Unusual Initial Calcification of Primary and Metastatic Seminomas

Finally, carotid sinus hypersensitivity has been found in up to 30 percent of elderly patients with hypertension and <:oronary artery disease . " Thus, it may be that the coexistence of both reflexes is a mere l'Oincidence . Further studies are needed to solve this problem .

REFEHENCES Lichstein E . Chadda KIJ . Atrioventricular block produced by with documentation by His bundle re<."rdiu~. Am J Cardiol 1972; 29:561-63 Kadish AH, We<:hsler L. Mar<:hlinski FE . Swallowin~ syncope: obst>rvatious in tht> absence of l"nduction systt>m or t>sophageal dist>ase. Am J Med 1986: I:H :1W8-1UO Naka~awa S, Hisana~a S, Kondoh H, Koiwaya Y, Tanaka K. A cast> of swallow synl"pe induced by va~otonic vis<:eral reflex rt>sulting in atrioventricular node suppression. Electrocardiology 1Yil7: 20:65-9 Weiss S, Ferris EB Jr. Adams-Stokes syndrome with transient <."mplete heart blo<:k of vagova~al reflex ori~in : mechauism and treatment. Arch Intern Med 1934; 54 :931-51 Armstrong P\V, McMillan DG, Simon JB. Swallow syn<..,pe . Can Med Asso<: J 1Yil5; 132:1281-114 1glau"r S, Schwartz BA . Heart block periodi<:ally indut:ed by the swallowing of lOud in a patient with cardiospasm (vagovagal synwpe). Ann Otol 1936; 45:875-llO Correll HL , Lindert MCF. Vagovagal synwpe: report of a case apparently induced by digitalization. Am Heart J 1949; 37:44654 James AH , Oxon OM. Cardiac synl"pe after swallowing. Lancet 1958; 1:771-72 Kopald HH, Roth HP, Fleshier B. Pritchard WH. Vagovagal synl'>pe: report of a case associated with diffuse esophageal spasm . N Engl J Med 1964; 271 :1238-41 '1(,1man KG , Ashworth WD . Syncope induced by dysphagia: corrt>dion by esophageal dilatation . Am J Dig Dis 1971; 16:102631 Alstrup P, Pedersen SA . A case of syncope on swallowing St'<."ndary to diffuse oesophageal spasm. Acta Med Scand 1973; 193:365-68 Brick JE, Lowther CM , Deglin SM . Cold water synmpe. South Med J 1978; 71 :1579-llO Bortolotti M, Ciringotta F. Labs G. Atrioventrintlar block induced by swallowing in a patient with diffuse esophageal spasm. JAMA 1982; 248:2297-99 Strasberg B,Lam \V, Swiryn S, Bavernfiend R, Scagliotti D . Palileo E, et al. Symptomatic spontaneous paroxysmal A-V nodal block due to localized hyperresponsiveness of the A-V node to vagotonic reflexes. Am Heart J 1Yil2; 103:795-ll01 Strasberg B, Sagie A, Erdman S, Kusniec J, Sdarovsky S. Agmon J. Carotid sinus hypersensitivity and carotid sinus syndrome . Prug Cardiovast· Dis 1Yil9; 31 :379-91

Rare large ab initio calcifications of a primary mediastinal seminoma in a 16-year-old boy and of para-aortic nodal metastatic ovarian seminoma in a 14-year-old girl are demonstrated with but not with conventional radiography. They are most likely dystrophic calcifications because of the absence of other germ cell tumor components and infective granulomatous disease. Routine use of CT might detect more such calcifications in untreated seminoma.

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(Chest 1991; 99:1543-45)

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T

esticular seminoma, ovarian dysgerminoma aml extragonadal germinoma are the same malignant neoplasms of identical histology. '-" We prefer the term seminoma li1r all of them regardless of the location or origin. Although li1ci of ischemic necrosis are very common in seminoma , dystrophic calcification and cyst formation are extremely rare, particularly before chemotherapy or radiotherapy. ' Demonstrated here are two unusual cases of seminomas with ab initiu calcifications which were not detected by l'Onventional radiography but dearly shown on CT. Tht> possible medlanisms for such calcifications are briefly discussed . CASE REPOHTS A 16-year-old boy was admitted bet:ause of in<:reasin~ l"u~h productive of white sputum and o<:casional streaks of blood, chills and fever and mild shortness of breath f(,,. two weeks. Chest radio~raphy revealed a large right upper mediastinal mass with no obvious calcification and right pleural eftitsion. Thorad<: CT showed an irregular inhomogeneous mediastinal mass extending from the anterior chest wall to tht> paravertebral lo<:ation with areas of low attenuation (Fig 1). A lil.irly large ring-like l'alcifi<:ation (2.0 x 1..'5 em) and several stippled caldfications also wert> noted in the centt>r of the mass. Biopsy of the enlarged <:t>rvi<:al lymph nodes showed a classic histologic feature of seminoma with lymphocytic infiltration and granulomatous reaction to the tumor l'ells. Extensive sear<:h of the biopsied specimen failed to identil)· syncytiotrophohlasts or other nonseminomatous <.:omponents of germ l'ell tumor. Serum alpha-fetoprotein and beta-human chorionic gonadotropin were all negative. The serum calcium level was within normal limits. The size of the tumor decreased drastically after tht> first course of chemotherapy <.vmposed of cis-platinum, vinblastine and hleomydn

Unusual Initial Calcification of Primary and Metastatic Seminomas* Detection by Computed Tomography Myuug S. Shirt, M.D ., J.:C.C: .P.; Gregory 'f Odrc;:in, M.D.; jerald A. Van Dyke, M.D.; aud &mg-Jey Ho , M .D., Ph.D. *From the Department of Radiology (Drs. Shin, Odrezin and Van Dyke) and PatholoJ.,'Y (Dr. Ho), School of Medicine, University of Alabama at Birmingham, and Veterans Administration Medical Ce nter, Birmingham , AL. Reptiut requt•sls: Dr: Shiu, Deparltlwnl uf Radiology, University of Alabama Hospital. 619 South 19th Street, Binningham 35233

FtGUIIE 1. Chest C..'T in case 1 showin~ a large mediastinal mass with a ring-like <:alcifi<:ation (2 .0 x 1.5 <:m) and se\·eral stippled calcifications before treatment. CHEST I 99 I 6 I JUNE. 1991

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Fat:trau: 2. Abdominal CT in case 2 showing several irregular large calcifications in the t•nlarged mattt•d para-aortic lymph nodes. and decreased liartht·r after subsequent <.'mrses, with no chauge in the shape aud size of the calcifications. CASE

2

A 14-year-old girl <."mplained of intermittent sharp left lower ahdorniual paiu with easy fatigability. weight loss. low-grade ft•wr fc>r 3 to 4 months aud gradual alxlominal enlargement fc>r two weeks. A very firm aud irregular mass, measuring approximat .. ly 7 X 10 e m, was palpable in the left lower quadrant of the alxlomt•u t'XIt'ndiug lrona tilt' pdvis to the umbilicus. Alxlominal and dlt'st CT showed bulky lymphadenopathy throughout the chest, alxlomt•n and pelvis and ahst'uce of a mass lt•sion in the lungs, livt•r and spleen. Areas of low attenuation were noted in the pelvic mass and enlarged lymph nodes. In addition, several irrt'gular, large calcifications were noted in the para-aortic mass lesions (I'ig 2). Such caleifications Wt're not set'u iu tht' plain abdominal x-ray film. llyper<.·alcemia (15 mg.'dl) was present. Biopsy of the pelvic mass revealed a seminoma with both lymphocytic infiltrate and gnmulomatous reaction to the tumor cells. The tumor eells were rich in gly<.,.gen and, by immunohistoehemical technir placental alkaline phosphatase hut negatiw fc>r cytokeratin. No other <.'>mponents of germ cell tumor were identified in the hiopsied tissue and the serum alpha-lt·toprotein and heta-lmman chorionic gonadotropin were negative. Her hypercalcemia was helit•\·ed to he most likely se<.'>ndary to ectopic parathyroid hormtmt' secretion by the tumor lxx·aust· of disproportional elevation of serum parathyroid hormone leVt·l mpared with the calcium level; the caleium lt·vel decreased somewhat when therapy with diuretics and caldtonin was used, hut not significantly until chemothe rapy was iustitutcd . DISCLISSJO:'II

Seminoma of the testis, ovary and extragonadal location is a germ cell tumor with a spermatogonium line of diflerentiation.' In the pediatric age group, the most common sites f(,r seminoma are tlw ovary (case 2). anterior mediastinum (case 1), pineal area and undescended testis, but not the normal h'stis.' 1 This tumor of relatively low malignancy tt•nds to metastasize to the regional lymph nodes particularly along the large vessels such as the para-aortic lymph nodes (case 2), mU<:h less commonly to parenchymatous organs such as the lungs and liver.' ·' Seminomas are extrt'mely radiosensitive and also respond well to chemotherapy." For advanced seminoma as in the present two patients, chemotherapy is the treatment of choice becaust• radiotht•rapy has 1544

a relapse rate of up to 40 percent. ' Computed tomography now is routinely used in evaluation of the extt•nt of seminoma and in followup of its responsiveness to therapy; CT of the seminoma is characterized by tlw presence of irregular, small and large , low attenuation areas within the tumor mass (Fig 1 and 2).' In review of the chest radiographs and CT scans of2(X) patit•nts with pure tt-sticular seminoma, Williams et al' detected no calcification in any metastatic lesions. No calcification could be observed by Stomper t't al" in nodal metastases of advanced primary pure tt>sticular St'minomas in 1H patients helilrt' therapy. Prechemotherapy calcification of para-aortic nodal metastases of a pure testicular seminoma similar to case 2 has, however. been reported in one patie nt.' Pretreatment calcification of the primary mediastinal seminoma such as in case I has not Iwen previously described . Ab i11itiu calcification of seminoma might not he as rare as we havt• believed . Routine use ofCT might detect more such calcification since CT is mort• sensitive than conventional radiography in this aspect. Thert• arc at lt•ast three possibilities for the presence of calcifications in seminoma in our two patients. One possibility is the presence of other histologic types of germ cell tumors. About two thirds of tt•sticular germ cell neoplasms consist of more than one histologic type .' Among various germ cell tumors, teratoma and teratocarcinoma may contain calcified structures." It is possible that the seminomas in thest• two patients might havt• teratomatous areas. However, the li1llowing facts argue against such a notion. The serum alpha-letopmtein and beta-human chorionic gonadotropin in these two subjects were not elevated . Calcification in teratoma usually is stippled, rarely reaching such a large size as seen in our patients." Thorough examination of the biopsied tissue specimens failed to detect teratoma or other t~lmpotlt'nts of a germ cell tumor. Calcified infective granuloma unrelated to seminoma is another possibility. It is also unlikely because isolated calcified granulomas in the para-aortic lymph nodes (case 2) are extremely uncommon. The calcification in the mediastinal mass in case 1 is too large for usual infective granuloma and is not accompanied hy calcified or noncalcified disease lix:i in the lung parenchyma. The third and most attractive possibility is dystrophic calcification. Postchemotherapy dystrophic calcification of metastatic seminomas has been re1>or!t'd in two of 1H patients." The low attenuation areas commonly seen in seminomas correspond to the f(,ci of ischemic necrosis. Such necrotic areas are susceptible to dystrophic calcification, particularly in the prest•nce of hypercalcemia which was present in case 2.

Gordon A. Liptou D . \VotKinafl' JD. Dysgerminoma. a review of 15/i cases from the Emil Novak ovarian tumor registry. Ohstet Gyut'<.'~l 1Yil1 ; .'5/l:497-504 2 Rubinstein LJ. Cytoge nesis and differentiation of pineal neoplasms. llumau Pathol IY/l1; 12:441-48 .1 Mostofi FK, Sesterhe nn lA . Pathology of germ cdl tumors of testes. Prog Clin Bioi Res I WS-'5; 203:1-34 4 Williams MP. Husband JE, llt•ron C\V. Intrathoracic manifestatimas of mdastatic testicular seminoma: a <.'>mparison of chest radiographil· and cr findings. AJR IY/l7; 149:47:3-75 Calcification of Primary and Metastatic Seminomas (Shin eta/)

5 Yousem DM , Scatarige JC, Fishman EK, Siegelman SS. Lowattenuation thoracic metastases in testicular malignancy. AJR 1986; 146:291-93 6 Stomper PC, Jochelson MS, Friedman EL, Garnick MB, Richie JP. Cf evaluation of advanced seminoma treated with chemotherapy. AJR 1986; 146:745-48 7 Maier JG , Sulak MH. Radiation therapy in malignant testis tumors. 1: seminoma. Cancer 1973; 32:1212-16 8 Thornton A, Pancharatnam MD. Testicular tumor presenting with lymph node calcification on computed tomography: a case report. Cf: J Comput Tomogr 1984; 8:245-48 9 LeeKS, ImJG, HanCH , Han MC, KimCW, KimWS . Malignant primary germ cell tumors of the mediastinum: Cf features. AJR 1989; 153:947-51

Intermediate Alpha1-Antitrypsin Deficiency with Apical Lung Bullae and Spontaneous Pneumothorax* Presence of a Z Variant In an American Black Said Mostafavi, M .D., and jack Lieberman, M.D. , F.C.C .P.

A 43-year-old black man had an 18-year history of apical lung cystic-bullous disease. Following two episodes of spontaneous pneumothorax and two instances of thoracotomy for bullectomy and pleural abrasion, he was found to have an intermediate AAT deficiency with an MZ phe. . type. It is believed that this is the first case of localized bullous lung disease to be reported in association with any degree of AAT deficiency. There is evidence that the cystic lesions progressed to form upper lobe bullae. It is postulated that the AAT deficiency may have played a role in this progression, as did the patient's cigarette smoking. Following two instances of surgery, cr scans of the lungs, compliance studies and complete pulmonary function tests show no further evidence of lung bullae or emphysema. The rarity of the Z variant of AAT in blacks is discussed. (Chen 1991; 99:1545-46) AAT = alpha,-antitrypsin; Dsb =single-breath carbon monoxide diffusing capacity; TLC =total lung capacity

CASE HISTORY

A 43-year-old black American man was first seen in 1974 with dyspnea on exertion of two years' duration. He had smoked 1 to 1'12 packs of cigarettes per day for ten years. Chest x-ray films in 1974 showed severe bullous emphysema of the right upper lobe and two emphysematous blebs of the left apex. Unfortunately, these x-ray films are not available for reproduction at this time. A perfusion scan showed absence of perfusion of the right upper lobe with decreased perfusion of the apical portion of the left upper lobe. A ventilation scan showed decreased ventilation of both upper lobes, with the right being worse than the left; the washout phase showed retention of tracer in the upper lung fields bilaterally. A Dsb was slightly reduced (65 percent of predicted) but normal when corrected for the diffusion lung volume. Lung spirometry showed only mild restrictive and obstructive changes and normal arterial blood gas levels. The TLC was 5.68 L when measured by plethysmography, but measured 4.88 L by the dilution of helium from the 10-s diffusion capacity measurement; this dilference in TLC by the two measurements suggested that the volume of bullae was approximately 0.8 L. A serum protein electrophoresis showed the presence of an alpha,-globulin peak measuring 0.1 mg percent which was at the lower limits of normal. In December of 1974, the patient suffered a spontaneous pneumothorax of the right side of the chest, which responded to therapy with a chest tube. In February of 1975, he was readmitted for elective surgery to include a bullectomy and pleural stripping of the right lung. An angiogram prior to surgery showed normal vasculature to the lower lung fields with absent vasculature in the area of the bullae, and with some compression of the right and left lower lung fields. At surgery, large bullae were found in the right upper lobe along with a few smaller blebs in the right upper lobe as well as in the right middle and lower lobes. In February of 1989, the patient awoke with pleuritic left chest pain and dyspnea. Achest x-ray film now showed a 70 to 80 percent pneumothorax on the left side. This was treated at another hospital with chest tube reexpansion. After reinflation, a chest x-ray film then showed a large left apical bulla (Fig 1). At exploratory thoracotomy, multiple blebs and bullae were found in the left upper lobe; these were excised and a pleural abrasion was performed with sterile gauze. During a follow-up examination in September 1989 at the Sepulveda VA Medical Center Chest Clinic, the patient was tested for his antitrypsin status. He was found to have an intermediate deficiency (AAT concentration, 125 mg percent; severe deficiency, less than 80 mg percent; intermediate deficiency, 80 to 170 mg percent) by radial immunodiffusion (Kallestad Diagnostics; Endo-

,llpha,-antitrypsin deficiency is well recognized as a pre-".: disposing factor toward the development of obstructive lung disease, usually panacinar emphysema.' The Z variant of AAT, which is the most common cause of the deficiency, is quite rare in blacks and has not been reported previously in association with localized bullous lung disease or with spontaneous pneumothorax in any race. The present report involves a black male patient with an MZ phenotype for AAT associated with localized, bilateral, bullous disease and episodes of spontaneous pneumothorax. *From the Respiratory Disease Division, Veterans Administration Medical Center, Sepulveda, CA, and the UCLA School of Medicine, Los Angeles. Su_pported in part by the Medical Research Service of the Veterans Administration and the Neil Simon Charitable Directed Fund. Reprint requests: Dr. Lieberman VA Medical Center; 16111 Plummer; Sepulveda, California 91343

FIGURE 1. Expiratory chest x-ray showing large left upper lobe bulla with some depression of the left hilar vasculature. Staples from previous right-sided bullectomy are visible. CHEST I 99 I 6 I JUNE, 1991

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