Sarcoidosis and Malakoplakia

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BRASHEAR AND CARMAN

serum for LE cells and virus complement fixation tests were all negative. Paul Bunnell test for heterophil antibody (not absorbed by guinea pig kidney) was positive. Pleural fluid showed many red cells and lymphocytes. Culture did not grow any pathogens, including acid-fast bacilli. Pleural fluid protein wa s 5.4 gm/l00 ml. and glucos e was 68 mg/l00 ml. Pleural biopsy showed chronic inflammatory granulation tissue only . Treatment consisted of bedrest and antibiotics, the latter be ing discontinued when the results of the Paul Bunnell test were received. The patient was discharged 36 days after admission, clinic ally well with only an occas ional atypical lymphocyte in the hlood film. Chest x-ray then showed pleural thickening on the left with peaking of the diaphragm . Serum glutamic-oxalacetic transaminase was 16 units . COMMENT

Although the initial blood picture suggested a virus infection it was not until the appearance of the palatal petechiae and the liver enlargement that infectious mononucleosis was considered as a probable diagnosis, too much importance having been attached to the reported attack of glandular fever in childhood. Diagnostic confirmation was obtained by the positive Paul Bunnell test. Wechsler and others':" reported radiologic changes in the lungs resembling those of atypical pneumonia in 14 out of 556 cases of infectious mononucleosis. Rodstein" described a patient whose condition was diagnosed as infectious mononucleosis five months after he had first presented with chest symptoms. Allen and Kellner" described the autopsy findings in an airman recently recovered from infectious mononucleosis who died shortly after a flying accident. X-ray of the chest had shown increased vascular and peribronchial markings in one lung; these changes they ascribed to mononuclear infiltration of the lung. Our patient, whose initial x-ray taken elsewhere had shown the appearance of atypical pneumonia, continued at work for seven weeks. When we met him , he presented with a pleural effusion.

Sarcoidosis and Malakoplakia* Richard E. Brashear, M.D. and Charles T . Carman. M.D.

Sarcoidosis and malakoplakia are granulomatous dis eases of obscure etiology. This is the fifth biopsy proved case of sarcoidosis and malakoplakia. The mean age was 42 years and all five cases were women, three Negroes, and in two the race was unknown. Sarcoidosis and malakoplakia have similarities and may be related.

Malakoplakia was first described by Michaelis Cutmann! in 1902 and named by von Hansemann- in 1903. It is an uncommon granulomatous inflammation usually involving the urinary bladde and occurrring predominantly in women. Microscopically, the lesions consist of a granulomatous infiltrate with inflammatory cellular elements, mononuclear ceIls and calcospherites (Michaelis-Cut mann bodies). The etiology and pathogenesis is obscure." Approximately 120 cases of malakoplakia have been reported.':" Sarcoidosis is also a granulomatous disease of obscure etiology that has never been histologically proved to involve the urinary bladder.":" This is a report, with a review of the literature, of the fifth proved case of sarcoidosis and °From the Departments of Med icine , Indiana University Medical Center, Indianapolis, Indiana, and University 0 California Medical Center, San Francisco, California. Supported in part by research grants HE-06228, HE 04080, Program Project Grant HE-06308, and Postgraduate Research Training Grant 5363, all from the National Heart In stitute, USPHS, and in part by USAF contract AF 33(615)2922.

I am indebted to Dr. V. U. Lutwyche, under whom the patient was ad mitted , for her interest a~d advice, to Dr.!. M. Tuck. for the report on the pleural biopsy and to Dr. D. S. Carmichael for hematological investigations. ACK!':OWLEDG~IE!':T:

REFERENCES

WECHSLER, H.F., ROSE:".~LU"( , A.H ., A:"."D SILLS, C.T .: Infectious mononucleosis: Report of an epidemic in an army post, Ann. Int. Med ., 25:113. 1946. 2 RODSTEI:", ~1.: A case of infectious mononucleosis with atypical pneumonia, Ann . Int . Med., 28:1177 , 1948. .'3 ALLE:", F.H ., JR., A:"."D KELL:"ER, A.: Infectious mononucleosi s: An autopsy report, Amer. J. Path., 23:463, 1947. Reprint requests : Dr . Sarkar, 106/2 Kali Kundu Lane, Howrah I, We st Bengal, India

I

FIGURE 1. Chest roentgenogram demonstrating a large right: paratracheal lymph node and enlargement of both hilar areas, (August, 1959).

DIS. CHEST, VOL. 56. NO.4, OCTOBER 1969

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361

malakoplakia occurring in the same patient. CASE REPORT

The patient, a 47-year-old Negro woman, was first adnutted to the University of California Medical Center on August 3, 1959, with the chief complaint of hematuria for one year . She had been well until one year prior to admission when she noted the onset of dysuria, urgency, terminal hematuria and nocturia. Past history included a hysterectomy in 1952 and a bowel resection in 1954 because of adhesions. Physical examination showed obesity, a blood pressure of 140/70 and normal pulse and respiration. The remainder of the examination was norma\. Urine was grossly bloody with pH 6.5, 2+ protein and many white blood cells. Urine smear showed gram negative rods and culture grew Escherichia coli. Creatinine was 1.4 mj:(/I00 ml, hematocrit .'34 percent and white blood cell count 7,200/mm:l . Intravenous pyelogram demonstrated filling defects in the bladder and a right ureterocele. Chest roentgenogram (Fig 1) disclosed bilateral hilar enlargement and a 2.5 X 5 cm right paratracheal node . Cystoscopy showed elevated and nonulcerated lesions of the bladder and a biopsy (Fig 3, 4) ernonstrated malakoplakia consisting of a proliferative granulomatous inflammation with chronic and acute inflammatory cells and Michaelis-Gutmann bodies. She was lischarged August l.'3, 1959 on regimen of antibiotics. After discharge her urinary symptoms improved slightly ut the urine continued to be loaded with red blood cells. n September 1.5, 1959, she was evaluated in the chest linic because of bilateral hilar enlargement and the right aratracheal node noted on the previous roentgenogram (Fig 1). There were no pulmonary symptoms. Serum calcium as 10..'3 mg/100 ml, Total serum protein was 7.6 j:(m/l00 I and electrophoresis showed gamma glohulin increased o 29 percent (N 16.1 percent ± 4.0 percent) of the total rotein. A 2.5 X 1 cm moveable right supraclavicular mass as found and excised October 12, 1959 . This supraclavicular

IGURE 2. Chest roentgenogram demonstrating no change in he right paratracheal node and hilar areas . There are now aint nodular and linear densities in both lower lung fields, April, 1962) .

DIS. CHEST, VOL. 56 , NO.4, OCTOBER 1969

FIGCRE 3. Urinary bladder showing thin transitional epithelium at upper left and a polymorphous inflammatory infiltrate, hematoxylin and eosin, X 160.

lymph node (Fig 5) showed numerous foci of epithelioid cells with marked vacuolization. Lymphocytes were scattered around these granulomas. 1\0 caseation was evident and the reticulin stain demonstrated that strands of reticulum coursed uninterruptedly through the granulomas. The results of Ziehl-Neelsen acid-fast stain, Comori's methenamine silver stain and Congo red amyloid stain were all negative. This was compatible with sarcoidosis. Unfortunately, no skin tests were performed at this time. The dysuria, hematuria and frequency continued and on February 2, 1960, she was started on prednisone 25 mg daily. On February 16, this dose was reduced to 20 mg daily and then stopped on April 12. The urinary symptoms increased despite the prednisone. The patient was admitted the second time on April 26, 1960, because of progressive urinary symptoms. Physical examination was unchanged . Urine was loaded with whit!" and red blood cells and culture grew E. coli, creatinine was 1.2 mg/l00 m\. Intravenous pyelogram showed bladder defects and the chest roentgenogram was essentially unchanged. Cystoscopy showed diffuse involvement and a repeat bladder hiopsy on April 22, 1960, was unchanged showing granulomatous inflammation and Michaelis-Gutmann bodies of malakoplakia. She was discharged April 26, 1960. During the next 20 months she continued having dysuria, hematuria, and frequency and the urine remained loaded with red and white blood cells and gram negative rods . On January 26, 1962, prednisone 30 mg daily was resumed because of a progressive finely nodular infiltrate involving both lower lung fields. The hilar adenopathy was unchanged . There were no chest symptoms. Prednisone was

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plakia has usually occurred in women (80 percent) and most frequently in the urinary hladder.4.7·:!CI.:!1 Sarcoidosis occurred in women in 40 percent of 951 patients" and ha s never been histologically proved to involve the urinarv bladder, N.!! The two diseases can involve renal parenchyma,":" Both sarcoidosis and malakoplakia have inclusion I bodies. The Schaumann bodies occur predominantly : in sarcoidosis but are also found in tuherculosis and I berylliosis, They are 25 to 40 microns and lamellat ed or conchoid in appearance. Schaumann hod- I ies consist of a primary, inorganic, highly hirefringent, .intracellular crystal nidus, probably calcite. This may he surrounded by a secondary calcium impregnat ed prote in-complex concho id hody.22 Mich nclis- .utmann bodi e (cnlco: ph crit es ) are cY- 1 toplasrnic inclu sions about 1 to 10 microns and ar I cha ractcri: tic of malakopl akia. Th es hodie. are oval or round and tar get -shap ed . Th e centra l portion is I compo. ed of an acid mu copolysaccharide and lipids; protein . iron and ca lcium arc deposited in layers aro und this nu cleu s.' Temer and Lattes tat e that Michaelis- ,utman n hodi e arc compo. eel of a special glycolipid that is probablv the etiologic agent of malak opl ak ia. H Knoop ' > dcscrib d as typ ical for hoth sa rcoido . is and malakopl akia the e pithelioid II

I

FIl;U1u: 4. Urinary bladder showing a infiltrate composed of lymphocytes, neutrophils, large mononucleated cells, and a typical ovoid Michaelis-Cutmaun body in the center, hematoxylin and eosin , X 480 .

reduced to 20 mg daily aft er two weeks and continued at 10 mg daily aft er April 24, 1962 . The chest roentgenogram remain ed unchanged (Fig 2) . During the next seven months, the urinary complaints continued unchanged and she dev eloped a urethral polyp at the meatus. Steroids apparently had produced no improvement. She was scheduled for ad mission to th e hospital November, 1962 , hut she failed to return. DISCUSSION

Table 1 summarizes the cases of sarcoidosis and malakoplakia proved by biopsylo.t:I Smith" and French and Mason!' stated that Redewill'" reported two cases of sarcoidosis and malakoplakia. However, only the second case of Redewill'? had hoth sarcoidosis and malakoplakia. Smith" also mentioned a woman who developed sarcoidosis "several years" after the diagnosis of malakoplakia was estahlished. No comment was made about a biopsy or histology and this case is not included in Table 1. Melicow.' Cederqvist" and Temer and Lattes''" referred to cases reported by Morison!" and Hagemann. 16.i r However, careful review of these three original papers,I;; .17 disclosed no case of sarcoidosis and malakoplakia occurring in the same individual. Multiple etiologies have been suggested for hoth surcoidosis'v-!" and rnalakoplakia.v-P" However, the etiology of each disease remains obscure. Mal ako-

FIGPIU; 5. Lymph node demonstrating granulomatous foci without caseation. See text for furth er description hematoxylin and eosin. x 40 .

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363

5ARCOIDOSIS AND MALAKOPLAKIA Table I-Proven Cases of Sarcoidosis and Malakoplakia Age , Sex

Urinary Bladder

1943

40 F Race ?

French, Masonl ! 1951

Negro

Malakoplakia, biopsy at cystoscopy Malakoplakla, hiopsyat cystoscopy

Knoop t 2 1958

46F Race ?

Malakoplakia, hiopsyat cystoscopy

Curtis et aJl :l 1961

Negro

34F

Malakoplakia,

47 F Negro

cystoscopy Malakoplakia, h iopsy at cystoscopy

Reference

Redewill!"

41 F

Present case

biopsy at

elusions, spontaneous improvement, elevated amma globulin, and low tuberculin sensitivity. edewill!" also descrihed similarities hut McKiel nd associates-" failed to find any relationship beeen malakoplakia and sarcoidosis. Mayock and o-workers" described two cases of sarcoidosis with ematuria and related this to unrecognized renal tones . It is possible that the hematuria could have een a manifestation of malakoplakia. It is sugested that any patient with sarcoidosis who has ematuria, pyuria, or urinary symptoms be romptly given a cytoscopic examination for the ossibility of concurrent malakoplakia. Patients with alakoplakia should be carefully studied for saroidosis. It must also be remembered that. hoth disases may be asymptomatic. Again, the question rises about the possihility that sarcoidosis and alakoplakia may be related and malakoplakia may present the sarcoid tissue response of the urinary ladder. The authors wish to express their at itude to Carry L. Bolinger. M.D., for his assistance with I.' tissu e sections and pathologic interpretation.

CKi\OWLEDG~fEi\T:

REFEHENCES

MICHAELIs, L., A:"iD GUTMANN, C. : Ueber einschlusse in blasentumoren, Z . Klin . Med., 47 :208, 1902. vox HAXSE~IAXX: Uber malakoplakie der hamblase. Virchow . Arch . Path . Anat., 173 :302, 1903. PESSI:"i, S.B., A:"iD ASIlEI\SOS, W .A.D .: Lower urinary tract and male genitalia, in AXDERSOX, W .A.D., (ed .) Pathology, C . V. Mosby, Co ., Saint Louis, 1966 . MELICOW, M.M.: Malacoplakia : report of case , review of literature. J. Urol., 78 :.'33, 1957 . S~I1TH, B.H.: Malacoplakia of the urinary tract: a study of 24 cases, Am er. J. Clin . Path ., 43 :409 , 1965 . CEDERQVIST, L.L. : Malacoplakia of the urinary tract: a theory of pathogenesis, Arch . Path . 80 :495, 1965 . YUNIS, E.J .. ESTEVEZ, J.M ., 11:-'"2ox. C .J., A:-''U MORAX, T .] .: Malacoplakia: discussion of pathogenesis and report of three cases including one of fatal gastric and colonic

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Sarcoidosis

Treatment

Cutaneous lesions Biopsy of skin

Not reported

Cutaneous lesions Biopsy of skin Abnormal chest roentgenogram Right scalene lymph node biopsy Abnormal chest roentgenogram Biopsy eyelid Ahnormal che st roentgenogram Biopsy right supraclavicular lymph nod e Abnormal chest roentgenogram

Sulamyd and calcium with some improvement Steroids and antibiotics with improvement INH, SM, PAS with improvement Steroids and antihiotics without improvement

involvement, Arch. Path ., 83 :180, 1967 . 8 MAYOCK, R.L., BERTRASD, P., MORRISOX, C .E .. A:"iD SCOTT, J.H .: Manifestations of sarcoidosis : analysis of 145 patients, with a review of nine series selected from the literature, Amer. J. Med., 35 :67 , 1963 . 9 MCGOWAN, JR., A.J., AXD SMITH, E .H .: Urological implications of sarcoidosis, J. Urol., 97 :1090, 1967 . 10 REDEwILL, F .H .: Malakoplakia of the urinary bladder and generalized sarcoidosis, striking similarity of their pathology, etiology, gross appearance and methods of treatment, J. Urol., 49:401, 1943 . 11 FHE:'\CH, J.A .. A:'\D Mxsox, J.T. : Malakoplakia of urinary bladder and sarcoidosis, J. Urol., 66 :229, 1951. 12 Kxoor-, R. : Malakoplakia; oversigt og beskrivelse af det forste tilfaeldge i Danmark, Ugeskr. Laeu., 120:498, 1958 . 13 CURTIS, \V.R., BozzELL, J .D ., A:-''U CREE:'\, C .L.: Malacoplakia of bladder: report of a case successfully tre ated with antituberculosis medical therapy, J. Urol., 86 :78, 1961. 14 TERXER, J.Y., A:>.'U LATTES, R.: Malakoplakia of colon and retroperitoneum : report of a ease with histochemical study of the Michaelis-Gutmann inclusion bodies, Amer. J. Clin . Path., 44 :20 , 1965. 1.'5 MORISO:,\, J .E. : Malakoplakia of the urinary bladder, J. Path . Bact ., 56 :67, 1944 . 16 HAGEMAXX, E .: Kasuistischer beitrag zur sogenannten malakoplakie der hamblase, Z. 44 :9, 1951. 17 HAGE~IAX:'\, E .: Zur sogenannten malakoplakie der hamblase , Z. Ural., 45 :45, 1952. 18 Proceedings of the Third Intemational Conference on Sarcoidosis, Stockholm, September 11-14, 1963, Acta Med. Scand. , 176 (Stipp. 42.'5):1, 1964 . 19 SILTZBACH, L.E. : Current thoughts on the epidemiology and etiology of sarcoidosis, Amer. l . Med., 39 :361 , 196.'5 . 20 McKIEL, JR., C .F ., EISE:'\STEIS, R., A:-''U McDoxALD, J.H .: Morphological and rnicrobiologtcal studies in malacoplakia, J. Urol., 88:236, 1962 . 21 BEXXETT, \V.H .: Malacoplakia of the urinary tract: report of three cases, t. Urol., 70 :84, 1953. 22 WILLIA~IS, W .J.: The nature and origin of Schaumann bodies, J. Path . Bact ., 79 :193, 1960.

o-«,

Reprint requests: Dr. Brashear, Indiana University, Indianapolis 46202