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References 1. Amador E: Normal ranges, Progress in Clinical Pathology. Vol 5. Edited by M Stefanini. New York, Grune and Stratton, 1973, pp 59-83

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2. Casey AE, Downey E: Further use of statens in the recording, reporting, analysis and retrieval of automated computerized laboratory data. Am J Clin Pathol 53:748-754, 1970 3. David HA: Order Statistics. New York, John Wiley and Sons, Inc., 1970, pp 66-67 4. Elveback LR: How high is high? A proposed alternative to the normal range. Mayo Clin Proc 47:93-97, 1972 5. Elveback L: The population of healthy persons as a source of reference information. Hum Pathol 4:9-16, 1973 6. Elveback LR, Taylor WF: Statistical methods of estimating percentiles. Ann NY Acad Sci 161:538-548, 1969 7. Feinstein AR: Clinical biostatistics. XXVII. The derangements of the "range of normal." Clin Pharmacol Ther 15:528-540, 1974 8. Grasbeck R: " N o r m a l " and "reference" values for laboratory data. Lancet 1:244-245, 1976 9. Herrera L: The precision of percentiles in establishing normal limits in medicine. J Lab Clin Med 52:34-42, 1958 10. Lennox B: Normalisation: A possible general solution to the units problem. Lancet 2:1085-1086, 1975 11. Lo JS, Kellen JA, Moore RW: Expressing results of laboratory tests. Clin Chem 22:1759-1760, 1976 12. Mainland D: Remarks on clinical " n o r m s . " Clin Chem 17: 267-274, 1971 13. Reed AH, Henry RJ, Mason WB: Influence of statistical method used on the resulting estimate of normal range. Clin Chem 17:275-284, 1971 14. Reed AH, Wu GT: Evaluation of a transformation method for estimation of normal range. Clin Chem 20:576-581, 1974 15. Rossing RG, Hatcher WE: Estimation of percentiles in laboratory data, Proceedings of the 16th San Diego Biomedical Symposium. Edited by Jl Martin. New York, Academic Press, 1976, pp 459-463 16. Rossing RG, Hatcher WE: A computer program for estimation of reference percentile values in laboratory data. Computer Programs in Biomedicine 9:69-74, 1979. 17. Sunderman FW Jr: Current concepts of "normal values," "reference values," and "discrimination values" in clinical chemistry. Clin Chem 21:1873-1877, 1975 18. Thompson WR: Biological applications of normal range and associated significance tests in ignorance of original distribution forms. Ann Math Stat 9:281-287, 1938 19. Werner M, Marsh WL: Normal values: Theoretical and practical aspects. CRC Crit Rev Clin Lab Sci 5:81-100, 1975 20. Wright BM: Normal = 10 ± 2. Lancet 2:1261, 1975

Lymphatic Invasion in Pigmented Nevi MARTHA EMMA ADELINE BELL, M.D., DONALD PATRICK HILL, M.D., AND M. KRISHNA BHARGAVA, M.D.

Bell, Martha Emma Adeline, Hill, Donald Patrick, and Bhargava, M. Krishna: Lymphatic invasion in pigmented nevi. Am J Clin Pathol 72: 9 7 - 1 0 0 , 1979. All 124 pigmented nevi registered at the Canadian Tumour Reference Centre between

Canadian Tumour Reference Centre, Department of Pathology, University of Ottawa, Ottawa, Ontario, Canada

Received April 25, 1978; received revised manuscript and accepted for publication August 31, 1978. Presented at the Canadian Congress of Laboratory Medicine, June 1977, Hamilton, Ontario, Canada. Address reprint requests to Dr. Bell: Canadian Tumour Reference Center, Department of Pathology, University of Ottawa, Ottawa KIN 9A9, Ontario, Canada.

July 1958 and May 1969 were reviewed. Nevus cells invading endothelial lined spaces were observed in serial sections from five cases. The significance of this finding is discussed in relation to published reports of the presence of nevus cells in lymph nodes. (Key words: Pigmented nevus; Lymphatics; Metastasis.)

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although not normally distributed, do not manifest extreme degrees of skewness or kurtosis, and linearization by the probability transformation would be expected to be satisfactory. The two methods of estimating percentiles discussed in this paper have been compared as to their performances on simulated data.16 The regression method was shown to have a negligible bias and to provide estimates more stable and less variable than those obtained by interpolation. This, in addition to the convenience of obtaining all desired percentile equivalents from a single procedure, makes the regression method advantageous. We have now incorporated the method presented for estimation of percentiles into the computer programs that analyze our clinical spirometric tests. We routinely report to the clinician not only the observed and predicted values in conventional units of volume or flow, but the corresponding percentile value as well. An example of such a report is seen in Figure 5. This subject has values that are clearly normal for forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV,), and maximum mid-expiratory flow rate (MMEF). However, his values for flow rates when 30 and 20% of his vital capacity remain to be expelled (V30 and V20) would be considered borderline and would merit further investigation. This fact is brought more clearly to the attention of the clinician by the percentile values than would be the case had we reported only the predicted and observed values.

BELL, HILL AND BHARGAVA

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FIG. 2 (lower). Case 2. Large nevus cells appear to form part of the wall of a lymphatic and a few cells appear to lie within the lumen. Hematoxylin and eosin. x250.

IN 1931, Stewart and Copeland9 found nevus cells in the hilar connective tissue of an axillary lymph node in a patient with neurofibromatosis, malignant melanoma, and a large bathing-trunk nevus. Since then a total of 46 instances of nevus cell aggregates in lymph nodes from Table I. Summary of Five Cases

Case

Patient's Sex, Age (Years)

Site of Nevus

1 (CTRC 13149)

F, 5

Conjunctiva

2 3 4 5

M,45 F, 29 F, 22 F, 42

Skin, back Skin, ear Skin, back Skin

(CTRC (CTRC (CTRC (CTRC 1

6390) 4470) 4239) 6729)

NER indicates no evidence of recurrence.

Follow-up Recurrence excised at 2 years NER* 8 years NER 16 years NER 4 years Lost to follow-up NER 16 years

axilla, neck or groin have been reported.7 McCarthy and associates,5 in 1974, surveyed all lymph-node resections for cutaneous, thoracic and abdominal lesions over a two-year period. They found nevus cells in 6.2% of axillary nodes. The pathogenesis of this phenomenon is unclear. "Benign metastasis" from cutaneous nevi wasfirstsuggested by von Albertini.10 Since one of us (D.P.H.) had observed a close relationship between nevus cells and vascular spaces, we studied our cases of benign nevi to obtain evidence to substantiate this theory. Materials and Methods From July 1958 to May 1969, 124 benign pigmented nevi were submitted as diagnostic problems to the Canadian Tumour Reference Centre for consultation. These were categorized as 46 compound nevi, 22 intra-

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FIG. 1 (upper). Case 1. Subendothelial hillocks of nevus cells in one lymphatic with two apparent free clusters of nevus cells in an adjacent lymphatic, suggestive of emboli. There are numerous scattered lymphocytes. Hematoxylin and eosin. x 100.

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FIG. 3 {upper). Case 3. Polypoid masses of nevus cells containing melanin project into the lumen of a lymphatic in subcutaneous fat. Nevus cells, rather than endothelial cells, form the wall at the base of these polyps. Hematoxylin and eosin. x250.

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BRIEF SCIENTIFIC REPORTS Vol. 72 • No. 1 References 1. Amador E: Normal ranges, Progress in Clinical Pathology. Vol 5. Edited by M Stefanini. New Yo...
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