Malignant tumors in high-altitude people

MALIGNANT TUMORS I N HIGH-ALTITUDE PEOPLE

HEVER KRUCER P., M.D., AND JAVIER ARIAS-STELLA, M.D.

N SPITE OF THE FACT THAT DURING THE LAST I 30 years Peruvian research has supplied a wealth of information concerning the physio- logical and biochemical mechanisms in the process of human adaptation to high altitudes,5 knowledge of the pathology of the high-altitude regions has made but little prog- ress. An entry into this problem has been made by certain physicians of the region, whose works have been published.’, 3, 10-12, 19, 20

In Peruvian medical circles, the idea is prev- alent that processes such as arteriosclerosis, es-

(Continued on page 1343.)

From the Department of Pathology, Facultad de Medicina “Cayetano Heredia,” Universidad Peruana de Ciencias Mkdicas y Bioldgicas, Lima, Peru.

Supported by a grant (HE-7000-03) from the U.S. Public Health Service.

Dr. Hip6lito Verastegui and Dr. Romeo Garcia provided the facilities at Cerro de Pasco, Peru.

Received for publication April 1, 1964,

FIG. 1. F.A.S., a 50-year-old Indian woman, native of Yanahuanca, altitude 11,600 feet. The malignant melanoma involves almost all of her upper lip.

FIG. 2. A, A.C., a GO-year-old Indian man, native of Yanahuanca. The bleeding tumor on the first toe of

1340 his right foot is a malignant melanoma. B, Histological section of the melanoma seen in Fig. 2‘4.

KO. 10 MALIGNANT TUMORS IN HIGH-ALTITUDE PEOPLE Kriiger 6. Arias-Stella 1341

TABLE 1 MALIGNANT NEOPLASMS IN PERSONS LIVING AT HIGH ALTITUDES

Pt. age, Anatomic yr . Birthplace Residence pathological Race Altitude Altitude Symptoms & signs Specimen diagnosis

Female fit. 52 I

50 M

52 M

52 M

28 M

48 I

50 I

50 I

52 M

56 I

8 M 68 I

63 I

Ticlacay an 11,500 ft.

Cerro de Pasco

14,300 ft.

Cerro de Pasco

14,300 f t . Cerro de

Pasco 14,300 ft. Cerro de

Pasco 14,300 f t . Cerro de

Pasco 14,300 ft. Cerro de

Pasco 14,300 f t . Cerro de

Pasco 14,300 ft.

Yanahuanca 11,600 ft.

Milpo 13,100 rt.

Cerro de Pasco

14,300 ft.

Genital bleeding, 8 mo. pregnant; polypoid tumor cervix; hypertrophy inguinal lymph nodes Genital bleeding; ulcerated cervix; rigid fornix

Genital bleeding; cervical ulcer; leukorrhea; infiltration parametrium Lumbar pain; genital bleeding; ulcerated cervical tumor; abs. fornix Hypogastric pain; genital bleeding; stony ulcerated cervix Epigastric pain; vomiting; diarrhea; anorexia; wt. loss & anemia Epigastric & rt. upp. abd. pain; a s t h e n i a ; jaundice

Blackish lesion upp. lip; hypertrophy satellite lymph nodes Tumor 1st toe It. ft.; hypertrophy inguinal lymph nodes Vomiting; fever; tumor rt. upp. abd.; anemia

Necrotic & bleeding tumor rt. eyeball Diffuse tumor rt. breast with necrosis in lower part Vaginal bleeding & tumor It . ovary

Biopsy cervix Infiltrating epidermoid ca. cervix

Cerro de Pasco

14,300 f t .

Biopsy cervix Infiltrating epidermoid ca. cervix

Infiltrating epidermoid ca. cervix



Anaplastic metast. ca. (gastric origin)

Adenoca. stomach with metast. to l iver & l y m p h nodes Malignant melanoma

Malignant me 1 an o m a

Biopsy cervix Cerro de Pasco

14,300 f t . Carhuamayo 11,530 ft.

Cerro de Pasco

14,300 f t . Cerro de

Pasco 14,300 ft . Colquij irca 13,600 ft.

Biopsy cervix

Biopsy cervix

Biopsy lymph nodes lesser curvature stomach Autopsy

Yanahuanca 11,600 f t .

Milpo 13,100 ft.

Gqyllaris- quizga 13,700 f t .

Biopsy

Amputation toe

Biopsy hepatic nodule

Enucleation eyeball

Biopsy

Metast. adenoca. gallbladder

Retinoblastoma

Infiltrating ductal ca.

Granulosa-cell ca.

Ticlacayan 11,500 ft.

Ticlacayan 11,500 ft.

Cerro de Pasco

14,300 ft.

Cerro de Pasco

14,300 ft. Tusi 11,500 f t .

Tusi 11,500 ft.

Oophorectomy

Male pt. 33 Cerro de I Pasco

14,300 f t . 58 Tangor M 11.600 ft.

Cerro de Pasco

14,300 ft. Cerro de

Pasco 14,300 ft.

Epigastric pain; melena; anorexia; anemia

Constipation ; anorexia; jaundice; ascites; ede- ma; hypoproteinemia Epigastric pain; wt. loss; anorexia; cough & high fever Bleeding tumor 1st toe rt. ft. Gen. lymph node hypertrophy; rt. pleural effus.; anFmia; hypoproteinemia Rt. cervical tumor & gen. lymph node hypertrophy Tumor with sharp bor- ders low. rt. eyelid & rt. cheek

Biopsy lymph node greater curvature stomach Biopsy liver & lymph nodes lesser curvature stomach Autopsy

Metast. adenoca. (gastric origin)

Metast. adenoca. (gastric origin)

Gastric adenoca. 50 Cerro de I Pasco

14,300 ft. 60 Yanahuanca I 11,600 ft. 62 Oroya M 12,300 ft.

Cerro de Pasco

14,300 f t . Yanahuanca 11,600 f t . Cerro de

Pasco 14,300 ft.

Cerro de Pasco

14,300 ft.

Biopsy lesion

Biopsy axillary lymph node

Malig. melanoma

Reticulum-cell sarcoma

67 Cerro de M Pasco

14,300 ft . 80 Ninacaca M 13,500 ft.

Biopsy cervical lymph node

Biopsy lesion

Reticulum-cell sarcoma

Cerro de Pasco

14,300 ft.

Basocellular ca.

1342 CANCER October 1964 Vol. 11

FIG. 3. A, S.C.R., an 8-year-old mestizo girl, native of Ticlacayan, altitude 11,500 feet. The tumor of the right eyeball is retinoblastoma. B, Histological section of the tumor in Fig. 3A.

FIG. 4. A, M.V., a 68-year-old Indian woman, native of Cerro de Pasco, altitude 14,300 feet, with a diffuse tumor of the right breast. B, Histological section of the tumor in Fig. 4A, an infiltrating ductal carcinoma.

No. 10 MALIGNANT TUMORS IN HIGH-ALTITUDE PEOPLE Kriiger Q Arias-Stella 1343

sential hypertension, and infarct of the myo- cardiums are rare or nonexistent in natives of high-altitude regions. This idea has no ade- quate scientific basis. In the same way, many speculations have been made in the past concerning the incidence of cancer in these regions.9 The studies of Mori-Chivez16-ls have conclusively shown that various kinds of ex- perimentally induced tumors develop rela- tively well in animals kept at Morococha, which is 14,900 feet above sea level. This tends to negate the idea that the physical environment of these places has any influence either in the behavior or in the incidence of malignant tumors.

In the hospitals of Lima many cases of malignant tumors have been observed in patients

~VATERIALS AND METHODS

Cerro de Pasco, where the material for this work was collected, has a stable population of approximately 20,000. Its chief industry is mining, and there is also some light farm- ing and cattle raising. The population is In- dian and mestizo. There are very few white people; these are all employees of the mining companies of the area. Medical attention is carried out in 3 hospital centers: a welfare hospital for treatment of indigents, a hospital belonging to the Cerro de Pasco Mining Cor- poration for the treatment of its workers and their families, and a Laborers’ Social Security polyclinic for the laborers of the other work centers of the region.

FIG. 5. The stomach of F.T.M., a 50-year-old Indian man, native of Cerro de Pasco. The autopsy specimen showed adenocarcinoma localized in the pyloric and prepyloric region.

who have come from the Andean regions, not a few being natives or long-term residents of high-altitude zones. However, if we attempt to make a study of these patients in the hospitals of Lima, we face serious limitations, as it would be impossible to be certain of the au- thenticity of their birthplace or length of residence in a given region.

During the last 2 years we have had the opportunity to perform autopsies and study operative specimens in the city of Cerro de Pasco, 14,300 feet above sea level, and have been able to accumulate certain information about the pathological characteristics of high- altitude residents. This paper describes several types of malignant tumors found in these people.

During 1961 and 1962 we collected 152 operative and biopsy specimens and performed 185 autopsies in both the welfare hospital and the Cerro de Pasco Mining Corporation Hos- pital. From these we gathered 20 cases of malignant tumors from Indian and mestizo patients who were natives and residents of altitudes of 11,500 feet and higher. Eighteen were obtained at operation and biopsy; 2 were obtained at autopsy. In each case a clinical history was taken, basic laboratory examina- tions were made, and standard anatomic pathological studies were performed.

TYPES OF TUMORS FOUND

Thirteen of these cases were in women:

CANCER October 1964 Vol. 17 1344

FI~: . 6. Lymph node from the stomach curvature of a 58-year-old man, native of Tangor, 11,600 feet above

FIG. 7. Liver metastases of adenocarcinoma of the gallbladder in a 56-year-old woman, a native of Goyllaris-

FIG. 8. Granulosa-cell tumor of ovary in a GS-)-ear-old woman, a native of Tusi, 11,500 feet above sea level. FIG. 9. A lymph node frotn a G5-year-old man, a na!i\e o f Cerro de Pasco, with reticulum-cell sarcoma.

sea level, showing metastatic adenocarcinoma.

quizga, 13,700 feet above sea level.

No. 10 MALIGNANT TUMORS IN HIGH-ALTITUDE PEOPLE Kriiger & Arias-Stella 1345

7 were in men. Table 1 summarizes race, place of birth and residence, principal symptoms, type of anatomic study performed, and the histological diagnosis.

I t is of interest to observe that in our series, female patients predominate over male in about 30%. This different sex incidence is attributable to the uneven hospital population, formed mainly by women (60%).

The youngest patient was an 8-year-old girl with a retinoblastoma and the oldest was an 80-year-old man with basocellular carcinoma of the face. There were 5 subjects with carcinoma of the cervix, of which the youngest was 28 years of age. Ten of the subjects were Indians; 10 were mestizos.

made using the universal nomenclature. Nine types of malignant neoplasms were identified.

DISCUSSION

In studies well controlled in regard to place of origin and residence of each subject we have conclusively shown the existence of malignant neoplasms in natives of high altitude zones of the Peruvian Andes. I t would seem to appear that variations in the physical environment, such as oxygen pressure, temperature, and de- gree of humidity, have no significant influence over this pathological process in humans.

It also seems that neither the unique an. thropological characteristics of these natives

The clinical history statements regarding the length of time the subject had had the disease varied from 14 days, in 1 case of carcinoma of the cervix, to 2 years, in a case of malignant melanoma. However, due to the low cultural and educational level of these people, initial symptoms are often disregarded or not recognized, and therefore these data should not be accepted without reserve.

The anatomic pathological diagnoses were

of extreme altitude,?, 15 nor their nutritional conditions, nor certain habits peculiar to them149 21 act to produce a susceptibility to neoplasms that is distinct from that of people adapted to and living in sea level environ- mental conditions.

Loewy and Wittkowerg have pointed out that in La Paz, Bolivia, at 11,700 feet above sea level, deaths from carcinoma are very few compared to their occurrence in zones of lower

1346 CANCER October 1964 Vol. 17

altitude. Also, Hurtado's statement4 that during his many years of work in high-altitude zones he has never observed any case of leukemia has attracted much attention. However, these declarations have been supported neither by anatomic studies nor by statistical analysis. The cases that we present here leave no doubt of the nature of the pathological process.

CPceres2 has pointed out that natives of high-altitude zones who come to be treated at the Institute of Neoplastic Diseases in Lima, show no evidence of either broncho- genic pulmonary cancer or epidermoid carcinoma of the skin. In regard to the absence of epidermoid carcinoma, it is interesting to note that one of the customs of the Andes is for the people to wear brimmed hats from the time they are young.

We, ourselves, have not observed any cases of squamous-cell carcinoma of the skin, but in this study we do present 3 cases of melano- carcinoma and 1 of basal-cell carcinoma of the skin.

Owing to the nature of our material, it is impossible for us to issue a definitive statement concerning the incidence rate of malignant neoplasms in natives and residents of high-altitude zones. Our work must be con-

sidered only as a beginning and should be followed immediately with a statistical study covering a determined sector of the native population living at high altitudes. At present we are planning a study of this kind.

SUMMARY

During the years 1961 and 1962 a study of malignant neoplasms was carried out in the city of Cerro de Pasco, Peru, altitude 14,300 feet above sea level.

One hundred fifty-two biopsy and operative specimens were collected, and 185 autopsies were performed. From these, we had 20 cases of malignant tumors in Indian and mestizo subjects who were natives and residents of areas with altitudes of 11,300 feet and higher.

The conclusion was reached that the physical environment of these zones, the unique anthropological characteristics of the natives of high-altitude zones, nutritional conditions, and certain living habits have no apparent influence over this pathological process.

The observations of several authors are dis- cussed, and the necessity of a statistical study of the pathology of the native population living in high-altitude zones is stated.

REFERENCES

1. ALVAREZ HOLLEMWEGUER, V. R.: La cardiopatia reumhtica en las grandes alturas. Thesis, Bachiller en Medicina, Universidad Nacional Mayor de San Marcos, Facultad de Medicina, Lima, Peru, 1960. Unpublished.

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gastroduodenal en las grandes aIturas (Andes peruanos). An. Fac. med. Lima 43: 419-436, 1960.

4. HURTADO, A.: Aspectos patolbgicos de la vida en las grandes alturas. An. Fuc. med. Lima 39: 957-976, 1956.

5. HURTADO, A.: Natural acclimatization to high altitudes. In CUNNINGHAM, D. J. C., and LLOYD, B. B., Eds.: The Regulation of Human Respiration. Oxford, England. Blackwell Scientific Publications. 1963; pp.

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9. LOEWY, A,, and WITTKOWER, E.: The Pathology of High Altitude Climate; with Contributions to the Climatology of Highland Regions and to the Con- stitution of High Altitude Inhabitants. London, Eng- land. Oxford University Press. 1937; pp. 40-61.

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13. MILLER, T. R., and PACK, G. T.: Familial aspect of malignant melanoma. Arch. Dermat. 86: 35-39, 1962.

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20. PEGA HERRERA, L. R.: Estudio de la ulcera gastroduodenal en un hospital de 10s Andes peruanos

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21. RONCAL, C. A: Investigacidn sobre las costurn- 22. ROSAHN, P. D.: Geographic pathology of cancer bres alimenticias en las zonas rurales del Perd; in Orient with particular reference to Thailand. In- servicio cooperativo interamericano de producci6n de

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Malignant tumors in high-altitude people