HUMAN PATHOLOGY Volume 22, No. 6 [June 1991) CRISIS IN SICKLE CELL TRAIT ALDEN W. DUDLEY, JR, MD, AND CAROIAE;E CL WADDEI,L, MD A ;3+yea?--old bluck male with hemoglobin AS was admitted for renal failure, polvdipsia. h@vtension, .schizophrenia. mental confusion, and visual hallucinations. Abnormal electrolytes were corrected by dialysis, but blood specimens were reported-a.5 hemolvzed with hvperkalemia. Peaked T UV~~~Q.T on electr-ocardiographic analysis wbre follozoed by cardiac arr&. An auto@ revealed sickled cells in the visual cojtex and other symptomatic organs. but normal erythrocyte.s in most of the vascular tr-ee. These findings sugge.rt true popes&e sickle cell crisis in a hemoglobin AS patient. Hr ‘M P,4nlol, 22.616418. This is a US government work. T~QT-Q arp no restricfiorL< on ils USQ. malities. Because the density of’ the A and S bands was typical of sickle cell trait (approximately 60%~/40%~), studies for thalassemia were not performed. The level of glucose6-phosphate dehydrogenase was tested and found to be normal. Hematology consultation was not requested; test results were considered irrelevant to the patient’s illness. Upon admission. the patient described visual hallucinations without paranoid ideation. He could not stand up because his legs became shaky and he had a severe intention tremor. All four extremities were restrained. Because of the serum sodium of I 17 mg/dL, fluid intake was restricted to 1,200 ml, dailv. Bv the third hospital day he became increasingly coni‘used, occasionally “violent,” and lay staring a~ the ceilinp. Hemodlalysis was performed on januar!; 26. 1987; the blood sample received by the laboratory was reported as “hemolyzed” (‘Table 1). Subsequent samples were also hemol,yzed and showed rapidly climbing potassium (despite sodmm polystyrene sutfonate therapy), uric acid, aspartate aminotransferase, and lactate dehydrogenase levels. concurrent with falling hematocrit, hemoglobin, platelet count, albumin, and globulin levels. An EKG showed peaked -1‘ waves, tachyca;dia, and left bundle branch block. On January 27, 1987, he had a generalized tonic-clonic seizure and suffered cardiac arrest at 1:15 AM, was resuscitated briefly, and finally pronouncecl dead at 5:OO AM. Fully 8% of black Americans carry hemoglobin AS (hgb AS) and are described as having sickle cell trait (SCT) -an “innocuous” genotype. ’ Several investigators have described symptoms and death which they attributed to a sickle cell crisis in patients with hgb AS.“-a However. others have questioned these reports because of “undue reliance on postmortem findings of’ intravascular sickling” without supportive laboratory data.rl Failure to anticipate a diagnosis of sickle cell crisis in this patient precluded a full spectrum of laboratory tests OI hematology consultation. However, there remain sufficient laboratory, electrocardiographic (EKG), clinical, and autopsy features to be pathognomonic for a sickle cell crisis. Sickled cells were restricted to symptomatic organs and regions of the brain. These findings support the hy!>othesis that patients with hgb AS may develop a sickle crlsls undelphysiologic duress (hypoxia, acidosis, or dehydration). CLINICAL An aurops~ re\ealed intimal thickening throughout large medium-sized renal arteries in kidneys weighing only 75 g each. Glomeruli were severely atrophic. The heart weighed 625 g, hacl complete pericardial fibrosis, and showed concentric thickenin of both ventricles without scars. The lungs had a combmed weight of 1.705 g, were deeply congested, and edematous with mild anthracosis. Whereas IIIOSI pulmonary vessels had normal erythrocytes, some peripheral small vessels contained sickled cells. The gastr+$mostomy was open and adequate. Mucosal vessels were normal, but submucosal venules were often filled with sickled cells. The liver weighed 1,900 g, had a tense capsule, and irregular areas of mottled yellow or dark red-brown. Microscopy of‘the liver revealed thrombosis, infarction. and necrosis alternating with congestion and hemorrhage, a pattern characteristic of disseminated intravascular coagulation. All red cells in the infarcted areas. and most in the congested or hemorrhagic sites, were sickled. The spleen weighed 250 g, was tense. densely packed with sickled red cells, and several splenic veins contained hemosiderin and red cell-laden macrophages. It had siderosis reflecting excessive chronic destruction of erythrocytes. The bone marrow was grossly hyperemic, had 70% cellularity, and showed a particular increase in erythroid precursors, including normoblasts. The thymus revealed extramedullary hematopoiesis. Sickled red cells were found in selected vessels of the kidneys and testes as well. The fresh brain weighed 1,500 g, was extremely pale. and had unif’ormly mildly swollen gyri without herniation of the uncus or tonsils. The ventricles were mildly reduced in volume but there were no grossly discernible lesions in gray or white matter. Luxol Fast blue-periodic acid-Schiff stains revealed multiple sites of ischemic malacia. with the largest fcjcus 4 by 1 mm in the left occipital watershed zone of white matter. Arterioles to these sites were plugged with HISTORE’ A 34-year-old black male with paranoid schizophrenia, progressive dementia, hypertension, and end-stage renal disease was hospitalized January 23, 1987 for visual hallucinations and tremors of 3 days’ duration. Past history included surgery for right facial and abdominal stab wounds in 1967. In 1981, the patient was first noted to be hypertensive. By 1983, blood pressure was 2141158 mm Hg with grade 3 fundus. In March 1984, blood urea nitrogen level was 126 mg/dL (4.5 mmol/L) and creatinine level was 18.7 mg/dL (1,650 pmol/L). The patient was given an arteriovenous access graft for triweekly hemodialysis. He was a thin man who frequently drank entire quarts of water. After 1984, the patient had multiple hospitalizations for acute psychosis with auditory hallucinations and paranoia. A bleeding peptic ulcer was treated by gastrojejunostomy in March 1986. In May 1986, a screening Sickledex test was positive and hemoglobin showed hgb A and S without other abnor- Received from the Departments of Pathology and Medicine, Veterans Administration Medical Center. Houston. TX; and Baylor College of Medicine, Houston, TX. Accepted for publication August 27. 19’90. Key waraL: sickle cell trait, sickle crisis, autopsy. dialysis, hyperkalemia, stroke. Address correspondence and reprint requests to Alden W. Dudley. Jr, MD, Veterans Administration Medical Center (1 13). 2002 Holcombe Blvd. Houston, TN 77030. This is a US government work. There are no restrictions on its use. 0046-8 177/9 l/2206-00 18$0.00/O 616 CASE STUDIES TABLE 1. Serum Hematology and Chemistry IkIt< IIL’lIHi l!“: not the case. ‘l‘he selec.ti\v tlistl-iftution in our patient of cickliug ant1 siderosis irl ;iw,ts wilti infarction is serrntlipicou9. Occipital arteriole plugged with degenerating sickled FIGURE 1. red blood cells and with perivascular red cell and hemosiderinladen macrophages. (Luxol Fast blue-periodic acid-Schiff stain: magnification < 1,000.) FIGURE 2. Neighboring patent arteriole with nonsickled intraluminal erythrocytes. (Luxol Fast blue-periodic acid-Schiff stain; magnification P 1.000.) 617 HUMAN PATHOLOGY Volume 22. No. 6 (June 1991) sies on XT patients with L’2 ( 18%) showittg massive sickling and cerebral infhrcts. 1.3 (13%) having massive sickling of cerebral vessels withour proven infitrcts. and the remaining 83 (69%) containing multiple vessels with sickled cells but no impactions. Thus , 30% of. S(ZpI‘patients had signiticant sickling and may have had central net-votes system symp totns. Patients with SCJ‘ have had slow, progressive infarction of‘ the ftraiti and sf)irtaf cod,"? f>ituitnr!;. and retina.“’ Hemoglobin AS is ttot an innocuous ~enotvpe. Karl\ et al’ 1 have recentfv shown 2111 increased itt&len& of’ sucfdett death in SCT re&tits. High altitude encatnpn~et~t, exercise, and flying without comf)ressiott are acceflted causes of sickling in heterozygous disease. Many military personnel are exposed to all three of‘ cite above hazards. The visual hallucinations without paranoid ideation were a cfue to sickling. The cerebraf comf~ottettt of’ sickle cell anemia and Xl‘ cntphasi03 bilateral watershed areas with sluggish circulation (relative hyf”)f’et.fitsiott), stagttaCon, and the potential for sickling. Subcortical white tnatter in the occipital pole is most frequently involved,” and is the most logical site for \,isual hallucinations of’ organic origin. Frontal pole, centrum ovalr, internal capsule, and potts follow in descending order of‘ fl-ecfuency as sites of’ isc-ltemia and infarction. The laboratory ref’ort of “hrtiiol~sis” of’ tfte hfood was reasonable in view of‘ elevated serum l~o~assiutii level and pigmentation. However. it wax not due to f’ftfehr)tottt);, ~rallSpOr~ }mddeiilS. 01‘ hr:lliIlg of’ the bhd. .h’ sickle CTsis led to apparettt disseminated intravasculat. coa,gulatiott. and infarction of multiple organs (liver, spleen, etc.) c-ausecl fysing of their cells. Repeat blood santpfes showed progressive elevation of‘ serum potassiunt tt) 7.5 mg!dL., the E:I(<; 1‘ wave spiked, and the patient died. Treatment OK sickle cell crisis is both physiologic and symptomatic. Bicarbonate. tratisf’usiott with hgh AA hfood hypotonic saline (up to three to four liters). and hyfjet-baric oxygen are recommended.’ Curiousf~. intravenolts fluids may actually flush enough red cells f’rc~tn caf,iflaries to raise the ltetttatocrit level.‘” Routine high intake of water is a strong f~rophyfactic as well as therapeutic regimen for sickle cell anemia or %:‘I‘. OSTEOCLAST-LIKE GlANT CELL TUMOR OF THE PANCREAS: IMMUNOPHENOTYPIC TUMOR OF BONE SIMIIARITY TO GlANT CELL reported for now& us teoclrcs t.r 7’hrJi,ldings .\upport a nonepitheliccl origin /tir rJsteoc&,+like giant cell tumor of the puncr-eas, and .srqpgest CLderiwtion .rimilu,- to girtnt cell tumor of bone. Hc ;II P.~UIOI. 22.6 18-622. Copyright 0 1991 by W.B. Saunders Corn- An imrnunophenotype ws perfurmrd on an ostrocla~t-like giclnt cell tumor of the pancreus using a panel oJ antibodirv to epitheliul and leukocyte antigens. Sezjerul antibodies to cytokerutin end carcinoembryonic untigen were negative in the lumor. Osteoclu.+like crll,\ were positizle for CD-#, CD13, CD+5, CD68, CD71, and zherltin, but negatizjefor lysozyme and HI,A-DR. Mononuclear tumor cells were positizle for CDJ, CD1 lc, CDI?, CDI4, CD15. CD68, CD71, HLA-DK, and zlimentin, but negutive /or ly.s.roqww. TOP phenotype is similar to that prez&u.sly described for giant cell humor of bone. The o.~teo&st-like cell phbrrot@c is ulso similur to that pi ‘l_$ Osteocfast-like giant cell tumor of’ the pancreas (OG’I‘P) is an ut~usual entity originally.described by Rosai,’ and characterized by osteoclast-like giant cells and ntononuclear stromaf cells identical to those seen in giant cell tumor of bone. It is distinct f’rom the pleontorphic giant cell tumor of‘ the fjattcreas, Jacking the marked nuclear pleomorphism associated with that entity. Often ;I histologically recognizable pancreatic carcinoma accompanies OG’TP, and the majority of the 15 previously reported case? have favored att epithelial origin for the giant cells. We report a case of’ OGTP with immurtohistochemical characterization of the tumot- using a panel of antibodies to leukocyte and epitheliaf antigens. ‘f‘he findings indicate that the imntunophenotype of OC;I‘P resembles that of giant cell tumor of bone, and suggest a nonepitheliaf origin for the tumor. From the Departments ot Pathology and SIJI-get-y, University of Chicago. Chicago. IL. Accepted for ptlblication September 17, 1990. Key urorcitr giant cell tumor, osteoclast, irtnnunoct~zynte techniques. pancreatic rteoplasms. leukocyte antigens. Address cot-respondence and reprint requests to Anthony (;. Montag, MD. University of Chicago. Box 27-1, .5X+1 S Mar&tnd Ave. Chicago. IL 60637. Copyright 6 IWI by W.B. Saunders Cornpan\ 0046-X 177/91/1206-(JO IY$Fi.OOIO 618