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Appendix B Clarification of Cancer Groupings Used in Reporting Results, with Correspondence to NIOSH Cause-of- Death Codes and ICD Codes for Cancers In response to a request from the Department of Veterans Affairs (VA), the committee responsible for the last report in this series (Update 2006) prepared Table B-1 to demonstrate how conclusions provided for the full range of cancer types and to clarify into which groupings any specific cancer diagnosis falls. The major portion of evidence compiled for review in the Veterans and Agent Orange (VAO) series comes from cohort studies, primarily of mortality but some of incidence. Other data have been generated by case–control studies, which fol- low the only design amenable to studying very infrequent or very specific health outcomes. How researchers are able to group, analyze, and report their findings is influenced by the distribution of cases that they observe, so the data that VAO committees have had available for review reflect mortality experience at a level of specificity concordant with statistical analysis. The International Classification of Diseases (ICD) system is used by physi- cians and researchers around the world to group related diseases and procedures so that morbidity and mortality information can be classified for statistical pur- poses in a standard form amenable to data storage and retrieval. It is a compre- hensive hierarchic system that permits great detail, but that can be collapsed into broad categories. Codes mentioned in VAO reports are stated in terms of ICD, Version 9 (ICD-9). ICD-7, ICD-8, and ICD-9 were in effect for deaths that oc- curred in 1960–1967, 1968–1978, and 1979–1998, respectively; the differences among them are fairly subtle. Although ICD-10, which went into effect for coding causes of deaths that occurred from 1999 on, appears radically different from the earlier versions, it corresponds in large part to basically the same disease entities (see Table B-2). To date, most published epidemiologic studies considered in the 666

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TABLE B-1 Mapping of Groupings of Malignant Neoplasms That Are the Subjects of Conclusions in Veterans and Agent Orange Series with ICD-9 Codes NIOSH Category for Cause of Death “VAO Characterization of Grouping”a Major Minor NIOSH Groupings of Cancer Sites Subsites ICD-9 codes 02 Buccal cavity and pharynx “Oral, nasal, and pharyngeal” 004 Lip 140 005 Tongue 141 006 Other parts of buccal cavity Salivary glands 142 Floor of mouth 144 Gum and other mouth 143, 145 007 Pharynx Oropharynx 146 Tonsil 146.0–146.2 Nasopharynx 147 Hypopharynx 148 Other buccal cavity and pharynx 149 (160 = nasal below) 03 Digestive organs and peritoneum 008 Esophagus “Esophagus” 150 009 Stomach “Stomach” 151 010 Intestine except rectum “Colorectal” Small intestine 152 Colon (large intestine) 153 011 Rectum 154 66 continued

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TABLE B-1 Continued 668 NIOSH Category for Cause of Death “VAO Characterization of Grouping”a Major Minor NIOSH Groupings of Cancer Sites Subsites ICD-9 codes 012 Biliary passages, liver, and gall bladder “Hepatobiliary” Liver and intrahepatic bile ducts 155 Gallbladder and extrahepatic bile ducts 156 013 Pancreas 157 014 Retroperitoneum and other and unspecified 158–159 digestive organs 04 Respiratory system “Respiratory” 015 Larynx “Larynx” 161 016 Trachea, bronchus, and lung “Lung” 162 Trachea 162.0 (there is no ICD 162.1) Lung and bronchus 162.2–162.9 017 Pleura 163 018 Other respiratory Nasal cavity, middle ear, and accessory sinuses (160, above with oral and pharyngeal) Thymus, heart, and mediastinum 164 (164.0, below with endocrine; 164.1, below with soft tissue sarcoma) Other respiratory, unspecified 165 (discontinuity with ICD codes) 05 019 Breast (male and female) “Breast” 174, 175 06 Female genital organs “Female reproductive” 020 Cervix uteri 180

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021 Other unspecified parts of uterus 179, 181, 182 Uterus, parts unspecified 179 Placenta 181 Body of uterus 182 022 Ovary, fallopian tube, and broad ligament 183 Ovary 183.0 (there is no ICD 183.1) Fallopian tube and other uterine adnexa 183.2–183.9 023 Other female genital organs 184 07 Male genital system 185, 186 024 Prostate “Prostate” 185 025 Testis “Testicular” 186 Penis and other male genital organs [for NIOSH in minor group 036] 187 08 Urinary system 026 Kidney (including renal pelvis and ureter) “Renal” 189.0–189.2 027 Bladder and other urinary organs “Urinary bladder” 188, 189.3–189.9 Bladder 188 Urethra, paraurethral glands, other and 189.3–189.9 unspecified urinary (discontinuity with ICD codes) 09 Other and unspecified sites 028 Bone (“and articular cartilage” in ICD “Bone and joint” 170 nomenclature) 029 Melanoma “Melanoma” 172 030 Other malignant skin neoplasm “Non-melanoma skin” 173 031 Mesothelioma No codes (new minor code, above with lung) 032 Connective (“and other soft” in ICD “Soft-tissue sarcoma” 171 nomenclature) tissue (heart) (164.1) 669 continued

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TABLE B-1 Continued 60 NIOSH Category for Cause of Death “VAO Characterization of Grouping”a Major Minor NIOSH Groupings of Cancer Sites Subsites ICD-9 codes 033 Brain and other parts of nervous system “Brain” 191–192 (ICD “soft tissue” includes peripheral nerves and autonomic nervous system) 034 Eye 190 035 Thyroid 193 (thymus) 164.0 036 Other and unspecified sites Other endocrine cancers 194 Other and ill-defined sites 195 Stated or assumed to be secondary of specified 196–198 sites Site unspecified 199 10 Lymphatic and hematopoietic tissue Lymphoma 037 Hodgkin’s disease 201 038 Non-Hodgkin’s lymphoma 200, 202 (excluding 202.4), 273.3 039 Multiple myeloma 203 (excluding 203.1) 040 Leukemia and aleukemia “Leukemia (other than chronic B-cell 204–208 leukemias)” Lymphocytic Acute lymphocytic 204.0 “Chronic lymphocytic (including hairy cell 204.1 leukemia)” Other lymphocytic 202.4; 204.2–204.9

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Myeloid (granulocytic) Acute myeloid Acute 205.0 Acute erythremia and erythroleukemia 207.0 Megakaryocytic leukemia 207.2 Chronic myeloid 205.1 Other myeloid 205.2–205.3, 205.8–205.9 Monocytic Acute monocytic 206.0 Chronic monocytic 206.1 Other monocytic 206.2–206.9 Other leukemia Other acute 208.0 Other chronic 207.1, 208.1 Aleukemic, subleukemia and “not otherwise 203.1, 207.2, 207.8, 208.2–208.9 specified” aBoldface cancer (sub)site: most comprehensive grouping for which a conclusion has been drawn. 61

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62 VETERANS AND AGENT ORANGE: UPDATE 2008 VAO series have been related to health outcomes that occurred and were encoded before ICD-10 went into effect. Since 1983, the National Institute for Occupational Safety and Health (NIOSH) has maintained software for generating standardized expectations, as derived from US mortality data assembled by the National Center for Health Sta- tistics, for ICD-encoded mortality datasets. An article by Robinson et al. (2006) discusses revisions to that standard software to incorporate deaths coded accord- ing to ICD-10 and includes conversions and equivalencies between ICD-7, -8, -9, and -10 for 119 exhaustive categories for cause of death. Codes for malignant neoplasms span the ICD-9 range 140.0–208.9, NIOSH’s major categories 02–10, or NIOSH’s more specific minor categories 004–040. The NIOSH death codes for neoplasms provide comprehensive scaffold- ing for organizing the committee’s reviews and conclusions by cancer type that is somewhat simpler than ICD classifications, but maps completely to the ICD system as it has evolved. Because the NIOSH system has been used to mediate analysis of many sets of cohort data, its groupings correspond quite closely with the published research findings available for VAO review. In general cohort stud- ies, one is unlikely to encounter results on more specific groupings than NIOSH’s minor categories. As discussed in Chapter 2, this committee has not framed its conclusions strictly in terms of ICD codes, but the ICD system has been a valuable tool for the work of VAO committees. There can be coding errors on hospital records or death certificates, but when researchers present their results labeled with ICD codes, there can be little ambiguity about what they intended. When their most definitive indication is something like “respiratory cancers,” however, there can be uncertainty about where the evidence should be considered. In such cases, the committee has done its best to follow the hierarchy laid out in Table B-1. As indicated above, many of the studies reviewed by the committee use or were written at a time when ICD-9 was in place. Accordingly, ICD references in this report use that scheme. ICD-10 began to be implemented in the United States in 1999. It differs from ICD-9 in level of detail (about 8,000 categories versus about 5,000 in ICD-9) and nomenclature (alphanumeric versus the numeric codes of ICD-9); additions and modifications were also made with regard to some coding rules and the rules for selecting an underlying cause of death (Anderson et al., 2001). Table B-2 lists the ICD-9 and ICD-10 codes for the various forms of malignant neoplasm addressed in this report. In situ neoplasms, benign neo- plasms, neoplasms of uncertain behavior, and neoplasms of unspecified behavior have separate codes in both schemes.

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6 APPENDIX B TABLE B-2 Surveillance, Epidemiology, and End Results (SEER) Program Malignant Neoplasm Site Groupings for ICD-9 and ICD-10 Cancer Site ICD-9 codes ICD-10 codes Buccal cavity and pharynx Lip 140.0–140.9 C00.0–C00.9 Tongue 141.0–141.9 C01, C02.1–C02.9 Salivary glands 142.0–142.9 C07, C08.0–C08.9 Floor of mouth 144.0–144.9 C04.0–C04.9 Gum and other mouth 143.0–143.9, 145.0–145.6, C03.0–C03.9, C05.0–C05.9, 145.8–145.9 C06.0–C06.9 Nasopharynx 147.0–147.9 C11.1–C11.9 Tonsil 146.0–146.2 C09.0–C09.9 Oropharynx 146.3–146.9 C10.1–C10.9 Hypopharynx 148.0–148.9 C12, C13.0–C13.9 Other buccal cavity and pharynx 149.0–149.9 C14.0–C14.9 Digestive system Esophagus 150.0–150.9 C15.0–C15.9 Stomach 151.0–151.9 C16.0–C16.9 Small intestine 152.0–152.9 C17.0–C17.9 Colon excluding rectum 153.0–153.9, 159.0 C18.0–C18.9, C26.0 Rectum and rectosigmoid 154.0–154.1 C19, C20 junction Anus, anal canal, and anorectum 154.2–154.3, 154.8 C21.0–C21.9 Liver and intrahepatic bile duct Liver 155.0,155.2 C22.0, C22.2–C22.4, C22.7–C22.9 Intrahepatic bile duct 155.1 C22.1 Gallbladder 156.0 C23 Other biliary 156.1–156.9 C24.0–C24.9 Pancreas 157.0–157.9 C25.0–C25.9 Retroperitoneum 158.0 C48.0 Peritoneum, omentum, and 158.8–158.9 C48.1–C48.2 mesentery Other digestive organs 159.8–159.9 C26.8–26.9, C48.8 Respiratory system Nasal cavity, middle ear, and 160.0–160.9 C30.0, C30.1, C31.0–C31.9 accessory sinuses Larynx 161.0–161.9 C32.0–C32.9 Lung and bronchus 162.2–162.9 C34.0–C34.9 Pleura 163.0–163.9 C38.4 Trachea, mediastinum, and other 162.0, 164.2–165.9 C33, C38.1–C38.3, C38.8, respiratory organs C39 Bones and joints 170.0–170.9 C40.0–C40.9, C41.0–C41.9 Soft tissue (including heart) 171.0–171.9, 164.1 C38.0, C47.0–C47.9, C49.0–C49.9 continued

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64 VETERANS AND AGENT ORANGE: UPDATE 2008 TABLE B-2 Continued Cancer Site ICD-9 codes ICD-10 codes Skin Malignant melanomas 172.0–172.9 C43.0–C43.9 Other malignant skin neoplasms 173.0–173.9 C44.0–C44.9 Breast (male and female) 174.0–174.9, 175 C50.0–C50.9 Female genital system Cervix 180.0–180.9 C53.0–C53.9 Corpus 182.0–182.1, 182.8 C54.0–C54.9 Uterus, not otherwise specified 179 C55 Ovary 183.0 C56.0–C56.9 Vagina 184.0 C52 Vulva 184.1–184.4 C51.0–C51.9 Other female genital organs 181, 183.2–183.9, 184.8, C57.0–C57.9, C58 184.9 Male genital system Prostate 185 C61 Testis 186.0–186.9 C62.0–C62.9 Penis 187.1–187.4 C60.0–C60.9 Other male genital organs 187.5–187.9 C63.0–C63.9 Urinary system Urinary bladder 188.0–188.9 C67.0–C67.9 Kidney and renal pelvis 189.0, 189.1 C64.0–C64.9, C65.0–C65.9 Ureter 189.2 C66.0–C66.9 Other urinary organs 189.3–189.4, 189.8–189.9 C68.0–C68.9 Eye and orbit 190.0–190.9 C69.0–C69.9 Brain and other nervous system Brain 191.0–191.9 C71.0–C71.9 Meninges 192.1 C70.0–C70.9 Other nervous systema 192.0, 192.2–192.9 C72.0–C72.9 Endocrine system Thyroid 193 C73 Other endocrine (including 164.0, 194.0–194.9 C37, C74.00–C74.92, thymus) C75.0–C75.9 Lymphomas Hodgkin’s disease 201.0–201.9 C81.0–81.9 Non-Hodgkin’s lymphomas 200.0–200.8, 202.0–202.2, C82.0–C82.9, C83.0–C83.9, 202.8–202.9 C84.0–C84.5, C85.0–C85.9, C96.3 Multiple myeloma 203.0, 238.6 C90.0, C90.2 Leukemias Lymphocytic Acute lymphocytic 204.0 C91.0 Chronic lymphocytic 204.1 C91.1 Other lymphocytic 202.4, 204.2–204.9 C91.2–C91.4, C91.7, C91.9

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6 APPENDIX B TABLE B-2 Continued Cancer Site ICD-9 codes ICD-10 codes Myeloid (granulocytic) Acute myeloid 205.0, 207.0, 207.2 C92.0, C92.4–C92.5, C94.0, C94.2 Chronic myeloid 205.1 C92.1 Other myeloid 205.2–205.3, 205.8–205.9 C92.2–C92.3, C92.7, C92.9 Monocytic Acute monocytic 206.0 C93.0 Chronic monocytic 206.1 C93.1 Other monocytic 206.2–206.9 C93.2, C93.7, C93.9 Other leukemia Other acute 208.0 C94.4, C94.5, C95.0 Other chronic 207.1, 208.1 C94.1, C95.1 Aleukemic, subleukemic and 203.1, 207.2, 207.8, C90.1, C91.5, C94.3, C94.7, “not otherwise specified” 208.2–208.9 C95.2, C95.7, C95.9 Miscellaneous malignant 159.1, 195.0–195.8, 196.0– C26.1, C76.0–C76.8, neoplasms 196.9, 199.0–199.1, C77.0–C77.9, C78.0–C78.8, 202.3, 202.5–202.6, C79.0–C79.8, C80, 203.8 C88.0–C88.9, C96.0–C96.2, C96.7, C96.9, C97 aCancers of the peripheral nerves and the autonomic nervous system are classified as “soft tissue” in ICD. Adapted from Ries et al. (2003), Table A-4. REFERENCES Anderson RN, Minino AM, Hoyert DL, Rosenberg HM. 2001. Comparability of cause of death be- tween ICD-9 and ICD-10: Preliminary estimates. National Vital Statistics Reports 49(2):1–32. Ries LAG, Eisner MP, Kosary CL, Hankey BF, Miller BA, Clegg L, Mariotto A, Fay MP, Feuer EJ, Edwards BK (eds). 2003. SEER Cancer Statistics Reiew, 19–2000. Bethesda, MD: National Cancer Institute. Robinson CF, Schnorr TM, Cassinelli RT, Calvert GM, Steenland K, Gersic CM, Schubauer-Berigan MK. 2006. Tenth revision US mortality rates for use with the NIOSH Life Table Analysis Sys- tem. Journal of Occupational and Enironmental Medicine 48(7):662–667.