‘Thickness, Cross-Sectional Areas and Depth of Invasion in the Prognosis of Cutaneous Melanoma Auexanper Brestow,* M.D. Fwom The George Washington University School of Medicine, Washington, D. C. Ceraxsous melanoma is a most unpre- dictable lesion. The marked variation in prognosis is probably a function of many variables, one of which is the size of the tumor. Though there is # roughly inverse relationship between the diameter of the Tesion and survival very small lesions have recurred or metastasized. One possible rea- son for the lack of reliability of tumor size in estimating prognosis may be that stud- {es to date have considered size in only two diamensions and have neglected tumor vol- ume. Two melanomas can have the same diameter but differ greatly in thickness be- cause of variation in either depth of in- vasion or degree of protrusion from the surface of the skin or both. A recent study * hhas shown that prognosis correlates well with staging of the depth of invasion, but there have heen no studies relating survival to tumor volume. ‘To measure tumor volume it is necessary to know the surface area of the tumor, but in this retrospective study we only know the maximal diameters of the lesions. By measuring the maximal thickness of the Te sions we can calculate the maximal cross- sectional area, which should be roughly proportional to the volume of the tumor. The depth of invasion was also studied using the criteria for staging of Clark et al Sabmitted for publication December 19, 1968 Reprint requests tn: George Washington Uni- versity’ Hospital, 901 23rd Steet, N. W,, Wash ington, D. C. 20037. 902 to sce if maximal cross-sectional area, thick: = ness, sige of invasion, or a combination of these can be of value in assessing the prog: nosis of cutaneous melanoma. A total of $8 lesions were so studied. Materials and Methods ‘The 98 patients in this study were all — free of recurrent or metastatic disease and none had satellite nodules when first seen at the George Washington University Hos: pital. None of the lesions were related ta an antecedent lentigo malignum (melanotie freckle of Hutchinson). ‘Their ages ranged from 18 to 80 (average 47). Forty-six were men and 52, women. Sixtoon had lesfons of the head or neck; 50, of an extremity; and 32, of the trunk. Following operation 71 remained free of disease for 5 or more years, while 27 de veloped metastatic or recurrent disease. Pat tients who died of unknown causes, who died im less than 5 years without melanoma and those lost to follow-up were excluded. Follow-up was 92%. ‘The maximal diameters of the lesions were measured alter fixation in Bouin's solution, Sections were taken through the center of the lesion, and slides prepared and stained with hematoxylin-eosin in the usual manner. One to five slides were pre- pared from each lesion (usually two). By means of an ocular micrometer, the maximal thickness of the Tesion. was mex sured from the skin surface to the deepest THE PF ( point of invasion. The tional area of the lesion ‘multiplying the thicknes diameter of the lesion, Stage I 1 Jasoma. Mablant had to the epiderin’s iWek, 190%). Fo. 2 Stage tt tian, The pon bed densely flame) Signet lances init the Dap dermis. but do. mot fexch the dense Te- tsar dermis H&E, iseDepth of Fi 1. Stage 1 nelinoms Malizia ned to the epidermis tire", 1908), Washington, D.C. | cross-sectional area, thick- aasion, or a combination of value in assessing the prog- 1s melanoma, A total of 98 studied. als and Methods ats in this study were all ‘or metastatic disease and te nodules when frst seen Vashington University Hos hie lesions were related to) sntir—ralignum (melanotic bins Their ages ranged average 47). Forty-six were men. Sixteen had lesions of fo Fe. 2 Stago Ut 1; 50, of an extremity; and f& ffelagoma, The papi Pt densely tnfamed tration 71 remained free of fg. Mgherantmelanosytcs timore years, while 27 de (2 Hers be BS net ttc or recurrent discase.Pa- peet=nh the dente re of unknown causes, who faimng.™ G18 ® 15 years without melanoma o follow-up were excluded. [> 9296 i I diameters of the lesions fp I after fixation in Bouin’ us were taken through the lesion, and slides prepared th hematoxylin-eosin in the One to five slides were PR Jb lesion (usually two) ‘an ocular micrometer, the {41 Point of invasion, The maximal cross-see- also staged as to the di 2 ssec- alo stage: we depth of invasion. B ves of the lesion was met foetal area of the lesion was calculated by this classification in stu lesions are stage [ Skin surface to the deepet multiplying the thickness by the maximal In stage I the tumor is confined to the ameter of the lesion. The lesions were loose papillary dermis but does not form a904 BRESLOW be. & stage nels, at sale Ae Perley eon ul eee Fis. 4, Stage IV rmelanona. Malignant ‘melanocytes inftrate the reticular dennis H&E, 250%) plaque at the junction of the loose papil- stage IV there is invasion of the reticular lary and the dense reticular dermis. In dermis, and in V, the subcutaneous fat is stage TIT the tumor forms such a plaque involved. These are illustrated in Figures and usually lls the papillary dermis, In 1-5. Fw. 5. Stage V rnelanome. Malignant ‘elanocytes infiltrate Mibeuaneous fat (1 EE, 50%). Results Tumor Size The distribution of the le to size are seen in Figures with a lesion less than 5 m less than 0.76 mm. in thickr 601 mm. in maximal cras subsequently developed rec static disease. Tumor thic nost useful measurement, i the 71 patients who remais ease. ‘The smallest _melani curred or metastasized wa 038 mm, thick with a cros of 6.16 mm. The incidence metistatic disease appears | of all three variables and w sions over 30 mm. wide or 0 and almost 1009% for lesior in maximal cross-sectional Patients whose lesions wer tim, in thickness were + those whose lesions were thick, there were no signifi jn age, sex or anatomicspots SU the Bbut on the reticalee derma tT & Fa Fic. 4, Stage JV melanoma, -Maligaant telanoeytes inftate the “retienlor dermis CH aE, 20x), ¢ is invasion of the reticular nV, the subcutaneous fat & se are illustrated in Figures cr THE PROGNOSIS OF CUTANEOUS MELANOMA Fic. 5. Stage ¥ aelanoma, Malignant telanocytes inflate Sshcutaneons fat [It E, 230%) Results Tumor Size The dtbatin ofthe Ios acon | nt F to size are seen in Figures 6-8. No patie F with a lesion less than 5 mm. in diameter, | kess than 0.76 mm, in thickness or less than [601 mm. in maximal cross-sectional area subsequently developed recurrent or meta static disease. Tumor thickness was the Stost useful measurement, identifying 38 of the 71 patients who remained free of dis “ese. The smallest melanoma which re- f cured “or metastasized was 7 mm, wide a Pee thick with a_erosssnetion’l asca _STTG mm The incidence of recurrent or Itastatic disease appears to be a function sf all three variables and was 100% for le- sions over 30 mm. wide or over 5 mm. thick aod almost 10094 for lesions over 40 mm, Fp & maximal cross-sectional area, When the. je -fstients whose lesions were less than 0.76 f™, in thickness were compared with fr those whose lesions were over 2.25 mm. thick, there were no significant differences 4 age, sex or anatomic location of the Stage of Invasion ) NUMBER OF PAnENTS Je The incidence of recurrent or metastatic disease is also a function of the stage of invasion and our findings (Table 1) are in reasonably good agreement with those of Clark et al? No stage I lesions were en- ah Latte oF oisease as Im FSCURRENCE O8 METASTASIS S59 1a 19 FOF DIAMETER (mm) 6. Diamster of melanomas. None Jess than ‘5 mm, recurred of metastasized,‘ BRESLOW sae Sem Bue Son a Mwy ue oF pisease 32. RECURRENCE OR g ‘5+ YEARS : masse ge Hil ecUMRENCE on 2 a Bu WES zg % < 3 3 ar 5 Bu 2 z. 6B. 8B BIS Pe aon Woo Eko <076 076: 150 vs 225 2236 “00 $2.00 THICKNESS. (mm Fic. 7, Maxiinal thickness of melanomas. Nope less than 0.76 nm. recurred or mstasasized 7, countered. The prognosis for stage IL tu- ‘mors is excellent with only 1 of 39 patients ping a recurrence or a metastasis devel Simultaneous Evaluation of Size and Stage In general all measurements of tumor size increased with the stage of invasion but there was a great deal of overlap (Ta- bles 2-5), For example one stage IV lesion had a maximal cross-sectional area of 6.00 mm while one stage IT lesion was 22.50 mm. in maximal cross-sectional. area. Simultaneous evaluation of tumor thick- ness_an-Staye—oF invasion Is_of greater ‘Value in assessing prognosis than i either “alone. The prognosis for stage II lesions is "Taos 1. Staging by Depth of Ineason Subsequent Recur Free of Disease ences or Metastases St Years — (umber) Number 9 1 ° oo 1 8B 4 26 rig » 6 om v 2 6 OF v 2 1 6 (CROSS SECTIONAL AREA (mn2) Fic. 8. Maximal cross-sectional area of mela: mas, Nose less than GOL im’ recured ay excellent, and the one lesion that metaste sized was over 0.76 mm, in maximal thick. ness. For patients with stage III lesions sit of 13 whose lesions were over 0.76 min, thick developed recurrence or metastases while all si of those whose lesions were = less than 0.76 mun, 5 or more years free of disease. Tumor thickness ap. ears to identify those stage II and Ill Iesions with a good prognosis, and a test of partial association in 2 x 2 tables? re veals this to be significant at the 0.05 level. By combining stage I lesions with those stage TIT lesions thinner then 0.78 mm. # group of 45 lesions is identified only one of which recurred or metastasized (2.2%). All stage IV and V lesions were thicker than 0.76 mm, survived Discussion Prognosis of cutaneous melanoma ap- pears in part to be a function of both tumor size and stage of invasion with tumor thickness the most significant measure of Stage IT lesions and lesions less that 0.76 mm. in maximal thickness are associ ated with a favorable prognosis and each ‘identified 38 of 71 patients who remained ! | THE F wise? ante 2, Measurement for St s 1 wu 1519 310 1 <076 3 151-225 226-500 0 Mae Max 2000 a : ae 5 _ Ta00 "i800 "2a 2 wa 5 7 a ‘ 1 aze1% 2 1 DSS. SECTIONAL AREA (mm?) 0 0 LS1-2.25, ¥ 3 ° f 225-300 i 3 dal crotrsectional area of mele a 4 Sito 2 3 sr tan 801 mn! tecurel & Masinal Cesssectinal am? ae {the ‘coe lesion that aici xe soa 1 ° c ? eos-t200 : : *£076 rom, nasil thick J 01 1809 i 0 201-180 i 3 rents with stage TIL lesions sx 2 1 5 1 i ts with stage IIL les ho 24 4 a 1 ! lesions were over 0.76 mm. xed —urrence or metastases of 2 whose lesions we 6 mm, survived 5 or more disease. Tumor thickness ap- atify those stage II and TI good prognosis, and a test oeiation in 2 x 2 tables re 2e significant at the 005 level 4 stage IL lesions with those ons thinner than 0.76 mm. & lesions is identified only one ured or metastasized (2.2%). and V lesions were thicker Discussion of cutaneous melanoma ap t to be a function of both stage of invasion with tumor most significant measure of lesions and lesions less tha maximal thickness are assoc: favorable prognosis and e of 71 patients who remai Sutsoquent Free of Recurrences Diese or SH Years Metastases wi i : ot a : S8 : eecnaeentes ‘Maximal Cross seetional Area & ‘Tate 5. Mfesrwemen! for Soce V Lesions Subsequent Free of Reeurtences Disese "or St Years Metastases mm Wie, <5 ° ae 3 1 1 0-18 ° “ 1510 1 1 20 0 2 ‘Thickness <076 076-150 131-235 226-300, “Maximal Cros-sectional ‘ren <601 601-1200 1201-1800, 1801-2400 >908 free of disease for 5 or more years. Only 1 stage IL lesion, 1.00 mm. thick, subse- quently metastasized. When both criteria are applied, 45 patients whose lesions were either stage IT or were stage III but thin- ner then 0.76 mm. are identifed and only 1, the thick stage II lesion subsequently metastasized. These criteria are, of course, not absolute and one can expect on occa. sion to find a lesion less than 0.76 mm. in maximal thickness which will reeur oF mé tastasize, T have seen such lesions at the National Cancer Institute, but they are rare. Patients at the Cancer Institute are highly selected, and these small lethal melanomas must represent a very small per cent of lesions operated upon These criteria may be helpful in select- ing patients for prophylactic Iymph node dissection. Though some reports. strongly advocate prophylactic node dissection whenever possible,'+* some question the value of this procedure for small super ficial lesions.*"¢ It would seem reasonable to exclude all patients with stage II lesions as well as those with stage ITI lesions thin- ner than 0.76 mm, from this procedure, Thirty-five of our 98 patients underwent prophylactic node dissection, All 12 who were in this favorable group had negative nodes including the patient with the lethal stage II lesion who died of hematogenous metastases. Summary From a retrospective study of 98 cutane- ous melanomas it was found that both tumor thickness and stage of invasion are of value in assessing prognosis, By combin- BRESLOW Vk 45 sana ot supe Reta ing these two criteria it was possible tp identify a group of 45 patients only one of ©’ whom developed recurrent or metastati disease. These criteria may be of value in selecting patients for prophylactic lymph. node dissection. 5 Acknowledgments The author wishes to thank the members of the Department of Surgery for their cooperation nd De. L. Thomas and Dr. A, Rabson of the National Institutes of Health for permission. ty examine their material. Dr. C. , Ttelind of the George Washington. University Departnent of Statistics provided the statistical analysis. Thi study would not have been posshle without the help of Mis. H, O'Brien of the George Washing. ton University Cancer Registry . References 1. Birch, M. Wy "The Detection of Partial Asa: lation, Tr ‘The 2% Cane. J. Statitt. Soo, By 26;313, 1964 2, Clark, W, HL, Ie, From, Ly Bemarding, B.& and Mibm,'M."C.- the Histogenesis tnd Be logic ‘Behavior of, Primary Human Mali = sergheagggee of te Sl, “Char ae 29:705, 1000. ; 3. Cochran’ W. Gz: Some Methods for Strength fing the Common Tests, Biometrics, 10:417, 19 met, 11 1095, 1958, 5 Kalina J. Ao ff Gros, FS. and ce W. Gi Glinizal Study of Forty-nine Patiens swith Malignant Melanoma, Cancer, 18:11, Ieee, | 6. Lehr, HB. Royster, H. P,, Entesling, H. T, ‘and Aigoritz, 8. 1 ‘The’ Surgieal. Manage: ‘ment of Patents with Melimoma. Plat, Re: constr. Surg, 40:475, 1967. | 7. Land, RH and Tinea, Ms Malignant Mela: rpoma, Chaical and Pathologie Aualvsis of 03 Cases, Surgery, 38:652, 1955, 8, Sylveny B Malignant Melanoma of the Sta, ‘Repert of “341 Cases Treated During. the 32:35, 1040 Years 1929-1048. Acta, Radiol The Anterior ¢ of Report of F Wausane F. 2 From the Deport Medicine, and \ Of Southen Tue vast majority of at surgery is performed. with complications, s0 the occasi af paralysis is often difficult though paralysis following the thoracic aorta is well d have found reports of only associated with operations + nal aorta. We have encoun tional cases. Each of the 13 syndrome of paraplegia or p ally with dissociated sensor of rectal and urinary sphine called the anterior spinal a ‘The cause is found in interf blood supply of the spinal e sible anatomic or physiologi assoeiated with the operatio Blood Supply of the S The blood supply of the derived from three to ten lumbar arteries which for median spinal artery and th spinal arteries, The anterior artery extends the length o Submitted for publication Sey * Instructor jn Surgery. °° Clinfoal Professor of Surge * Instructor in Surgery Reprint Requests: 117 F. 6th Calforoin 60813 (Dr. Max R. ¢