Some unusual lesions of the mediastinum: Roentgenologic and pathologic features

Some Unusual Roentgenologic

Lesions of the Mediastinum: and Pathologic Features

By LISELOTTE HOCHHOLZER, M.D., COMMANDER ELIAS G. THEROS, MC, USN AND SAMUEL H. ROSEN, M.D. N HIS EVALUATION OF MEDIASTINAL LESIONS, the radiologist finds it strategic to guide on the statistics of location. He has learned, for example, that thymic and teratoid tumors are almost invariably located in the anterior mediastinum and that neurogenic tumors find their home in the posterior mediastinum. He also is well aware that most masses in the middle media&mum are the result of adenopathy, inflammatory or neoplastic. He has learned, too, that when location is considered with other reliable indicators such as size, contour, density, and the like, he is often able to arrive at a specific diagnosis. Occasionally, however, these guidelines fail because of the presence of an unusual pathologic entity whose ultimate labeling can be accomplished only through tissue analysis by the pathologist. It is the purpose of this paper to call attention to some of these unusual conditions and to describe their gross and microscopic, as well as their radiologic, features, thus enlarging the gamut of possibilities the radiologist must consider in his probing of the mediastinum. The disease entities chosen are approached as diagnostic problems, with a brief case presentation and a discussion of each subject, supported by typical illustrations and a selected bibliography. CASE 1 Radiologic Findings. The chest roentgenograms of an asymptomatic 51 year old woman reveal a rounded mass of homogeneous density located low in the posterior mediastinum in a right paravertebral location (Fig. 1). These findings, along with the smooth contour, suggest a neurilemoma or neurofibroma, lesions of frequent occurrence in this area. The absence of erosion of the intervertebral foramina (Fig. 1B) does not rule out neurogenic tumor. The overall appearance is certainly also compatible with a cyst. Gastroenteric and even bronchogenic cyst must be considered although they tend to occur closer to the middle mediastinal area, particularly in the juxtacarinal zone. One may add the rare lateral meningocele to the gamut of possibilities, but then widening of an intervertebral space would be even more crucial for corroborating evidence. Another rare entity peculiar to this location is a focus of extramedullary hematopoiesis, although these are seldom as large as the lesion in Figure 1 and are most frequently multiple. From the Chest Tumor Registry and the Registry of Radiologic Pathology, Armed Forces Institute of Pathology, and the Veterans Administration Special Reference Laboratory for Pathology at the AFIP, Washington, D. C. LISELOTTE HOCHHOLZER, M.D.: Associate Pathologist, Pulmonury and Mediastinal Pathology Branch, AFIP. COMMANDER ELIAS C. THEROS, MC, USN: Chief, Radiologic Pathology Branch; Registrar of Registry of Radiologic Pathology, AFIP. SAMUEL H. ROSEN,M.D.: Chief, Pulmonary and Mediastinal Pathology Branch; Registrar of Chest Tumor Registry, AFIP. 74

SEMINARS IN ROENTGENOLOGY, VOL. 4, No.

1 (JANUARY ), 1969

UNUSUAL LESIONS

75

Fig. I.-(AFIP Negatives 64-12238-1 and 2). Case 1. Posterior mediastinal mass in an asymptomatic 51 year old woman. The location and apparent smooth margin of the lesion suggest a neurogenic tumor. Gastroenteric or bronchogenic cyst must also be considered. Clinical Data. On physical examination the only abnormality noted was an enlarged spleen three fingerbreadths below the left costal margin. The laboratory work-up was reported as negative. Past history was noncontributory, except that the patient’s son had had a splenectomy for congenital hemolytic anemia. Pathologic Findilzgs. Figure 2 shows pieces of the encapsulated, soft, ovoid tumor found in the right posterior mediastinum adherent to the periosteum of the vertebral bodies, The tumor measured 8.5 cm. in greatest dimension. It was dark red and friable resembling clotted blood. Microscopically, under low magnification one sees an admixture of blood cells and fat cells closely resembling bone marrow (Fig. 3h). High magni&zation reveals that the hematopoietic elements consist of megakaryocytes, normoblasts, white cell precursors, numerous erythrocytes, and relatively few mature leukocytes ( Fig. 3B). ,I..

Fig. 2.-(AFIP Negative 64-12137). Case 1. Gross appearance of tumor. Pieces of the posterior mediastinal tumor. The outer surface (left) is ‘covered by a thin‘ capsule. The cut surface (right) is dark red and the friability of the tissue is indicated by its irregular separation from the capsule. It resembled clotted blood.

76

HOCHHOLZER,

THEROS

AND

ROSEN

Fig. 3.-(AFII? Negative 66-3779). Case 1. Histologic appearance. A. Low power photomicrograph shows an admixture of blood and fat cells resembling bone marrow. B. (AFIP Negative 66-3711). In this higher power photomicrograph one can distinguish megakaryocytes, normoblasts, and erythrocytes.

Pathologic Diagnosis. Tumor-like

extramedullary

hematopoiesis

of the pos-

terior mediastinum. DISCUSSION

Tumor-like extramedullary hematopoiesis1-5 is certainly an unusual condition. Ordinary extramedullary hematopoiesis involves potential blood-forming organs such as liver, spleen, and lymph nodes in a diffuse manner. It is a compensatory phenomenon in a variety of diseases in which there is either inadequate production or excessive destruction of blood cells. Rarely, however, the extramedullary hematopoiesis manifests itself in the form of a tumor-like mass. These are often multiple and bilateral and show a predilection for the thoracic paravertebral area, Usually they are asymptomatic and are detected on routine radiographs or as an incidental autopsy finding. h ere are about 25 cases of tumor-like extramedullary hematopoiesis recorded in the literature and only 3 cases in the AFIP files. Most were associated with hereditary or congenital hemolytic anemia and, therefore, might be considered a manifestation of secondary or compensatory hematopoiesis. A few had no apparent blood dyscrasia and may represent primary or idiopathic extramedullary hematopoiesis. How and why the latter originate is obscure. In the present instance, the familial history of hemolytic anemia and the enlarged spleen suggest that the condition was secondary. The average age of the patients in the literature was 55 years, suggesting that in most instances it may take many years for the hematopoietic stimulus to produce a mass large enough to become detectable on radiographs. This entity has also been called ectopic or heterotopic bone marrow and myelolipoma. It is well for the radiologist to keep this lesion in mind when he encounters posterior mediastinal masses in patients with hemolytic anemia or with a familial history of this condition.

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77

LESIONS CASE 2

Radiologic Findings. The chest films of a 28 year old man show a large mass extending from the anterior mediastinum into the right thorax (Fig. 4). The edge is irregular and lobulated, an appearance that may augur a thymic or teratoid lesion or even lymphoma, although the unilaterality of the mass speaks against the latter. The lack of a “sulcus sign” (intervening air lucency where the edges of the mass meet the posterior surface of the sternum on the lateral view) favors a teratoid over a thymic lesion, as does the large size of the mass. The sulcus sign is not infallible, however, particularly when the lesions are large. ClinicaE Data. This asymptomatic patient had been admitted to the hospital for mental confusion, Physical examination and laboratory studies were normal. A right thoracotomy confirmed the presence of the mass in the anterior mediastinum. It was 10 to 12 cm. in greatest diameter and its base measured 6 to 8 cm. and overlay the right atrium. It had a pedicle which measured about 2 x 8 cm. and was attached to the mediastinum just below. the right hilum. A separate nodule, 4 cm. in diameter, was found in the region of the thymus. The entire mass was resected, along with the separate nodule and adherent portion of the pericardium. The patient tolerated the operation well. During the immediate postoperative period he developed a “myasthenia-like crisis” characterized by severe respiratory diaculty, which lasted about 5 hours. He was discharged on the 15th hospital day, asymptomatic. Pathologic Findings. The resected mass weighed 612 Gm. and measured 17 x 12 x 8.5 cm. It was encapsulated, lobulated, firm, and resilient, and was covered by fibrofatty tissue. The separate nodule was found along the attachment of the mass. The cut surfaces of the mass and nodule (Fig. 5) were tan

Fig. 4.-(AFIP

Negatives

63-6297-2

and 4). Case 2. Anterior

mediastinal

mass.

The chest films of this asymptomatic 28 year old man show a large mass extending into the right thorax from the anterior mediastinum. A. The edge of the mass is irregular and polycyclic. The appearance and Iocation strongly suggest a thymic or teratoid lesion, particularly in view of the unilaterality and size of the mass, B. Note that its apposition against the sternum is irregular and ill-defined, a finding favoring a teratoid over a thymic lesion.

HOCHHOLZER,

THEROS

AND

ROSEN

Fig. 5.-(AFIP Negative 64-2937-2). Case 2. Cut surfaces of the anterior mediastinal tumor and adjacent small nodule. The tumor is divided by fibrous septa into bulging, irregular

pseudolobules which project outward at the periphery and explain the irregular polycyclic appearance on the roentgenogram.

to gray and irregularly divided into bulging pseudolobules of variable size by fibrous bands extending from the periphery to the center. Figure 6 reveals the tumor composition of uniform large, round, or polyhedral cells containing centrally placed, deeply chromatic round nuclei with one or two fairly prominent nucleoli. Their cytoplasm varies from pale to more deeply staining, and the cell borders are fairly distinct in the areas that are better preserved. The cells are arranged in variable-sized nests and cords separated by fine strands of connective tissue infiltrated by lymphocytes (lymphoid stroma). In other areas the stroma was granulomatous with epithelioid cells and an occasional Langhans giant cell. The granulomatous stroma may become transformed into fibrous stroma. The separate nodule described grossly showed identical histologic features. In the fibrofatty tissues surrounding the thick fibrous capsule of the large mass were remnants of involuted thymic tissue.

Fig. 6.-(AFIP Negative 63-50). ( Medium power photomicrograph wing histologic pattern: nests of form, moderately large cells with dark nuclei, separated by thin connective tis-

2.

sue septa infiltrated lohoid stroma).I (lvn .z I

by lymphocytes

Other secl showed a prominent granulomatous stroma with epithelioid cells and an occasi onal Langhans giant cell.

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79

LESIONS

Pathologic astinum.

Diugn.osis. Primary seminoma ( gemnnoma)

of the anterior medi-

DISCUSSION

Primary seminoma (germinoma) of the mediastinum+” is a rare neoplasm that is invariably located in the anterior mediastinum in relation to the thymus gland. Among other names that have been applied to it are seminomutous thymoma and seminoma-like tumor of the thymus. Its cell structure and histologic pattern, however, are identical to those of testicular seminoma and ovarian dysgerminoma, although the granulomatous stroma appears to be a more conspicuous feature of the mediastinal tumor. Since, therefore, it is indistinguishable in histologic features as well as in biologic behavior from its adult and gonadal counterparts, and since other teratoid tumors-namely, malignant teratoma, embryonal carcinoma, choriocarcinoma-are also recognized as arising in the mediastinum, we find no reason for not calling it seminomu or germinoma of the mediastinum. Mediastinal seminoma occurs almost exclusively in men, predominantly in young men, with an average age of 27 years in the AFIP series. Presently, there are at least 41 cases of pure mediastinal seminoma in the AFIP files and at least 25 in the literature. Many theories have been propounded concerning the origin of this tumor; an attractive one suggests that it arises from aberrant germ cells that have wandered into the foregut during embryogenesis and thence into the thymus or anterior mediastinum. Usually remnants of thymic tissue can be found within the tumor, in its capsule, or in the adjacent fibrofatty tissue, as is the case with other teratoid tumors of the mediastinum. The tumor may be completely encapsulated; or it may be locally invasive, fixed to the adjacent mediastinal structures, and inoperable. Like its gonadal counterparts (the testicular seminoma and ovarian dysgerminoma), however, it is very radiosensitive and can be controlled and apparently even cured by radiotherapy with or without surgical treatment. The prognosis, therefore, is relatively good, especially for the well-encapsulated tumors. However, distant metastasis may sometimes occur many years later. The patient may be completely asymptomatic and the tumor discovered on a routine chest film. Signs and symptoms, when present, are the same as those of other invasive lesions of the mediastinum: chest pain, substemal pressure, dyspnea, cough, weight loss, weakness, and symptoms of superior vena caval obstruction. The following features make this case unusual: (1) it is one of the largest, if not the largest, among the mediastinal seminomas reported; (2) the development of severe respiratory distress followed its removal. CASE

3

Radiologic Findings. The pre-employment chest examination of an asymptomatic 18 year old youth resulted in his referral for evaluation of cardiac enlargement (Fig. 7A). The lateral and oblique projections and barium swallow, however, showed an undisplaced esophagus outlining an apparently normal posterior cardiac contour and an enormous mass filling the antero-inferior

80

HOCHHOLZER,

THEXOS

AND

ROSEN

Fig. 7.-(AFIF’ Negative 60-6475-l and 6). Case 3. Huge anterior mediastfnal mass. A. This pre-employment chest examination of an 18 year old youth was interpreted as marked cardiac enlargement. An extensive evaluation and work-up, including catheterization, revealed no cardiac abnormality. Barium swallow outlined a normal posterior cardiac contour. B. Lateral projection. The mass fills the anteroinferior mediastinum and the entire left lower thorax. Note that the mass has a bizarre shape and seems to slope down and spread over the entire left hemidiaphragm and rest against the posterior chest wall as if it were poured into place. mediastinum and the entire left lower thorax (Fig. 7B). The mass spreads out over the entire left hemidiaphragm and comes to rest against the posterior chest wall, as though it had been poured into place. This results in a pendulous formation of the mass, the upper surface of which seems to slope downward from an attachment higher in the mediastinum. The mass seems to have fallen of its OWII weight and “plopped” down on the diaphragm. The “molding” into the accessible chest space is apparently due to the softness of the lesion. This appearance is fairly characteristic of the entity to be described below. This is illustrated vividly in Figure 8, which is another example of this lesion observed over a 6 year period in a different patient, in which the mass seems to have fallen of its own weight as it slowly increased in size. Note that the right border of the heart is effaced (the silhouette sign at work! ) , indicating an anterior mediastinal location. CZinic~Z Data. Physical examination was normal except for dullness to percussion up to the level of T8 on the left and Tll on the right, and decreased breath sounds below the level of dullness on the left. EKG was normal, as was cardiac catheterization. At thoracotomy a huge tumor filled the anterior mediastinum and most of the left chest cavity, displacing the heart to the right and compressing the left lung but not attached to it. The tumor was densely adherent to the anterior pericardium and was dissected from the right parietal pleura with some difficulty. A vascular pedicle was seen running from the tumor to the region of the

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LESIONS

81

Fig. 8.-(AFIP Negatives 60-3050-l and 2). Another example of the same entity shown in Fig. 7. A. The bulge effaces the right heart border and indicates an anterior

mediastinal mass. B. Six years later. Note that the mass seems to have fallen of its own weight as it slowly increased in size. thymus gland. The consistency of the tumor was described as soft and somewhat fatty. Pathologic Findings. The tumor was described as an irregular, lobulated, encapsulated yellow mass, measuring 37 x 23 x 8 cm. and weighing 2960 Gm. Figure 9 shows the cut surface of a similar tumor from another patient and depicts the typical gross appearance. It presents a mottled surface composed of irregular yellow fatty areas intermingled with irregular, opaque, grayishwhite areas of firmer consistency. The former predominate. Figure 10 reveals that the tumor is composed of a disorderly admixture of thymic parenchymal tissue, adult adipose tissue, and connective tissue. The thymic parenchymal tissue lacks the normal lobular and corticomedullary pattern of the thymus gland at this patient’s age. Instead it presents a peculiar mixture of distorted patterns, apparently related to the intrusion of the fibrofatty component. Much of the thymic tissue consists of strands and islands of thymic epithelium and lymphocytes, in varying proportions, having the appearance of involuted or atrophic thymus gland. Other portions of the thymic parenchymal tissue consist of larger, more cellular areas, mostly lymphocytic, suggesting thymic cortical tissue or hyperplasia of thymic lymphocytes.

Fig. ,9.-(AFIP Negative 65-12571-1). Gross appearance of a tumor similar to that of Case 3. The cut surface is

mottled with irregular, soft, yellow fatty areas and firm opaque grayishwhite areas.

82

HOCHHOLZER,

THEROS

AND

ROSEN

Fig. IO.-((GFIP Negative 61-1994). Case 3. Low power photomicrograph of the tumor shows a disorderly admixture of thymic parenchymal tissue, adult adipose tissue, and

connective

tissue.

The former consists of strands of involuted thymus (dark). Many calcified

Hassall’s

corpuscles

are present. Other areas showed more cellular

thy-

mic parenchyma, suggesting hyperplasia.

Hassall’s corpuscles, often calcified, are numerous. The adipose and connective tissue often surround and widely separate strands of involuted or atrophic thymic parenchymal tissue and appear to invade the larger, more cellular islands of thymic tissue in a manner suggestive of an earlier stage of replacement. Pathologic

Diagnosis.

Thymolipoma. DISCUSSION

The tumor in this case is a typical example, both radiologically and pathologically, of thymolipoma,1°-12 a rare but distinct pathologic entity that must be included in the differential diagnosis of anterior mediastinal masses. It is a benign tumor whose capsule is that of the thymus gland itself. The tumor consists of an admixture of thymic parenchyma and fibroadipose tissue in varying proportions. Approximately 28 cases were found in the English liferature, and there are 10 cases of this entity in the AFIP files, 2 of which have been reported by others. The average age at discovery was 21; the youngest patient was 4 years old. A considerably higher incidence is recorded in males. Of the AFIP cases, 6 were males and 4 females. Clinically, the majority of patients were asymptomatic and the tumor was discovered on routine chest radiographs or as an incidental finding. Growth appears to be very slow and the tumor may be present for many years. When symptoms are present, they are due primarily to the mechanical effects of the tumor, their severity being roughly parallel to the size of the mass. As in our patients, these tumors may reach very large size, the largest one reported weighing 6,000 Gm. and measuring 34 x 30 x 10 cm. They are generally removed without much difficulty and do not recur or metastasize. Nor has myasthenia gravis occurred in any of the patients in spite of the more than normal amount of thymic tissue in the tumor and the histologic evidence of hyperplasia.

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LESIONS

As previously indicated the great size of some of these tumors and their softness, attributable to their large fat component, may lead to an unusual radiographic configuration (Fig. 7). It is curious, however, that despite the large amount of fat, these tumors seldom yield the translucent appearance so commonly observed on radiographs of Iipomas in other parts of the body, particularly the abdomen and pelvis. This can probably be ascribed to the fact that in the chest they are seen against the more radiolucent background of air-containing lungs and the effect is lost without the surrounding enveIope of “water” density. A review of the radiographs of most of the Iipomatous masses of the mediastinum in the AFIP files confirmed our inability to find even one good example in which we could confidently report increased radiolucency. The nature of this lesion is not clear, as is evident from the list of designations that have been applied to it, namely, benign thymoma, Iipoma of thymus, mediastinal lipoma with inclusion of remnants of thymus gland, lipothymoma, and thymolipoma. Tl~ynzolipoma, implying a mixed neoplasm of thymic parenchymal tissue and thymic fat, is the term most often used. In this hypothesis, it has been assumed that the large, often predominantly fatty or fibrofatty component represents a benign neoplastic overgrowth of the fat within the thymus gland. Since it has been estimated that the total amount of thymic parenchymal tissue in some, if not all, of these large masses far exceeds the weight of normal thymus glands, it has also been assumed that this represents a benign neoplastic overgrowth of thymic tissue. The thymic tissue is not histologically neoplastic, however. Much of it is of the involuted type. Some of the tissue, mostly the lymphocytic component but occasionally also the epithelial component, appears hyperplastic. These observations seem to support the hypothesis of involuting thymic hyperplasia, which assumes that the tumor is primarily a hyperplasia of thymic parenchyma with secondary involution and fat replacement, as normally occurs in the thymus gland with aging. Additional support for this hypothesis may perhaps be obtained from two cases in the AFIP files of youngsters 4 and 4% years of age with tumors weighing 860 Gm. and 120 Gm., respectively. The thymic parenchymal component was more abundant than in any of our 8 adult patients, and apparentIy exceeded the fatty component. Furthermore, the thymic tissue was largely cellular with considerable retention of the corticomedullary pattern, and there was only a small proportion of involuted or invoIuting thymic tissue. These findings were for the most part the reverse of those in adults. Perhaps, therefore, a designation such as Iipomatoid hyperplasia of thymus would be more accurate than thymolipoma. Still another plausible hypothesis, which apparently has not been aired in the literature but which was suggested in 1956 by Dr. LaIIa Iverson (formerly of the AFIP) is that of hamartoma ( thymolipomatous hamartoma ) . &SE 4 Radiologic Findings. Frontal and oblique views of the chest (Fig. 11) of a 49 year old man show a fairly large mass based in the middle mediastinum but extending toward the posterior mediastinum anterior to the vertebral column. The contour is irreguIar and poIycycIic, suggesting the most frequent cause

84

HOCHHOLZER,

Fig.

ll.-(AFIP

Negatives

59-6732-4

and 5). Case 4. Middle

THEROS

AND

mediastinal

ROSEN

mass.

Frontal and oblique views of the chest of a 49 year old man show a fairly large mass based in the middle mediastinum but extending toward the posterior mediastinum anterior to the vertebral column. The contour is irregular and polycyclic, suggesting the most frequent cause of masses in the middle mediastinum-enlarged lymph nodes resulting from an inflammatory or neoplastic process. of masses in the middle mediastinum-enlarged lymph nodes. The cause may be neoplasm ( primary or metastatic) , granuloma, or nonspecific inflammation. When the nodes are prominent, one may especially consider such entities as lymphoma, metastatic carcinoma (particularly undifferentiated bronchogenic carcinoma of the oat cell type), and sarcoidosis. The latter entity is not likely in the present case since the peribronchial nodes are not involved. When the mass of nodes extends into the lung fields as a continuous density from the mediastinum on the frontal view (Fig. llA), sarcoidosis and infectious granuloma are unlikely, and lymphoma and metastatic disease are the prime considerations. Actually, the present entity is seldom considered. Indeed, it usually results in nodal masses of more modest size and may occur in any part of the mediastinum where lymph nodes are located. Clinionl Data. This patient was entirely asymptomatic when the mass in the lower middle mediastinum was seen on a routine chest film. Physical examination revealed nothing pertinent; there was no peripheral lymphadenopathy. The operative report described a rounded, solid mass “in the posterior mediastinum anterior to the vertebral column and protruding into the right chest beneath the azygos vein.” Pathologic Findings. The tumor measured 9 x 7 x 5 cm. and weighed I70 Gm. It was tan to brown, bosselated, and surrounded by a delicate capsule. Cut section revealed homogeneous, firm, rubbery, gray to pink tissue (Fig. 12). IJnder low power the architecture was consistent with that of a lymph node (Fig. 13). There was, however, a marked increase in the number of follicles, which varied in size, and were distributed throughout the mass rather than

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85

LESIONS

IS.-(AFIP Negative Fig. 55-17467). Case 4. Cut section of the mediastinal mass showing a rather smooth homogeneous surface that was gray to pink. The tissue was firm and rubbery. The external surface was bosselated, accounting for the irregular polycyclic contour seen radiographically.

Fig. 13~(AFIP Negative 64-3726). Case 4. Low power photomicrograph shows a pattern consistent with that of a lymph node but with an unusually large number and diffuse distribution of lymph follicles. This follicular hyperplasia is one of the distinctive features of the lesion.

Fig. 14.-(AFIP Negative 68-1635). Case 4. Medium power photomicrograph shows a lymph follicle with a large, pale, germinal center that mimics a HasAl’s corpuscle and is occasionally responsible for a wrong diagnosis of thymoma. The striking proliferation of capillaries in the interfollicular tissue and the unusual penetration of the follicular center by thick-walled capillaries are other distinctive features of this lesion (“angiomatous” hyperplasia).

only

in the peripheral

cortical

zone, as in normal

lymph

nodes.

Under

higher

magnification (Fig. 14), a lymph follicle with a large germinal center and unusual penetration of the center by thick-walled capillaries was seen; the interfoIIicuIar tissue contained numerous proliferating vascular channels of capillary type with obliteration of sinusoids. The abundant capillaries were more sharply outlined by the PAS technic (Fig. 15) which also showed plump endothelial cells and thickening of capillary walls. Small numbers of plasma cells and eosinophils were present.

HOCHHOLZER,

I I

1

Pathologic

Diagnosis. Tumor-like

THEROS

AND

ROSEN

Fig. 15.-(AFIP Negative 68-1638). Case 4. A photomicrograph of a section stained by the PAS technic out-

lines the capillaries more sharply and shows thickening of their walls, especially in the follicular center (lower right). The endothelial cells are Plump*

hyperplasia

of a mediastinal

lymph node.

DISCUSSION This follicular and capillary proliferation is characteristic of an entity of unknown cause that we classify as tumor-like mediastinal lymph node hyperplasia13-lT and which appears in the literature under a variety of names, depending largely on which histologic features are most prominent and also upon the author’s concept of the nature of the lesion. Some of these synonyms are: localized mediastinal lymph anode hyperplasia resembling thymoma, angiofollicular lymph node hyperplasia, follicular lymphoreticuloma, and lymph nodal hamartoma. This lesion is sometimes incorrectly diagnosed as a thymoma, particularly when it is located in the anterior mediastinum and when the follicular centers bear some resemblance to Hassall’s corpuscles. These tumorlike lymph node masses are not confined to the mediastinum, however. They may occur in the hilar lymph nodes and even in peripheral lymph nodes. The patients are usually asymptomatic and the lesions are discovered on routine chest films. The masses vary in size from 3 cm. to as large as 16 cm. in diameter and are usually well circumscribed and encapsulated. In the clinical work-up of our own patient, the lesion was described as being located “in the posterior mediastinum.” The lateral chest film, however, shows that the mass is actually based in the middle mediastinum. This case illustrates that careful attention to the details of the radiographic patterns may narrow the gamut of possibilities. Forty-seven cases of this lesion of mediastinal lymph nodes are recorded in the literature and the AFIP files contain an additional 35. There is no significant difference in incidence between the sexes, The ages range from 8 to 58 years. Some of the lesions had been present with little or no change for several years (as many as 18 years in one reported instance), and there was no recurrence after removal in any of the cases, features attesting to their benign nature.

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87 CASE 5

Radiologic Findings. Frontal and lateral views of the chest of a 36 year old woman reveal a fairly large, lobulated, unilateral mass in the anterior mediastinum (Fig. 16). The anterior location again calls for consideration primarily of thymic and teratoid lesions or adenopathy. The moderate size and location and the presence of a “sulcus sign” strongly suggest a thymic lesion. As stated earlier, the sulcus sign is most often associated with moderate-sized thymic lesions. It is much less frequent with teratoid tumors. Lesions with the histologic label to be discussed here are often located higher in the anterior mediastinum than in the present case. They are, then, often associated with cervical adenopathy but seldom with visible involvement of the hilar or lower mediastinal nodes, Clinical Data. The patient was asymptomatic and the anterior mediastinal mass was discovered on a routine chest film taken in connection with her occupation of food handler. Physical examination revealed no significant findings. Significant laboratory data included: WBC, 13,400 with neutrophils 54, bands 4, lymphocytes 2Q, monocytes 3, and eosinophils 9; hematocrit was 35 per cent. Bronchoscopy and findings from a left scalene node biopsy were normal. Thoracotomy confirmed the presence of a large anterior mediastinal mass measuring 8 cm. in diameter. Pathologic Findings. The mass was firm, bosselated, and encapsulated. Remnants of thymic tissue were attached to the capsule in one area. On cross with varying-sized, section (Fig. 17) the tumor presented a nodular s&ace elevated, grayish-yellow nodules separated by depressed, grayish-white fibrous septa and resembled somewhat the pseudolobular pattern of a thymoma. Microscopically, the most distinctive feature are the multiple cellular nodules of varying size and composition, separated by bands’ of dense, collagenous

Fig. 16.-(AFIP Negatives 65-4098-l and 3). Case 5. Anterior mediastinal mass. Frontal and lateral chest films of a 36 year old woman show the mass to be unilateral, moderately large, and lobulated. Note in B the well-defined “sulcus sign” at its inferior edge where it is apposed to the sternum (compare with Fig. 4B). The findings suggest that a thymic lesion is a good possibility.

HOcHI-IOLZER,THEROSAND ROSEN

88

Fig. 17.-(AFIP Negative 59-7249-2). Case 5. Cut surface of the tumor presents a markedly nodular appearance with varying-sized grayish-yellow nodules separated by prominent grayish-white fibrous septa. fibrous tissue, the latter in some instances predominating over the former (Fig. 18). The pleomorphic cellular nodules are composed of varying proportions of lymphocytes, plasma cells, eosinophils, neutrophils, and large pleomorphic cells with abundant acidophilic cytoplasm and one or more nuclei, often with prominent nucleoli (Fig. 19). The prominence of the latter cells, which are interpreted as atypical reticulum cells, is a distinctive feature of the lesion. Typical Sternberg-Reed cells are often diflicult to discern, but acceptable ones can usually be found on careful search. Pathologic Diagnosis. Nodular sclerosing Hodgkin’s disease of anterior mediastinum. DISCUSSION Nodular sclerosing Hodgkin’s disease1s-21is now generally recognized as a special type of Hodgkin’s disease, although for a time those tumors located in the anterior mediastinum were believed by some to be a special type of thymoma (granulomatous thymoma) and are still occasionally so misdiagnosed. It appears to occur in a younger age group than other types of Hodgkin’s disease. The tumor usually presents as an encapsulated mass in the anterior or anterosuperior mediastinum and, in our experience, is often associated with remnants of thymus gland. It is believed, therefore, that it may arise in the thymus gland in the same manner that lymphosarcoma may. In some instances, however, there is involvement of mediastinal lymph nodes with or without

Fig. I&-(APIP Negative 68-6426). Case 5. Very low power photomicrograph of the tumor depicts clearly its most distinctive feature: multiple cellular nodules separated by broad bands of fibrous tissue.

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LESIONS

Fig. 19.-(AFIP Negative 6% 6425). Case 5. High power photomicrograph. A field in a cellular nodule shows the typical mixed cell population and the prominence of the large atypical reticulum celIs that is a characteristic of this disease. Sternberg-Reed cell with multiple nuclei and large prominent nucleoli is present at lower left.

demonstrabIe involvement of the thymus. Because of its distinctive morphologic features indicated by its name and because of its predilection for the anterior mediastinum (often with supraclavicular lymph node involvement), its tendency to remain localized, and its better prognosis with considerably longer survival than the usual granulomatous type of Hodgkin’s disease, it has been designated at the AFIP as a special type of Hodgkin’s disease and given the name nodular sclerosing Hodgkin’s disease. There have been few references to Hodgkin’s disease by this name in the literature. In the AFIP files, there are over 150 cases of nodular sclerosing Hodgkin’s disease, most of which involveo the anterior mediastinum. REFERENCES 1. Condon, W. B., Safarik, L. R., and Elzi, E. P:: Extramedullary hematopoiesis simulating intrathoracic tumor. Arch. Surg. 90:643, 1965. 2. Knoblich, R.: Extramedullary hematopoiesis presenting as intrathoracic tumors: Report of a case in a patient with thalassemia minor. Cancer 13:462, 1969. 3. Lowman, R. M., Bloor, C. M., and Newcomb, A. W.: Roentgen manifestations of thoracic extramedullary hematopoiesis. Dis. Chest 44:154, 1963. 4. Papavasiliou, C. G.: Tumor simulating intrathoracic extramedullary hemopoiesis: Clinical and roentgenologic considerations. Amer.J. Roentgen. 93:695, 1965. 5. Sorsdahl, b. S., Taylor, P. E., and Noyes, W. D.: Extramedullary hematopoie’ mediastinal masses, and spinal cord zmpression. J.A.M.A. 189:343, 1964. 6. Edland, R. W., Levine, S., Serfas, L. S., and Flair, R. C.: Seminoma-like tumor in the

hyperplastic thymus gland. A case report and literature review. Amer. J. Roentgen. 103:25, 1968. 7. Kleitsch, W. P., Taricco, A., and HasJam, G. J.: Primary seminoma ( germinoma ) of the mediastinum. Ann. Thorac. Surg. 4: 249, 1967. 8. Kountz, S. L., Connolly, J. E., and Cohn, R.: Seminoma-like (or seminomatous) tumors of the anterior mediastinum: Report of four new cases and a review of the literature. J. Thorac. Cardiovasc. Surg. 45: 289, 1963. 9. Steiumetz, W. H., and Hays, R. A.: Primary seminoma of the mediastinum: Report of a case with an unusual site of metastasis and review

of the literature.

Amer.

J.

Roentgen. 86:669, 1961. 10. Benton, C., and Gerard, P.: Thymolipoma in a patient with Graves’ disease: Case report and review of the literature. J. Thorac.

Cardiovasc.

Surg. 51:428,

1966.

90 11. Fredell, C. H., and Perlmutter, A. D.: Thymolipoma: Report of a case. Arch. Surg. 83:898, 1961. 12. Trites, A. E. W.: Thyrolipoma, thymolipoma and pharyngeal lipoma: A syndrdme. Canad. Med. Ass. J. 95:1254, 1966. 13. Castleman, B., Iverson, L., and Menendez, V. P.: Localized mediastinal lymphnode hyperplasia resembling thymoma. Cancer 9:822, 1956. 14. Jamplis, R. W., North, F. S., and Johnson, W. D.: Benign interlobar hyperplastic lymph node resembling thymoma. Arch. Surg. 83:894, 1961. 15. Tung, K. S. K., and McCormack, L. J.: Angiomatous lymphoid hamartoma: Report of five cases with a review of the literature. Cancer 20:525, 1967. 16. Veneziale, C. hl., Sheridan, L. A., Payne, W. S., and Harrison, E. G., Jr.: Angiofollicular lymph-node hyperplasia of

HOCHHOLZER,

THEROS

AKD

ROSEN

the mediastinum. J. Thorac. Cardiovasc. Surg. 47:111, 1964. 17. Wolfel, D. A., Antonius, J. I., and Cowley, R. A.: Posterior mediastinal lymph node hyperplasia. Amer. J. Roentgen. 91: 120, 1964. 18. Hanson, T. A. S.: Histological classification and survival in Hodgkin’s clisease: A study of 251 cases with special reference to nodular sclerosing Hodgkin’s disease. Cancer 17: 1595, 1964. 19. Lattes, R.: Thymoma and other tumors of the thymus: An analysis of IO7 cases. Cancer 15: 1224, 1962. 20. Lukes, R. J.: Relationship of histologic features to clinical stages in Hodgkin’s disease. Amer. J. Roentgen. 90:944, 1963. 21. Lukes, R. J., Butler, J. J., and Hicks, E. B.: Natural history of Hodgkin’s disease as related to its pathologic picture. Cancer 19:317, 1966.