Pulmonary Hyalinizing Granuloma Presenting as Multiple Cavitary Calcified Nodules· Yatish lbtel, M.D.; Sadamu Ishikawa, M.D., F.C.C.P.; and Kenneth F. MacDonnell, M.D., F.C.C.P.
We describe a patient with PHG who presented with multiple cavitary calcified nodules, Laboratory evaluations revealed that she had serum immune abnormalities, and a histoplasmin skin test yielded positive results. Her Histoplasma infection may have produced a hyperimmune reaction that resulted in PHG and the calcified nodules. (Chest 1991; 100:1726-21) PHC = pulmonary hyalinizing granuloma; WBC = white blood
cell
P
ulmonary hyalinizing granuloma was first described in 1977 by Engleman et al,' who proposed that the disorder results from a hyperimmune reaction to antigens such as Histoplasma or Mycobacterium. The 20 patients discussed in their report presented with pulmonary nodules consisting of hyaline lamel1ae surrounded by lymphocytes and plasma cel1s. We describe a patient with PHG who presented with multiple cavitary calcified nodules. CASE REPORT
A 19-year-old black woman had had pleuritic chest pain on the right side, a nonproductive cou~h, fever and ni~ht sweats for /lve days, but no dyspnea or hemoptysis. On presentation, her temperature was 37.7'C, her pulse was 112 beats per minute, her respiratory rate was 20 breaths per minute and her blood pressure was 124180 mm H~. Lal~)ratory tests showed the fi>lIowing: hemoglobin, 11.5 wdl; WBC (',(llInt, 22,OOOIcu mm with 74 percent polymorphonuclear cells and 13 percent band forms; erythrocyte sedimentation rate, 100 mm/h; total protein, 8.4 wdl; albumin, 3.9 gldl; antinuclear antibody, weakly positive at 1:40; rheumatoid factor, negative; anwotensin-mnvertin~ enzyme, 29 U!L; and a1phafetoprotein and human chorionic ~onadotropin, not detected. Her alkaline phosphatase, lactic dehydro~enase, and C3 and CHSO levels were slightly elevated; the C4 level was within normal limits. A chest x-ray /lIm revealed multiple bilateral pulmonary nodules, many of which were cavitary. Computed tomography of the chest showed multiple parenchymal and subpleural cavitary nodules, 1 to 5 cm in size, in both lungs. Many of the nodules had multilobular cavities, some of which were calci/led. Figure 1 shows one of the subpleural calci/led nodules. Calci/lcation also was observed in the right hilar, posterior mediastinal and subcarinal nodes. Calci/led splenic granulomas also were present. The patient was treated with anal~esic agents, and her temperature and WBC (.'Ount became normal within four days. A Coombs' test and a tuberculin skin test yielded negative results, but a histoplasmin skin test was strongly positive (producing an induration of22x20 mm). An open-Iun~ biopsy revealed nodules in all lobes of the lungs and /lbrous exudate mvering the pleural surface. Pathologic studies of an excised nodule (4.5 x 2.0 x 2.0 cm) showed that it was /lrm and white and had a multilobulated cavity /llled with necrotic ·From the Division of Pulmonary Medicine, Department of Medicine, St. Elizabeth's Hospital; and Tufts University Sch()()1 of Medicine, Boston. Manuscript ftx.'eived June 20; revision accepted December 10. Reprint requests: Dr. Ishikawa, 736 Cambridge Street, Boston 02135
1720
FI R 1. omput d tomography 'can of h h sl howing a single subpleural cavitary nodule, which is calci/led. There is calci/lcation in the hilar and mediastinal nodes. material. MicroS(.'()py demonstrated that the nodule was mmposed of whorled broad bundles of dense lamellar /lbrosis with central areas of necrosis, without caseation (Fig 2). The periphery was rimmed by proliferating /lbroblasts and a modest lymphocytic in/lltrate. There were no giant cells. Staining of the excised tissue showed no micf()()rganisms or amyloid, and all bacterial and fungal cultures were negative. A diagnosis of PHG was made on the basis of the microsmpic /lndings. The patient received no subsequent speci/lc treatment. At a follow-up evaluation six months after presentation, her chest x-ray /lim was unchanged, her erythrocyte sedimentation rate had decreased to 32 mm/h, and her WBC count was normal. DISCUSSION
Multiple cavitary nodules in the lungs have been found to result from neoplasms, infectious granulomas, nodular sarcoidosis, rheumatoid nodules, Wegener's granulomatosis, lymphomatoid granulomatosis, plasma-cel1 granuloma, nodular amyloidosis and septic emboli.2 To our knowledge, our patient is the first observed to have PHG and multiple cavitary and calcified nodules. Patients with PHG have been found to have a number of autoimmune abnormalities, including antinuclear antibodies; rheumatoid factor; and anti-smooth-muscle, antimicrosomal and antithyroglobulin antibodies.'" Autoimmune hemolytic anemia..·• elevated levels of circulating immune complexes,3.• an increased complement level 7 and a prolonged erythrocyte sedimentation rate·· 7 may be observed.
FIGURE 2. Photomicrograph of the excised nodule showing broad bundles of hyaline lamellae irregularly arranged. The periphery is lined with proliferating /lbroblasts and lymphocytes (original magni/lcation x 100). Pulmonary Hyalinizing Granuloma (Patel. Ishikawa. MacDonnell)
Many patients with PHG also have putative immune disorders such as sclerosing mediastinitis, i.a.s retroperitoneal fibrosis'" and Riedel's thyroiditis," Staining and culture evaluations for the presence ofbacteria and fungus generally yield negative results, although a positive Histoplasma stain was reported in one case. 8 Up to 25 percent of patients with PHG have no symptoms; others have fever, malaise, weight loss, cough, dyspnea, occasional hemoptysis and chest pain. 1.3.' The disease affects mainly young and middle-aged persons-the youngest patient described was 19-and occurs at about the same rate in both sexes and all races. On roentgenographic evaluation, PHG appears as weUdefined rounded or slightly irregular nodules.P Cavitation I.? and calcification3 •5 rarely are observed. Solitary nodules, infiltrates and consolidation have been seen. 1.3 Our patient with PHG and cavitary calcified nodules had a weakly positive test for antinuclear antibodies, a slight elevation in complement levels and hyperglobulinemia. Although staining and culture assessments of an excised nodule were negative for Histoplasma, the existence of a Histoplasma infection was documented by the presence of calcified splenic granulomas and positive results on a histoplasmin skin test. The pathogenesis of PHG is unclear, but an infection with M tuberculosis, Histoplasma or other antigenic agents may trigger development of the disease.'> Yousem and Hochholzer- exclude the diagnosis of PHG if hilar or mediastinal calcification is present, but a nodule with pathologic characteristics of PHG has been found in a patient with histoplasmosis with sclerosing mediastinitis and subcarinal calcification." In our patient, therefore, an infection with Histoplasma probably triggered a hyperimmune reaction that resulted in PHG. ACKNOWLEDGMENTS: We thank Renee J. Robillard for editorial assistance and Erika L. Whitmore, M.D., for performing the pathologic studies. REFERENCES
1 Engleman P, Liebow AA, Gmelich J, Friedman PI. Pulmonary hyalinizing granuloma. Am Rev Respir Dis 1977; 115:997-1008 2 Joseph MG, Colby Tv, Swensen SJ, Mikus JP, Gaensler EA. Multiple cystic fibrohistiocystic tumors of the lung: report of two cases. MayoClin Proc 1990;65:192-97 3 Yousem SA, Hochholzer L. Pulmonary hyalinizing granuloma. AmJ Coo Patholl987; 87:1-6 4 Scholsnagle DC, Check IJ, SeweD Cvv, Plummer A, York RM, Hunter RL. Immunologic abnormalities in two patients with pulmonary hyalinizing granuloma. Am J Clin Pathol 1982; 78:231-35 5 Dent RG, Gooden OJ, Stavin PCI, Stark JE. Pulmonary hyalinising granuloma in association with retroperitoneal fibrosis.Thorax 1983; 38:955-56 6 Guccion JG, Rohatgi PK, Saini N. Pulmonary hyalinizing granuloma, electron microscopic and immunologic studies. Chest 1984; 85:571-73 7 Gans SJM, van der Elst AMC, Straks vv. Pulmonaryhyalinizing granuloma. Eur RespirJ 1988; 1:389-91 8 Chalaoui J, Gregoire P, Sylvestre J, Lefebvre R, Amyot R. Pulmonaryhyalinizing granuloma: a causeofpulmonarynodules. Radiology 1984;152:23-26 9 Ikard Rvv. Roentgenogram of the month: pulmonary hyalinizing granuloma. Chest 1988;93:871-72 10 Case records of the Massachusetts General Hospital (case 61989). N Engl J Med 1989;320:380-89
Angioimmunoblastic Lymphadenopathy Presenting as SUPerior Vena Caval Obstruction* SarUe8V Sanghvi, M.D.;t Ajeet S. Kothari, M.D.;:j: Bhushan C. Hathi, MB, BS.;§ and Raj G. Sharma, M.S.lI
A 60-year-old man presented with features of superior vena cava (SVC) obstruction. On evaluation, he was diagnosed as having angioimmullQblastic lymphadenopathy with dysproteinemia (AILD). SVC obstruction due to AILD, to our knowledge, has not been described. (Chest 1991; 100:1721-22)
=
AILD angioimmunoblastic lymp.hadenopathy with dysproteinemia; SVC= superior vena cava
.l ngioimmunoblastic lymphadenopathy with dysproteine.l'1 mia (AlLD) is an established clinicopathologic entity with a characteristic histologic picture that differentiates it from lymphoma.!" AlLD commonly presents as generalized lymphadenopathy, hepatosplenomegaly, and constitutional symptoms, ... but skin rashes and pulmonary involvement have been noted in several patients.' Occasionally, it may present with localized lymphadenopathy, Hashimoto's thyroiditis, cryoglobulinemia, and carcinoma of the pancreas.• To our knowledge, superior vena cava (SVC) obstruction as a presenting manifestation of AILD has so far not been reported. We report a patient with AILD who presented with SVC obstruction. CASE REpORT
A 60-year-old man presented with complaints of puffiness of the
face, irregular fever, headache, cough, breathlessness, and gener-
alized weaknessfor three months. There was no history of hemoptysis, orthopnea, dysphagia, urinary complaints, weight loss, skin rash, or drug ingestion. The patient used to smoke 20 cigarettes per day for the past 20 years. On examination, the face was suffused, conjunctival congestion was present, right supraclavicular, right submandibular, and bilateral axillary lymph nodes were enlarged; neck veinswere engorged, prominent veins were visible over the anterior chest wall and abdominalwallwith direction of blood flow from abovedownwards. Liver and spleen were just palpable. Results of examination of the respiratory system were normal except for a positive D'Espines sign. Other systems did not reveal any abnormality. Laboratory findings were as foDows: hemoglobin, 9 Wdl; ESR, 55 mm in first hour; total and differential leukocyte counts, peripheral blood film,and serum biochemistrywere normal;serum total protein, 6.5 g/dl, A:G ratio, 1:1.5; IgG, 1.4 Wdl; 19A, 0.35 Wdl; and IgM, 0.85 g/dl. Coombs' test was negative. Bone marrow study was normal. Sputum was negative for malignant cells and acid-fast bacilli. Skiagram of chest showed obliterilion of right costophrenic angle, with mediastinal and hilar adenopathy (Fig 1). Barium swallow study was normal. Histopathologic examination of lymph nodes showed partial effacement of lymph node architecture with proliferationof blood *From the M. G. Hospital and Dr. S. N. MedicalCollege, Jodhpur (Rajasthan) India. tAssistant Professorof Medicine. :j:Medical Officer, Medicine. §Registrar, Medicine. 'IlAssistant Professorof Surgery. CHEST I 100 I 6 I DECEMBER, 1991
1721
We describe a patient with PHG who presented with multiple cavitary calcified nodules, Laboratory evaluations revealed that she had serum immune abnormalities, and a histoplasmin skin test yielded positive results. Her Histoplasma infection may have produced a hyperimmune reaction that resulted in PHG and the calcified nodules. (Chest 1991; 100:1726-21) PHC = pulmonary hyalinizing granuloma; WBC = white blood
cell
P
ulmonary hyalinizing granuloma was first described in 1977 by Engleman et al,' who proposed that the disorder results from a hyperimmune reaction to antigens such as Histoplasma or Mycobacterium. The 20 patients discussed in their report presented with pulmonary nodules consisting of hyaline lamel1ae surrounded by lymphocytes and plasma cel1s. We describe a patient with PHG who presented with multiple cavitary calcified nodules. CASE REPORT
A 19-year-old black woman had had pleuritic chest pain on the right side, a nonproductive cou~h, fever and ni~ht sweats for /lve days, but no dyspnea or hemoptysis. On presentation, her temperature was 37.7'C, her pulse was 112 beats per minute, her respiratory rate was 20 breaths per minute and her blood pressure was 124180 mm H~. Lal~)ratory tests showed the fi>lIowing: hemoglobin, 11.5 wdl; WBC (',(llInt, 22,OOOIcu mm with 74 percent polymorphonuclear cells and 13 percent band forms; erythrocyte sedimentation rate, 100 mm/h; total protein, 8.4 wdl; albumin, 3.9 gldl; antinuclear antibody, weakly positive at 1:40; rheumatoid factor, negative; anwotensin-mnvertin~ enzyme, 29 U!L; and a1phafetoprotein and human chorionic ~onadotropin, not detected. Her alkaline phosphatase, lactic dehydro~enase, and C3 and CHSO levels were slightly elevated; the C4 level was within normal limits. A chest x-ray /lIm revealed multiple bilateral pulmonary nodules, many of which were cavitary. Computed tomography of the chest showed multiple parenchymal and subpleural cavitary nodules, 1 to 5 cm in size, in both lungs. Many of the nodules had multilobular cavities, some of which were calci/led. Figure 1 shows one of the subpleural calci/led nodules. Calci/lcation also was observed in the right hilar, posterior mediastinal and subcarinal nodes. Calci/led splenic granulomas also were present. The patient was treated with anal~esic agents, and her temperature and WBC (.'Ount became normal within four days. A Coombs' test and a tuberculin skin test yielded negative results, but a histoplasmin skin test was strongly positive (producing an induration of22x20 mm). An open-Iun~ biopsy revealed nodules in all lobes of the lungs and /lbrous exudate mvering the pleural surface. Pathologic studies of an excised nodule (4.5 x 2.0 x 2.0 cm) showed that it was /lrm and white and had a multilobulated cavity /llled with necrotic ·From the Division of Pulmonary Medicine, Department of Medicine, St. Elizabeth's Hospital; and Tufts University Sch()()1 of Medicine, Boston. Manuscript ftx.'eived June 20; revision accepted December 10. Reprint requests: Dr. Ishikawa, 736 Cambridge Street, Boston 02135
1720
FI R 1. omput d tomography 'can of h h sl howing a single subpleural cavitary nodule, which is calci/led. There is calci/lcation in the hilar and mediastinal nodes. material. MicroS(.'()py demonstrated that the nodule was mmposed of whorled broad bundles of dense lamellar /lbrosis with central areas of necrosis, without caseation (Fig 2). The periphery was rimmed by proliferating /lbroblasts and a modest lymphocytic in/lltrate. There were no giant cells. Staining of the excised tissue showed no micf()()rganisms or amyloid, and all bacterial and fungal cultures were negative. A diagnosis of PHG was made on the basis of the microsmpic /lndings. The patient received no subsequent speci/lc treatment. At a follow-up evaluation six months after presentation, her chest x-ray /lim was unchanged, her erythrocyte sedimentation rate had decreased to 32 mm/h, and her WBC count was normal. DISCUSSION
Multiple cavitary nodules in the lungs have been found to result from neoplasms, infectious granulomas, nodular sarcoidosis, rheumatoid nodules, Wegener's granulomatosis, lymphomatoid granulomatosis, plasma-cel1 granuloma, nodular amyloidosis and septic emboli.2 To our knowledge, our patient is the first observed to have PHG and multiple cavitary and calcified nodules. Patients with PHG have been found to have a number of autoimmune abnormalities, including antinuclear antibodies; rheumatoid factor; and anti-smooth-muscle, antimicrosomal and antithyroglobulin antibodies.'" Autoimmune hemolytic anemia..·• elevated levels of circulating immune complexes,3.• an increased complement level 7 and a prolonged erythrocyte sedimentation rate·· 7 may be observed.
FIGURE 2. Photomicrograph of the excised nodule showing broad bundles of hyaline lamellae irregularly arranged. The periphery is lined with proliferating /lbroblasts and lymphocytes (original magni/lcation x 100). Pulmonary Hyalinizing Granuloma (Patel. Ishikawa. MacDonnell)
Many patients with PHG also have putative immune disorders such as sclerosing mediastinitis, i.a.s retroperitoneal fibrosis'" and Riedel's thyroiditis," Staining and culture evaluations for the presence ofbacteria and fungus generally yield negative results, although a positive Histoplasma stain was reported in one case. 8 Up to 25 percent of patients with PHG have no symptoms; others have fever, malaise, weight loss, cough, dyspnea, occasional hemoptysis and chest pain. 1.3.' The disease affects mainly young and middle-aged persons-the youngest patient described was 19-and occurs at about the same rate in both sexes and all races. On roentgenographic evaluation, PHG appears as weUdefined rounded or slightly irregular nodules.P Cavitation I.? and calcification3 •5 rarely are observed. Solitary nodules, infiltrates and consolidation have been seen. 1.3 Our patient with PHG and cavitary calcified nodules had a weakly positive test for antinuclear antibodies, a slight elevation in complement levels and hyperglobulinemia. Although staining and culture assessments of an excised nodule were negative for Histoplasma, the existence of a Histoplasma infection was documented by the presence of calcified splenic granulomas and positive results on a histoplasmin skin test. The pathogenesis of PHG is unclear, but an infection with M tuberculosis, Histoplasma or other antigenic agents may trigger development of the disease.'> Yousem and Hochholzer- exclude the diagnosis of PHG if hilar or mediastinal calcification is present, but a nodule with pathologic characteristics of PHG has been found in a patient with histoplasmosis with sclerosing mediastinitis and subcarinal calcification." In our patient, therefore, an infection with Histoplasma probably triggered a hyperimmune reaction that resulted in PHG. ACKNOWLEDGMENTS: We thank Renee J. Robillard for editorial assistance and Erika L. Whitmore, M.D., for performing the pathologic studies. REFERENCES
1 Engleman P, Liebow AA, Gmelich J, Friedman PI. Pulmonary hyalinizing granuloma. Am Rev Respir Dis 1977; 115:997-1008 2 Joseph MG, Colby Tv, Swensen SJ, Mikus JP, Gaensler EA. Multiple cystic fibrohistiocystic tumors of the lung: report of two cases. MayoClin Proc 1990;65:192-97 3 Yousem SA, Hochholzer L. Pulmonary hyalinizing granuloma. AmJ Coo Patholl987; 87:1-6 4 Scholsnagle DC, Check IJ, SeweD Cvv, Plummer A, York RM, Hunter RL. Immunologic abnormalities in two patients with pulmonary hyalinizing granuloma. Am J Clin Pathol 1982; 78:231-35 5 Dent RG, Gooden OJ, Stavin PCI, Stark JE. Pulmonary hyalinising granuloma in association with retroperitoneal fibrosis.Thorax 1983; 38:955-56 6 Guccion JG, Rohatgi PK, Saini N. Pulmonary hyalinizing granuloma, electron microscopic and immunologic studies. Chest 1984; 85:571-73 7 Gans SJM, van der Elst AMC, Straks vv. Pulmonaryhyalinizing granuloma. Eur RespirJ 1988; 1:389-91 8 Chalaoui J, Gregoire P, Sylvestre J, Lefebvre R, Amyot R. Pulmonaryhyalinizing granuloma: a causeofpulmonarynodules. Radiology 1984;152:23-26 9 Ikard Rvv. Roentgenogram of the month: pulmonary hyalinizing granuloma. Chest 1988;93:871-72 10 Case records of the Massachusetts General Hospital (case 61989). N Engl J Med 1989;320:380-89
Angioimmunoblastic Lymphadenopathy Presenting as SUPerior Vena Caval Obstruction* SarUe8V Sanghvi, M.D.;t Ajeet S. Kothari, M.D.;:j: Bhushan C. Hathi, MB, BS.;§ and Raj G. Sharma, M.S.lI
A 60-year-old man presented with features of superior vena cava (SVC) obstruction. On evaluation, he was diagnosed as having angioimmullQblastic lymphadenopathy with dysproteinemia (AILD). SVC obstruction due to AILD, to our knowledge, has not been described. (Chest 1991; 100:1721-22)
=
AILD angioimmunoblastic lymp.hadenopathy with dysproteinemia; SVC= superior vena cava
.l ngioimmunoblastic lymphadenopathy with dysproteine.l'1 mia (AlLD) is an established clinicopathologic entity with a characteristic histologic picture that differentiates it from lymphoma.!" AlLD commonly presents as generalized lymphadenopathy, hepatosplenomegaly, and constitutional symptoms, ... but skin rashes and pulmonary involvement have been noted in several patients.' Occasionally, it may present with localized lymphadenopathy, Hashimoto's thyroiditis, cryoglobulinemia, and carcinoma of the pancreas.• To our knowledge, superior vena cava (SVC) obstruction as a presenting manifestation of AILD has so far not been reported. We report a patient with AILD who presented with SVC obstruction. CASE REpORT
A 60-year-old man presented with complaints of puffiness of the
face, irregular fever, headache, cough, breathlessness, and gener-
alized weaknessfor three months. There was no history of hemoptysis, orthopnea, dysphagia, urinary complaints, weight loss, skin rash, or drug ingestion. The patient used to smoke 20 cigarettes per day for the past 20 years. On examination, the face was suffused, conjunctival congestion was present, right supraclavicular, right submandibular, and bilateral axillary lymph nodes were enlarged; neck veinswere engorged, prominent veins were visible over the anterior chest wall and abdominalwallwith direction of blood flow from abovedownwards. Liver and spleen were just palpable. Results of examination of the respiratory system were normal except for a positive D'Espines sign. Other systems did not reveal any abnormality. Laboratory findings were as foDows: hemoglobin, 9 Wdl; ESR, 55 mm in first hour; total and differential leukocyte counts, peripheral blood film,and serum biochemistrywere normal;serum total protein, 6.5 g/dl, A:G ratio, 1:1.5; IgG, 1.4 Wdl; 19A, 0.35 Wdl; and IgM, 0.85 g/dl. Coombs' test was negative. Bone marrow study was normal. Sputum was negative for malignant cells and acid-fast bacilli. Skiagram of chest showed obliterilion of right costophrenic angle, with mediastinal and hilar adenopathy (Fig 1). Barium swallow study was normal. Histopathologic examination of lymph nodes showed partial effacement of lymph node architecture with proliferationof blood *From the M. G. Hospital and Dr. S. N. MedicalCollege, Jodhpur (Rajasthan) India. tAssistant Professorof Medicine. :j:Medical Officer, Medicine. §Registrar, Medicine. 'IlAssistant Professorof Surgery. CHEST I 100 I 6 I DECEMBER, 1991
1721
