American Journal of Hematology W:167-169 (1982)

Second Malignancies in Hairy Cell Leukemia (Leukemic Reticuloendotheliosis) David J. Stewart and Michael J. Keating

The Department of Developmental Therapeutics, The University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, Houston

Key words: associated malignancies, hairy cell leukemia, radiation exposure

INTRODUCTION

It is not uncommon for patients who have had one malignancy to subsequently develop another one [ 11. Although scattered cases have been reported of associated ma- lignancies in patients with hairy cell leukemia (HCL) [2-61, the extent of the association is unknown.

We reviewed the charts of all 31 patients with HCL (all male) seen at M.D. An- derson Hospital and Tumor Institute from 1973 to 1979. Median age was 49 (range: 23-64 years). Median follow-up from detection of a hematological abnormality was 8 years (range: 5-15 years).

Four of the 3 1 (- 13%) patients had deeply invasive or metastatic-associated malig- nancies diagnosed either before or after detection of their hematological abnormality.

Case 1

A 49-year-old male developed lymphadenopathy and splenomegaly in 1973 and pancytopenia in Septemer 1974. In May 1977, a diagnosis of HCL was made. In Febru- ary 1978, a malignant fibrohistiocytoma was removed from the left eyebrow. In Febru- ary 1979, adenocarcinoma of the stomach was diagnosed by gastroscopic biopsy. He died 1 week later. At autopsy a linitis plastica carcinoma of the stomach and a benign thyroid adenoma and residual hairy cell leukemia were found. At age 23, while in the A i r Force, the patient had been hospitalized for apparent radiation sickness following exposure to an atomic bomb test explosion. The number of rads to which he had been exposed is unknown.

Received for publication March 13, 1982; accepted April 24, 1982.

Address reprint requests to David James Stewart, M.D., Ontario Cancer Foundation, Ottawa General Hospital, 501 Srnyth Road, Ottawa, Ontario KIG 8L6, Canada.

0361-8609/82/1302-0167SO1.50 0 1982 Alan R. Liss. Inc.

168 Brief Report: Stewart and Keating

Case 2

A 44-year-old man developed increased fatigability in December 1975. Hepato- splenomegaly and anemia were noted in March 1976. Splenectomy and open liver biop- sy were performed in April 1976, and a diagnosis of HCL was made based on histo- pathological studies. In 1969 he had had an invasive basosquamous carcinoma of the left inguinal region treated by surgical resection. Recurrences were excised in 1971 and 1972. At the time of the second recurrence, deep extension along blood vessels was noted. Radiotherapy (6,000 rad) was administered to the area following the second re- currence, 4 years prior to diagnosis of HCL.

Case 3

A 42-year-old psychoanalyst had worked extensively in his father’s dental office developing X rays in his youth and did a 2-month diagnostic radiology rotation during his internship. In 1961 he had a papillary carcinoma of the thyroid resected. In 1964 and 1965 he was noted to have granulocytosis. Over the next several years, he gradually developed persistent granulocytopenia and lymphocytosis. Atypical lymphocytes were noted in 1969, and a diagnosis of HCL was made in 1979.

Case 4

A 49-year-old male was noted to be pancytopenic at the time of diagnosis of a Mycobucteriurn kunsusii infection in 197 1. Antituberculous medications eradicated the infection, and halotestin was initiated because of the pancytopenia. In March 1976 the patient underwent excision of a squamous cell carcinoma of the skin from the right pre- auricular area. Extension had occurred into the parotid gland. Radical neck dissection revealed no metastatic disease in the cervical lymph nodes. However, lymph nodes and bone marrow were extensively replaced by HCL. In March 1977 metastases from the squamous cell carcinoma were found in axillary lymph nodes.

In Bouroncle et al’s series of 26 patients with HCL, they reported 1 patient who developed colon carcinoma 6 years following the diagnosis of HCL [2]. Burke et a1 [3] had 1 out of 21 HCL patients who was found to have metastatic squamous cell car- cinoma of the lung 5 years following the diagnosis of HCL. In a series of 12 HCL pa- tients Plenderleith [4] reported l patient with a basal cell carcinoma and l patient who was pancytopenic at the time of diagnosis of adenocarcinoma of the prostate, was treated with diethylstilbestrol, and was later diagnosed as having HCL. Schnitzer and Kass [5] reported 1 patient who developed a squamous cell carcinoma of the lower lip in 1951 followed by one in the nasal area in 1971. Shortly thereafter, she was found to have HCL. Friedman and Covey [6] reported a 72-year-old lady found to have HCL 12 years after treatment of a liposarcoma by surgery and nitrogen mustard.

We have previously noted that radiation exposure may be an important etiologi- cal factor in some cases of HCL and that the incidence of thyroid abnormalities (pos- sibly radiation induced) is increased in HCL [7]. It is notable that radiation exposure occurred in three of four HCL patients with deeply invasive or metastatic-associated malignancies. In addition, another HCL patient had acne irradiated 35 years prior to the diagnosis of HCL and currently has a large cold thyroid nodule but refuses surgery. We feel that the coexistence of two malignancies in our three HCL patients with a his- tory of radiation exposure may have been due to radiation exposure precipitating one

Brief Report: Second Malignancies in HCL 169

or both of the malignancies. Exposure to both low and high doses of irradiation may re!;ult in the development of a variety of malignant diseases [8,9]. It is less likely, but possible, that an immune defect associated with HCL may precede a detectable hema- tological defect and may predispose to the development of an associated malignancy.

ACKNOWLEDGMENTS

We would like to thank Dr. C.C. Shullenberger for allowing us to review the charts of patients with hairy cell leukemia who were being followed by the Department of Medicine at M.D. Anderson Hospital.

This work was supported in part by Grant CA-10376 from the National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

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