CASE REPORT

Scand J Haematol(l978) 21, 104-108

Lymphomatoid Granulomatosis of the Lung, Liver and Spleen

s. A. sCHJ0LSETH & G. P.BLQM University of Trams(, Medical Department and Department of Pathology, Tromsl, Norway A female patient with lymphomatoid granulomatosis (LYG) involving lung, liver and spleen is described. Our case presented with signs and laboratory data indicating severe hepatic failure. It is not clear if this disorder represents a distinct pathological or clinical entity. In this report the differences between LYG and the two disease groups which it most resembles, Wegener’s granulomatosis and malignant lymphoma are discussed.

Key words: liver failure - lymphomatoid granulomatosis

Accepted for publication April 7, 1978 Correspondence to: G. P. Blom, M.D., Department of Pathology, University Hospital, N-9012 T r o m b , Norway

Lymphomatoid granulomatosis (LYG) was described by Liebow et a1 (1972) as an angio-destructive, lymphoreticular proliferative and granulomatous disorder with polymorphous cellular infiltrates, containing lymphocytes, plasma cells and atypical mononuclear cells exhibiting varying numbers of mitoses. There is predominantly involvement of the lungs, but lesions may also be seen in other organs, especially the kidneys, nervous system and skin. The renal lesions are similar to the nodular masses within the lungs, unlike the focal glomerulonephritis of classical Wegener’s granulomatosis. In contrast to malignant lymphoma, the spleen and lymph nodes are seldom affected. However, in 5 of the

40 originally reported cases, the disease progressed to atypical lymphoma with involvement of lymph nodes and other reticuloendothelial tissues (Liebow et a1 1972). The clinical manifestations in early LYG are rather nonspecific such as fever, malaise, weight loss, dyspnoe and productive cough, occasionally also haemoptysis. Radiographically the pulmonary lesions are predominantly in the lower lobes of the lung, usually bilateral, resembling metastases. Routine laboratory investigations and immunological studies have not contributed to the diagnosis since alterations so far have been few and minor. A definite diagnosis can be made only if an adequate biopsy is obtained. Thoracotomy is in-

LYMPHOMATOID GRANULOMATOSIS

dicated (Lee et a1 1976). The prognosis of LYG is poor. Corticosteroids appear to have induced remissions in some cases, but the effect of cytotoxic therapy has not yet been proved (Saldana et a1 1977). Liebow et a1 (1972) suggest that immunological deficiency may be a factor in the pathogenesis of the disease, and a recent report confirms the development of LYG in an immunosuppressed renal transplant recipient (Hammar & Mennemeyer 1976). CASE REPORT The patient was a 55-year-old female who previously had been in good health. At the end of Sept 1976 she was hospitalized with a 5-week history of fever, weight loss and lassitude. Physical examination revealed jaundice, moderate dyspnea and a temp. of 39O C. Chest x-ray showed bilateral nodular densities involving predominantly the lower zones (Figure 1). Laboratory findings: Urine analysis was normal except for bilirubinuria. ESR (Westergren 1 h) = 6 mm. H b 12.1 g/dl. WBC 2.2 x 109/1, and platelets 54 x

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1W1. Liver function tests were abnormal throughout hospitalization. At the time of admission liver function tests were: Bilirubin 123 pmoyl, alkaline phopshatase 889 U/l, gamma-GT 2700 U/1, ALAT 311 U/1, ASAT 247 UA and LDH 920 U/1. The results of the same tests on the day the patient died were 438 pmoYI, 2134 U/1, 473 U/1, 155 U/1, 207 U/l and 1250 U/1, respectively. Although serum albumine was only 27.2 g per 1, normotest was within normal limits. Immunoelectrophoresis revealed normal levels of IgG, IgM and IgA. Tests for rheumatoid factor, antinuclear factor, antimitochondrial antibody and antismooth muscle antibody were all negative. Liver biopsy (Menghini) showed portal infiltrates of lymphocytes and monocytoid cells with some nuclear atypia. Bronchoscopy was unremarkable and sputum cultures for acid-fast bacilli were negative. A bone marrow biopsy was normal. Course in hospital. On admission treatment with high dosage i.v. penicillin was started without effect. 2 d later, because of the possibility of miliary tuberculosis, penicillin was discontinued and antituberculous chemotherapy was begun. Simultaneously high dosage prednisolone (40-80 mg/d) was administered for a possible col-

Figure 1. Chest roentgenogram revealed multiple nodular opacities throughout the lung, more numerous in the basis. Hila normal.

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lagenosis. On this regimen there was a rapid fall in temp., some regression of jaundice and of the bilateral pulmonary nodulation, and an improvement in general condition. However, 2 weeks later the patient’s condition deteriorated, with return of fever and progression of jaundice and of the pulmonary densities. In spite of antibiotic and corticosteroid therapy she died on Oct 31, approximately 3 months after the first symptoms were observed.

ment. The liver, wt. 1720 g, was soft, yellow, and had multiple greyish-white, irregular but well-demarcated infiltrates up to 1.5 cm in diameter. The spleen weighed 450 g and showed several well-demarcated lesions macroscopically suggestive of infarcts. No macroscopic changes were found in the heart, kidneys, bone marrow or brain. There were no cutaneous lesions.

AUTOPSY

Gross findings The lungs, wt. 1370 g, were diffusely infiltrated with small white nodules up to 5 mm in diameter, especially in the periphery of the lower lobes. There was no hilar, mediastinal or other lymph node enlarge-

Microscopic findings The lung nodules were areas of coagulation necrosis surrounded by a sparse mononuclear infiltrate. Most prominent was a vasocentric and vasodestructive inflammatory process affecting both veins and smaller

Figure 2. Pulmonary vein with a mixed mononuclear infiltrate containing some atypical cells.

LYMPHOMATOID GRANULOMATOSIS

arteries in the vicinity of the necrotic areas (Figure 2). The infiltrate was dominated by lymphocytes with some plasma cells and some large, atypical, mononuclear plasmacytoid cells with scanty cytoplasm and large, bizarre nuclei showing some mitoses. No Reed-Sternberg cells were seen. The bronchial wall was not affected. The spleen was hypocellular and congested. Otherwise the process was the same as that in the lungs, with areas of coagulation necrosis and nearby vessel walls infiltrated by mononuclear cells with some larger, atypical cells. The liver lesions were found principally to affect the portal tracts. In some areas no changes were seen. Otherwise the portal tracts showed variable infiltration by mono-

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nuclear cells. In the most affected areas the infiltrates were dominated by the large, atypical cells (Figure 3), expanding to produce macroscopic lesions. Some mitoses were seen. The vessel walls and also the bile ducts were clearly infiltrated. The bone marrow was unremarkable. Unfortunately, only two small retroperitoneal lymph nodes were examined, and these were normal. In the brain, a few very small perivascular lymphocytic infiltrates were seen in the pons and in the meninges. No atypical cells were found. The kidneys were normal. DlSCUSSION

At autopsy the patient presented with infarcts in the lungs and spleen, and an ex-

Figure 3. Liver infiltrate showing a preponderance of large, bizarre cells. Some degenerating hepate cytes are seen.

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tensive hepatic affection. Microscopic ex- variegated infiltrate and the lack of Reedamination revealed an angiocentric and Sternberg cells serve to separate LYG from angiodestructive chronical inflammatory lymphoma. process in the three organs, exhibiting Except from jaundice, this patient proliferative bizarre mononuclear cells con- presented with non-specific symptoms as sistent with LYG. Angiitis with infarct-like is usual in early LYG. There was no evinecrosis in the spleen has been reported in dence of skin lesions, nor of central or Wegener’s granulomatosis (Spencer 1969), peripheral nervous system involvement but not in cases presented as LYG. Spleno- which in LYG are reported to occur in megaly caused by congestion is relatively 45 % and 35 % of the cases, respectively common in LYG and was present in this (Liebow et a1 1972). Corticosteroids have case. The hepatic involvement was of the reversed the disease process in some pasame kind as the pulmonary and splenic tients (Liebow 1973, Lee et a1 1976, Salprocess. There was a patchy portal tract dana et a1 1977). In our case, corticosteroid infiltrate affecting vessels and bile ducts, administration induced a short-lived releading to macroscopic nodular masses. In mission. Pulmonary lesions and/or CNS LYG liver infiltration is not unusual. 32 % involvement are the most usual causes of of the patients presented by Liebow et a1 death. Our patient also developed massive (1972) revealed hepatic involvement at pulmonary infiltrations. Unique to this case, autopsy. However, symptoms, clinical signs however, was the severe hepatic failure and laboratory data demonstrating liver which was a probable major factor concell injury were not observed in any of tributing to the fatal outcome. their cases. REFERENCES Differential diagnoses to be considered in this case are Wegener’s granulomatosis, Hammar S & Mennemeyer R (1976) Lymphomatoid granulomatosis in a renal transplant particularly its limited form (LWG), and recipient. Hum Pathol 7, 111-16. malignant lymphoma. Classical Wegener’s Lee S C,Roth L M & Brashear R E (1976) Lymgranulomatosis (CWG) is ruled out by the phomatoid granulomatosis. A clinicopathologic absence of upper respiratory lesions and study of four cases. Cancer 38, 846-53. of focal glomerulonephritis. The daerential Liebow A A (1973) The J. Bums Amberson lecture: Pulmonary angiitis and granulomatosis. diagnosis of LWG is much more difficult, A m Rev Respir Dis 108, 1-18. since both diseases lack glomerulonephritis Liebow A A, Carrington C R & Friedmann P J and upper respiratory involvement. The two (1972) Lymphomatoid granulomatosis. Hum diseases are similar macro- and microPathol 3, 457-558. scopically, but the large number of atypical Saldana M J, Patchefsky A S, Israel H I & Atkinson G W (1977) Pulmonary argiitis and cells with proliferative activity suggests the granulomatosis. The relationship between histodiagnosis of LYG. logical features, organ involvement and reUnlike malignant lymphoma, LYG selsponse to treatment. Hum Pathol 8, 391-409. dom involves lymph nodes and spleen. Spencer H (1969) Pathology of the lung, 2nd ed, Microscopically the angiocentricity, the pp 705-32.

Lymphomatoid granulomatosis of the lung, liver and spleen.

CASE REPORT Scand J Haematol(l978) 21, 104-108 Lymphomatoid Granulomatosis of the Lung, Liver and Spleen s. A. sCHJ0LSETH & G. P.BLQM University of...
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