Squamous Cell Carcinoma of the Anus in a Patient with Chronic Lymphocytic Leukemia
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CASE IN POINT SQUAMOUS CELL CARCINOMA OF THE ANUS IN A PATIENT WITH CHRONIC LYMPHOCYTIC LEUKEMIA Wen S. Lai, MD and Jonathan E. Dowell, MD Many studies suggest a link between this type of leukemia and the development of additional primary malignancies, but an association with anal cancer has been largely overlooked. he idea that patients with pletely understood, it’s believed for three years and had become leukemia may be pre- that immunosuppression inherent constant over the past two months. disposed to developing in CLL may play a key role. Here, His medical history was notable T additional primary malig- we present the first detailed case only for low risk, Rai stage 0 CLL nancies was first suggested in 1878, report of a patient with CLL who that had been found incidentally at when Whipman reported a case of developed squamous cell carci- another hospital seven years earlier pancreatic cancer in a patient with noma of the anus. This case sug- and had never required treatment. underlying leukemia.1 Since then, gests that the risk of anal cancer, as On physical examination, the pa- numerous publications have sup- with other types of malignancies, tient had no palpable lymphade- ported the association between may be increased in patients with nopathy and no evidence of liver or leukemia and other malignancies, CLL and further implicates abnor- spleen enlargement. Digital rectal particularly in patients with mal immune function as the proba- examination revealed a firm mass chronic lymphocytic leukemia (CLL). ble cause of the propensity toward along the left wall of the anal canal Although the pathogenetic additional malignancies associated approximately 3 to 4 cm from the mechanism for this link is not com- with a CLL diagnosis. anal verge. A complete blood count revealed an elevated white blood INITIAL EXAM cell count of 76 x 103/µL (normal, 4 Dr. Lai is a staff physician in the general internal A 77-year-old man presented to the to 11 x 103/µL), a low hemoglobin medicine department and Dr. Dowell is the chief of the hematology and oncology department, both at Dallas VA Medical Center, Dallas, level of 10.6 g/dL (normal, 13 to the Dallas VA Medical Center, Dallas, TX. In addi- TX reporting rectal pain during 17.3 g/dL), and a normal platelet tion, Dr. Lai and Dr. Dowell are both assistant pro- defecation and streaks of bright red count of 2.3 x 105/µL. A white blood fessors in the internal medicine department at the University of Texas Southwestern Medical Center at blood on the stool. These symp- cell differential showed 99% Dallas. toms had occurred intermittently lymphocytes and 1% neutrophils Continued on page 60 58 • FEDERAL PRACTITIONER • JANUARY 2005 CASE IN POINT Continued from page 58 (normal, 37% to 80% neutrophils Given that CLL is relatively com- nosis, could result in an increased and 20% to 45% lymphocytes). mon and typically affects elders, it detection of additional malignan- Peripheral blood immunopheno- might seem reasonable to dismiss cies. If this were the case, however, typing demonstrated a distinct pop- an association between CLL and one would expect that most of the ulation of lymphocytes comprising additional primary cancers as co- second malignancies would be dis- approximately 95% of the sample incidental. Yet convincing epide- covered around the time of CLL di- cells. Consistent with a diagnosis of miologic data link CLL with agnosis. Yet both SEER reviews B cell CLL, these cells expressed subsequent malignancies. Two found that the heightened cancer CD5, CD19, CD20, and CD23 glyco- large reviews of the National risk was constant across all time in- proteins and failed to express CD10. Cancer Institute’s Surveillance, tervals after CLL was diagnosed,3,4 Colonoscopy confirmed the Epidemiology, and End Results suggesting that ascertainment bias presence of a 3-cm fungating mass (SEER) database found an elevated is not a significant contributor to along the left wall of the anal ca- risk of second cancers—specifi- this phenomenon. nal. Biopsies revealed squamous cally, lung cancer, malignant A second possibility is that a cell carcinoma. A computed tomog- melanoma, brain tumors, soft tis- common genetic or environmental raphy scan of the abdomen and sue sarcomas, and Hodgkin’s dis- factor predisposes patients to both pelvis showed no pathologically ease—in patients with CLL.3,4 In CLL and the additional malignancy. enlarged lymphadenopathy or addition, a number of reports sug- After review of the SEER data on other evidence of metastatic gest that squamous cell carcinoma neoplasms associated with CLL, disease. of the skin, which is not included in however, Greene and colleagues the SEER database, also occurs found no elevated risk of any type TREATMENT COURSE more frequently when CLL is pres- of leukemia following the diagnosis The patient’s anal mass was treated ent.4–10 Case reports of gastric of these tumors.3 The association, with concurrent chemotherapy cancer,11 Merkel cell tumor,12 ade- therefore, appears to be one-way, (cisplatin and 5-flurouracil) and ra- nocarcinoma of the esophagus,13 which argues against a common diation therapy, which resulted in a and small-cell carcinoma of the etiology for both tumors. Greene complete tumor response. Three colon14 also have been published. and colleagues also point out that months after the completion of Ours is the first detailed case re- their finding suggests that a CLL- therapy, he remained disease free. port of a patient with CLL who de- associated “susceptibility state” veloped squamous cell carcinoma may result in the development of ABOUT THE CONDITION of the anus. Two earlier series, pub- additional primary malignancies. CLL—which is characterized by lished in 1965 and 1987, each re- The susceptibility state that has the clonal proliferation and accu- ported on a patient with CLL and been implicated most often for the mulation of neoplastic B lympho- anal cancer but did not provide increased risk of second cancers cytes in the blood, bone marrow, specifics of the cases (including associated with CLL is abnormal lymph nodes, and spleen—is histology).7,10 Anal carcinoma is immune function. It’s possible that the most frequently diagnosed quite uncommon, representing only drugs used to treat CLL might play leukemia in Western countries. 0.003% of all cancer diagnoses.15 a role in this, but the data at pres- Classically, it is diagnosed in pa- Given this extremely low inci- ent are uncertain. In a 1990 report, tients in their sixties and has a male dence, it’s not surprising that the the French Cooperative Group on predominance. Due to the in- SEER reviews did not detect an in- Chronic Lymphocytic Leukemia creased frequency of blood count creased risk of anal cancer in pa- demonstrated a higher incidence of orders in recent years, approxi- tients with CLL. epithelial cancer among patients mately 60% of CLL diagnoses today What’s behind this increased with early stage, low risk CLL who are made when patients are asymp- risk of malignant disease in pa- were randomly assigned to receive tomatic. Prognosis for patients di- tients with CLL? Several hypothe- indefinite treatment with chloram- agnosed with CLL is variable, with ses have been proposed. First, it’s bucil 0.1 mg/kg/day (33 of 303 pa- some having a normal life span, been suggested that ascertainment tients, or 11%) than among those while others die within five years bias, as a result of the medical at- who were randomly assigned to of diagnosis.2 tention that comes with CLL diag- receive no treatment (19 of 309 60 • FEDERAL PRACTITIONER • JANUARY 2005 CASE IN POINT patients, or 6%).16 The authors, recurrent bacterial and atypical It’s at least plausible that similar however, did not define the statisti- infections and autoimmune phe- immunologic incompetence, as a cal significance of this finding. nomena.2 consequence of CLL, led to the de- Anecdotally, neither our patient Furthermore, the pattern of sec- velopment of anal cancer in our nor many of those with second ma- ond primary cancers observed in patient. One fact that argues lignancies reported in other small CLL is similar to that seen in pa- against our supposition, is the lack series ever had received treatment tients receiving chronic immuno- of a clear link between CLL and for their CLL. Furthermore, neither suppressive therapy following cervical cancer, which has a similar of the two large SEER reviews renal transplantation. Specifically, pathogenesis to anal cancer.3,4 demonstrated a clear association the frequencies of lung cancer, Even so, it seems reasonable, over- between CLL treatment and the malignant melanoma, and squa- all, to conclude that patients with risk of a second malignancy.3,4 But mous cell carcinoma of the skin are CLL may be at increased risk for virtually all of the data for these re- increased in both populations.19,20 anal cancer. ● views were accumulated before the In addition, it has been observed nucleoside analogues were com- that squamous cell carcinomas of The opinions expressed herein are monly employed in CLL, and these the skin far outnumber basal cell those of the authors and do not drugs are well known to possess carcinomas in patients with necessarily reflect those of Federal immunosuppressive effects. In fact, CLL and in those who’ve under- Practitioner, Quadrant HealthCom a case report published in 1997 gone renal transplantation—but Inc., the U.S. government, or any of its agencies. This article may discuss unlabeled or investiga- tional use of certain drugs. Please Until more definitive data become available, review complete prescribing infor- mation for specific drugs or drug we cannot assume that CLL treatment plays combinations—including indica- tions, contraindications, warn- more than a modest role in the increased risk ings, and adverse effects—before administering pharmacologic of second cancers.