two cases. Obstet Gynecol 5:175-185, 1955 32. Jacobsen JB, Haavelsrud OI: Extramammary Paget's disease: A case re port. Acta Derm Venereol (Stockh) 49:87-93, 1969 33. Jones RE, Austin C, Ackerman AB: Extramammary Paget's disease: A critical reexamination. Am J Dermatopathol 1:101-132, 1979 34. Crocker HR: Paget's disease affecting the scrotum and penis. Trans Path Soc Lond 40:187-191, 1888-1889 MALIGNANT PERITONEAL MESOTHELIOMA IN A 17-YEAR-OLD BOY WITH EVIDENCE OF PREVIOUS EXPOSURE TO CHRYSOTILE AND TREMOLITE ASBESTOS Ai.berto Andrion, MD, Sii.vano Rosia, MD, Luigi Paoletti, MD, Eeda Feyi.es, MD, Claudio Lanfranco, MD, Donata Bellis, MD, and Franco Moij.o, MD . We describe a case of malignant peritoneal mesothelioma arising in a 17-year-old boy. The diagnosis was based on a comprehensive study including light microscopy, histochemistry, immunohistochemistry, evaluation ofthe clinical course, and autopsy examination. Analytical transmission electron microscopy showed a concentration of 510,000 asbestos fibers/g dry lung tissue. The fibers were represented by chrys olite (62%) and tremolite (38%) asbestos. About. 40% of the total fibers were longer than 5 /j,m. The presence of tremolite fibers was probably due to environmental exposure to contamined cosmetic talc. 'This is the first reported case ofpathologically proven exposure to as bestos dust in malignant mesothelioma of childhood and adolescence. Hum Pathoi. 25:617--622. Copyright 1994 by W.B. Saunders Company Most malignant mesotheliomas (MMs) occur in adults, and many patients have a history of asbestos exposure with a From the Divisions of Pathological Anatomy, Occupational Med icine, and Internal Medicine, City Hospital, Asti; the Department of Ultrastructures, Istituto Superiore di Sanita, Rome; and the Depart ment of Biomedical Sciences and Oncology, Section of Pathological Anatomy, University of Turin Medical School and S. Giovanni Hos pital, Turin, Italy. Accepted for publication January 18, 1994. Supported in part by a grant from Associazione Italiana per la Ricerca sui Cancro, Milan, Italy. Key words: mesothelioma, peritoneum, childhood tumors, asbes tos, ultrastructure, immunohistochemistry, environmental pathology, cosmetic talc. Address correspondence and reprint requests to Alberto An drion, MD, Division of Pathological Anatomy, Citv Hospital, Via Bo- tallo 4, 14100 Asti, Italy. Copyright 1994 by W.B. Saunders Company 0046-8177/94/25064)014$5.00/0 ' documented latency period of two to five decades.' In the rare MMs that do occur in childhood and adolescence asbestos has not been identified as an important risk factor. Indeed, pos sible exposure is mentioned in only two instances, and the mineral was not pathologically shown in any of the studied subjects.2"1 In the present case we established the presence of chrysotile and tremolite asbestos fibers in the lung tissue of a 17-year-old boy with malignant mesothelioma of the peri toneum. CASE REPORT Clinical History A previously healthy 17-year-old boy, a nonsmoker, was referred to the City Hospital, Asti, Italy, in May 1991 with a 1month history of abdominal discomfort. On physical exami nation the abdomen was distended and tender, suggesting the presence of ascitic effusion. All laboratory investigations were within normal limits except for a slightly elevated white blood cell count with an increase in the number of eosinophils (25%). A computed tomography scan confirmed ascites, whereas all abdominal organs were normal. After paracentesis endoscopic examination showed a peritoneal cavity studded with myriads of small nodules identical to those of carcino matosis peritonei. Microscopic examination of the ascitic fluid and biopsy samples was consistent with MM. Subsequent che motherapy with vincristine, carboplatin, and epidoxorubicin was unsuccessful. The patient experienced recurrent ascites, pancytopenia, and dramatic weight loss. He died of progres sive disease 8 months after the onset of symptoms. Autopsy examination confirmed the original diagnosis of MM. 617 HUMAN PATHOLOGY Volume 25. No. 6 (June 1994) FIGURE 1. (A) Irregular spaces lined by cuboidal tumor cells are intimately associated with myxoid areas. (Hematoxylin-eosin stain; original magnification xl70.) (B) Fibrosarcomatous pattern. (Hematoxylin-eosin stain; original magnification x 170.) (C) Epithelial-like and spindle tumor cells showing keratin reac tivity. (Anti-keratin/35-Beta-Hl 1/ABC immunostain; original magnification x200.) Pathological Findings Endoscopic biopsies taken from the peritoneal nodules yielded small fragments of soft, tan to yellow-gray tissue. Mi croscopically, the tumoral specimens were composed of round to polygonal epithelial cells lining irregularly branching spaces, grouped in solid sheets, or dispersed in a prominent myxoid stroma (Fig 1, upper left). Not infrequently, fibrosarcomatous areas were seen (Fig 1, upper right). The bulk of the extracellular matrix and the cytoplasm of many epithelial cells stained with PAS and alcian blue. The reactivity was al most entirely abolished by predigestion with diastase or hyaluronidase, respectively. Sections from paraffin-embedded material were used for immunohistochemical studies. They were treated according to the avidin-biotinylated peroxidase complex procedure.4 The following series of reactions was performed: low molecular weight keratin-AEl (Biogenex, San Ramon, GA, 1:150), CEA monoclonal (Dako, Glostrup, Den mark, 1:160), Leu-Ml (Becton-Dickinson, Mountain View, CA, 618 CASE STUDIES FIGURE 3. A poorly cellular dense fibrous "desmoplastic" area of tumor. (Hematoxylin-eosin stain; original magnifica tion x 125.) 1:4), B72.3 (Biogenex, 1:160), Ber-EP4 (Dako, 1:100), HMFG2 (Serotec, Kidlingoton, UK, 1:300), smooth-muscle actin (Dako, 1:300), and vimentin (Dako, 1:150). Appropriate pos itive and negative tissue controls as well as internal controls were used. The epithelial tumoral cells together with many fibrosarcomatous elements were intensely labeled by keratin monoclonal antibody (Fig 1, bottom). Vimentin and smoothmuscle actin immunostains were positive and had the same topographic distribution within the tumor as that observed for keratin. Immunoreaction with anti-HMFG-2 antibody showed membrane staining in some epithelial and sarcomatous cells. Immunostains against CEA, Leu-Ml, B72.3, and Ber-EP4 were negative. Autopsy Findings The abdominal cavity contained 6 L of bloody stained fluid and showed multiple confluent nodules of the peritoneal surface with massive induration of the omentum (Fig 2). Ex tensive visceral adhesions with encasement of transverse, de scending, and sigmoid colon were seen. There was bilateral pleural effusion with diffuse neoplastic thickening of the pa rietal pleura on the left side. No solid organ primary site was found. The neoplastic component was microscopically iden tical to the original abdominal tumor except for the presence of fibrosarcomatous areas showing prominent desmoplasia (Fig 3). Microscopic examination of both histological sections of pulmonary tissue and sediment from digested lung failed to show asbestos bodies. Occupational and Environmental History The patient was bom and lived in a rural area (vineyard cultivation). He attended school until the age of 14. At the age of 15 he worked for 2 months in a plant that manufactured plastic tools. From the age of 16 until hospitalization he was employed as construction worker. The patient said that during this period he had only once sawed a sheet of asbestos cement using a protective mask. Among the next of kin, none had occupational exposure to asbestos. A large asbestos cement tank filled with water was present in the rural home where the boy lived. The patient's father stated that the tank water had never been used for drinking. There was no history of radia tion or drug assumption. Finally, the boy's mother remem bered that her son, from the age of 9 until about the age of 12, had a curious habit, ie, he used large quantities of cosmetic talc daily. Mineral Analysis ofLung Tissue The study of the mineral particulate extracted from lung tissue samples, according to a previously described proce dure,5 was carried out with a Philips 430 analytical transmis sion electron microscope (ATEM) equipped with an EDAX xray energy dispersion spectrometer. Fragments of lung tissue were dehydrated, weighed, and oxidized in 1 mb of atomic oxygen plasma until completely incinerated. The remaining mineral particulate matter was collected by suspension in pre filtered, particle-free deionized water. The suspension was then filtered through 0.45-^im pore-size cellulose membrane filters. The particles remaining on the filter surface were then transferred onto carbon-coated copper grids for ATEM anal ysis. The fiber concentration in the lung parenchyma was cal culated by the dry tissue weight, the total number of observed fibers, and the percentage of the analyzed membrane filter. Asbestos mineral was found at a concentration of 510,000 fibers/g of dry lung tissue. Table 1 illustrates the main char acteristics of the fiber burden in the pulmonary tissue. Sixtytwo percent of fibers were identified as chrysotile asbestos (Fig 4, upper left); the nature of these fibers was confirmed by comparing their diffraction patterns and x-ray spectrographs (Fig 4, upper right) with appropriate controls (chrysotile sam ples, National Institute for Occupational Safety and Health, USA) (Fig 5A). The other fibers (38%) showed a different morphology consistent with amphibole asbestos on the basis of their selected-area electron diffraction patterns (Fig 6). The analysis of the x-ray spectrographs of these fibers, when com pared with standard spectrographs from NIOSH tremolite samples (Fig 5B), made it possible to identify the bulk of these structures as tremolite fibers (Fig 4, bottom). In addition to asbestos fibers, many talc particles were seen with a concen tration of about 720,000/g of dry lung tissue. DISCUSSION Although the occurrence of MMs in people under 20 years of age is extremely rare and subject to high diagnostic unreliability,2,3 evidence suggests that the lesion described in this report is consistent with MM. The tumor diffusely involved the peritoneum with encasement of abdominal organs, ac companied by recurrent ascites and spreading to pleural cav ity. The histological features showed a combination of epithe lial and fibrosarcomatous elements that strongly suggested the Type of Fibers Chrysotile Tremolite Counted 26 16 Total Fibers (%) 62 38 TABLE 1. Asbestos Fibers in Lung Tissue Concentration in Dry Lung Tissue Length Mean Range Diameter Mean Range 316,000 fibers/g 194,000 fibers/g 12 /im 5 /im 1.5-20 fj.m 0.5-15 /im 0.3 0.1 /im 1-0.05 (im 1-0.01 nm 619 Fibers <5 /im 55% 70% Fibers > :i fjm 45% 30% HUMAN PATHOLOGY Volume 25, No, 6 (June 1994) FIGURE 4. Asbestos fibers extracted from lung tissue samples, (A) Transmission electron microscopic appearance of chrysotile fiber (original magnification x 16,000) and (B) the related x-ray energy-dispersive plot. (C) Transmission electron microscopic ap pearance of tremolite fiber (original magnification X8.500) and (D) the related x-ray energy-dispersive plot. A 11--OCT--S3 0 4:51:57 RRTE= 213CPS ES" 1041CNT R =cr i sot i lo NIOSH EDFlX RERDY TIME- 50LSEC F>RST~ ORE B ll-OCT-93 05:36: 10 RATE* 721CPS FS* 1041/ 10 -3 1 R e=-tr-emoli'te NIO SH SURER TIMEPRST = QUANT 50LSEC OFF FIGURE 5. X-ray energy-dispersive plots of control assays (asbestos samples provided by National Institute for Occupational Safety and Health, USA). (A) Chrysotile asbestos and (B) tremolite asbestos. 620 CASE STUDIES FIGURE 6. Selected-area electron diffraction pattern ob tained from a single fibril of presumptive tremolite asbestos fi bers detected in the lung. biphasic form of MM.6 The results of the histochemical stains, characterized by the presence of PAS-posidve diastase-sensible and alcian-positive hyaluronidase-sensible intracellular and extracellular material, were typical of MM.6 Immunohistochemical reactivity of both epithelial and fibrosarcomatous components for low molecular weight keratin, vimentin, and smooth-muscle actin; the faint reaction for HMFG-2; and lack of positivity for CEA, Leu-Ml, B72.3, and Ber-EP4 confirmed the diagnosis of MM.7'9 Finally, the length of survival from the time of the first symptoms was consistent with that reported for the biphasic type of MM.10 Childhood MM has been considered in the past to be a curiosity.11 To the best of our knowledge world literature has ' reported, to date, no more than 80 proven cases of this tu mor.2-3,12'14 In only two instances has a history of possible ex posure to asbestos been mentioned.2 On the basis of the reported figures, it has been suggested that asbestos is insig nificant as an etiologic agent of these neoplasms, and indeed factors other than asbestos, such as radiation, prenatal med ications (isoniazid), and genetic susceptibility, may be impli cated in the development of childhood MM.3 Accordingly, the reported cases of childhood MM also have been cited as evidence suggesting the existence of nonasbestos-related MM in adults.'3,16 Nevertheless, on examining most of the original papers cited by a review article2 it was seen that post mortem examination was performed in only a few cases, the light microscopic search for pulmonary asbestos bodies was sporadic, and in no case was the mineral analysis of the par ticulate extracted from lung tissue samples performed. More over, investigations of the patients' previous exposure to as bestos minerals were often superficial or even absent. In this study both the patient's history and the mineral analysis of the pulmonary tissue showed an environmental and/or paraoccupational exposure to asbestos dust. However, because asbestos fibers may be found in the lungs of the vast majority of individuals living in industrialized countries one must be exceedingly cautious in establishing a cause and effect relationship between the mineral and the disease. Although no threshold below which an individual is not at risk has, as yet, been clearly identified,117 concepts such as the "one fiber theory," which maintains that one fiber of inhaled asbestos will cause cancer, are not supported by any reasonable evi dence.18 The first question that arises relates to the evaluation of the fiber burden in the lung tissue. Appreciable variations in the analysis performance occur in different laboratories.19 It has therefore been suggested that the obtained values must be compared with the internal experience rather than with some generic standard or results from other laboratories.19,20 In the experience of our referring laboratory 84% of 85 fo rensic autopsies of subjects living in a highly polluted urban area and not affected by neoplastic diseases showed lung as bestos-fiber concentrations lower than 200,000/g dry tissue, and 16% had an asbestos burden ranging between 200,000 and 3,000,000 fibers/g.21 The overall figures were consistendy higher than those found by the same laboratory in people from remote rural areas.22 Thus, it may be argued that the lung asbestos content of our patient (510,000 fibers/g) was unusual in a rural dweller and was similar to the lung asbestos concentrations found in urban residents belonging to the sub group with the highest fiber burden.21 The second relevant question relates to the biological ef fects of different types of fibers. Accumulating evidence indi cates that chrysodle probably is not associated with the occur rence of MM at low levels of exposure,18 whereas amphiboles, including fibrous tremolite, seem to be the major causative agents of this disease.1,18,19,23'25 Moreover, most investigators believe that fibers longer than 5 fxm are the key fibers in the pathogenesis of MM.19,25 In the present case chrysotile and fibrous tremolite represented 62% and 38% of the total fibers. Structures longer than 5 /tm were found in 45% of chrysotile and 30% of tremolite fibers. This means that, on the whole, about 40% of the total burden was represented by fibers hav ing a critical length for carcinogenic potential. It is interesting to note that in the above-cited urban population21 the fiber length had a mean value of only 3 /zm and no case presented a burden of long fibers similar to that observed in our patient. The morphology of tremolite we found deserves attention be cause only x-ray spectrography was able to confirm its true nature. On. the other hand, manufacturing processes, the bio logical environment, and the laboratory procedures are all factors that may at times lead to degeneration of the "normal" fiber structure.26 Although chrysotile is used in a wide range of products present in the environment and may be considered as ubiq uitous, fibrous tremolite is a noncommercial amphibole and relatively rare from a geological point ofview. Moreover, there is wide demonstration that some types of talc may be contam inated by tremolite asbestos.27 28 Because many pulmonary talc particles were detected at the ultrastructural level the presence of tremolite was probably caused by inhaled cos metic talc. As far as the latency time is concerned, we may consider the induction period plausible. The interval between the onset of exposure and the onset of symptoms was 8 years. Little in formation is available regarding the biological effects of as bestos in young people.29 Nevertheless, MM in adults can have a latency period shorter than 10 years.30'32 Although definite proof of the asbestos-related nature of this MM cannot be established with certainty in the absence of any other documented etiologic factors, it is difficult not to 621 HUMAN PATHOLOGY Volume 25, No. 6 (June 1994) draw the conclusion that the relationship between asbestos exposure and development of MM remains the most coherent explanation of the pathological event we observed. When MMs of childhood and adolescence are diagnosed an inter disciplinary approach in which pathologist interacts with pri mary-care physicians and other specialists would be of value for a better understanding of the disease. REFERENCES 1. Craighead JE: Current pathogenetic concepts of diffuse malignant me sothelioma. Hum Pathol 18:544-557,1987 2. Fraire AE, Cooper S, Greenberg SD, et al: Mesothelioma of childhood. Cancer 62:838-847, 1988 " 3. Cooper SP, Fraire AE, Buffler PA, et al: Epidemiologic aspects of child hood mesothelioma. Pathol Immunopathol Res 8:276-286, 1989 4. Hsu SM, Raine L, Fanger H: Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: A comparison between ABC and un labelled antibody (PAP) procedures. J Histochem Cytochem 29:577-580, 1981 5. Paoletti L, Batisti D, Caiazza S, et al: Mineral particles in the lungs of subjects resident in the Rome area and not occupationally exposed to mineral dust. Environ Res 44:18-28, 1987 6. McCaughey WTE, Kannerstein M, Churg J: Tumors and Pseudotumors of the Serous Membranes. Washington, DC,`Armed Forces Institute of Pathol ogy, 1985 7. McCaughey WTE, Colby TV, Battifora H, et al: Diagnosis of diffuse ma lignant mesothelioma: Experience of a US/Canadian Mesothelioma Panel. Mod Pathol 4:342-353,1991 8. Wirth PR, Legier J, Wright GL: Immunohistochemicai evaluation of seven monoclonal antibodies for differentiation of pleural mesothelioma from lung adenocarcinoma. Cancer 67:655-662, 1991 9. Sheibani K, Esteban JM, Bailey A, et al: Immunopathologic and molec ular studies as an aid to the diagnosis of malignant mesothelioma. Hum Pathol 23:107-116,1992 10. Hillerdal G: Malignant mesothelioma 1982: Review of 4710 published cases. Br J Dis Chest 77:321-343,1983 11. Kauffman SL, Stout AP: Mesothelioma in children. Cancer 17:539-544, 1964 12. Bellocq JP, Chenard-Neu MP, Marcellin L, et al: Mesotheliome malin peritoneal chez un enfant. Arch Anat Cytol Path 37:240-247,1989 13. Geary WA, Mills SE, Frierson HF, et al: Malignant peritoneal mesothe lioma in childhood with long-term survival. Am J Clin Pathol 95:493-498,1991 14. Coffin CM, Dehner LP: Mesothelial and related neoplasms in children and adolescents: A clinicopathologic and immunohistochemicai analysis of eight cases. Pediatr Pathol 12:333-347, 1992 15. Peterson JT, jr, Greenberg SD, Buffler PA: Non-asbestos related malig nant mesothelioma: A review. Cancer 54:951-960, 1984 16. Pelnar PV: Further evidence of nonasbestos-related mesothelioma. A review of the literature. Scand j Work Environ Health 14:141-144, 1988 17. Bedrossian CWM: Asbestos-related diseases: A historical and mineral- ogic perspective. Semin Diagn Pathol 9:91-96, 1992 18. Mossman BT, Bignon J, Com M, et al: Asbestos: Scientific develop ments and implications for public policy. Science 247:294-301, 1990 19. Roggli VL: Human disease consequences of fiber exposures: A review of human lung pathology and fiber burden data. Environ Health Perspm t 88:295-303, 1990 20. Gylseth B, Churg A, Davis JMG, et al: Analysis of asbestos fibers and asbestos bodies in tissue samples from human lung: An international intei- laboratory trial. Scand J Work Environ Health 11:107-110, 1985 21. Paoletti L, Falchi M, Batisti D, et al: Mineral lung burden of an urban population. Atmosferic Environment 25B:38i-385, 1991 22. Paoletti L, Falchi M, Viviano G, et al: Features of airborne breathable particulate in a remote rural and in an urban area. Water Air Soil Pollut 43:85 94, 1989 23. Churg A, Wiggs B: Fiber size and number in workers exposed to pro cessed chrysotile asbestos, chrysotile miners, and the general population. Am J Ind Med 9:143-152,1986 ' 24. Langer AM, Nolan RP, Constantopoulos SH, et al: Association of Met- sovo lung and pleural mesothelioma with exposure with tremolite-containing whitewash. Lancet 1:965-967, 1987 ' 25. Mossman BT: Mechanisms of asbestos carcinogenesis and toxicity: The amphibole hypothesis revisited. Br J Ind Med 50:673-676,1993 26. Langer AM, Nolan RP, Addison J: Physico-chemical properties of as bestos as determinants of biological potential, In Liddell D, Miller K (eds): Mineral Fibers and Health. Boca Raton, FL, CRC Press, 1991, pp 212-225 27. Paoletti L, Caiazza S, Donelli G, et al: Evaluation by electron micros copy techniques of asbestos contamination in industrial, cosmetic, and phar maceutical talcs. Reg Toxicol Pharmacol 4:222-235, 1984 28. Gibbs AE, Pooley FD, Griffiths DM, et al: Talc pneumoconiosis: A pathologic and mineralogic study. Hum Pathol 23:1344-1354,1992 29. Kane MJ, Chahinian AP, HollandJF: Malignant mesothelioma in young adults. Cancer 65:1449-1455, 1990 30. Konetzke GW, Beck B, Herold HI: Asbestos induced mesotheliomas. Results of a retrospective study, in Prevention of Occupational Cancer. Inter national Symposium. Geneva, ILO, 1981, pp 204-212 31. Scansetti G, Mollo F, Tiberi G, et al: Pleural mesothelioma after a short interval from first exposure in the wine filter industry. Am J Ind Med 5:335-339, 1984 32. Lanphear BP, Buncher CR: Latent period for malignant mesothelioma of occupational origin. J Occup Med 34:718-721, 1992 33. Kane AB: Environmental pathology: The pathologist's responsibility? Hum Pathol 23:1093-1094,1992 CORRESPONDENCE Guidelines for Letters Letters to the Editor will be published at the dis cretion of the editor as space permits and are subject to editing and abridgement. They should be type written, double-spaced, and submitted in triplicate. They should be limited to 500 words or less and to no more than five pertinent references. Helicobacter Pylori Infection and Follicular Gastritis in Childhood To the Editor:--With reference to the article by Genta et al1 published in Human Pathology in June 1993, we have seen 122 gastric endoscopic biopsy specimens of infants and children (mean age, 3.5 + 1 years; male to female ratio, 3:1) in which gastritis was present. In 62 of the 122 cases (50.9%) it was present as a chronic superficial gastritis, in 30 cases (24.5%) as a slight chronic superficial gastritis, and in 30 cases as a slight chronic atrophic gastritis with slight activity. In these 92 cases (75.4%) Helico bacterpylori infection was not present. Only in 30 cases (24.6%) have we seen the Helicobacter infection. In seven of these 30 cases (23.3%) it was present as a follicular gastritis; the same pattern of follicular gastritis was present in 14 cases of gastritis without Helicobacter infection (15.2%; -P was not significant by the Student's West). In 20 of 30 cases with Helicobacter infection it was seen as an active inflammatory component, but this ac tivity was slight (neutrophils and eosinophils only in the lam ina propria) without erosions or ulcerations in those cases with follicular gastritis. In the cases without a follicular com ponent but with Helicobacterinfection, in 15 cases (50%) it was noted as a slight activity and in five cases (16.6%) as an erosive gastritis with moderate atrophy, whereas in three cases (10%) it was noted as a superficial gastritis. All the biopsy specimens were obtained in the antrum. In our experience the linkage between Hpylori infection and follicular gastritis has been less frequent than that de scribed by Genta et al1 in their report. There is probably less chance of chronic antigenic stimulation exerted by the micro organism during childhood. Indeed, the presence of superfi cial gastritis or slight chronic atrophic gastritis with slight ac tivity without follicular reaction shows that the H pylori in the early phases causes an acute inflammation with little epithelial damage and without a meaningful increment of the lympho- 622