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Mediastinum:
A Clinical, Radiologic, Cytologic,
and Histologic Study of 42 Cases
Nina S. Shabb, M.D.,1* Mehieddine Fahl, M.D.,2 Basem Shabb, M.D.,3
Patrecia Haswani, M.D.,1 and Ghazi Zaatari, M.D.1
428
Results
We had a total of 42 patients with an age range from 1072
yr and a mean of 41 yr (Table I). There were 25 males and 17
r 1998 WILEY-LISS, INC.
Age
and
sex
Lymphoma
Hodgkins
1
22 F
Symptoms
Location and
characteristics
of tumor
Size
(cm)
FNA
diagnosis
Pathology
diagnosis
Dyspnea and
cough
55 M None, routine
CXR
10
C/W Hodgkins
Hodgkins NS
C/W Hodgkins
1. Nondiagnostic
2. Hodgkins NS
32 F
C/W Hodgkins
Hodgkins NS
27 F
Ant. Solid,
invading chest
wall
Ant./superior,
solid
Ant. Solid,
invading chest
wall
Ant. Multiple,
invading chest
wall
Ant. Multiple,
invading chest
wall
C/W Hodgkins
Hodgkins NS
C/W Hodgkins
Ant. Solid,
invading chest
wall
Ant. Invading
chest wall
Dyspnea and
cough
Dyspnea and
cough
16 M Chest pain
38 M Chest pain
31 F
Chest pain
Non-Hodgkins,
LCL
8
56 F
Chest mass
10
11
30 M Dyspnea
17 M Shoulder pain
25 F Dyspnea and
cough
Non-Hodgkins,
lymphoblastic
12
13 M Cough
13
Thymoma
14
15
16
Germ-cell tumor
17
Surgical
procedure
Comments
Suprasternal
mediastinotomy
Both: mediastiFirst mediastinotomy
notomy; nondiagnostic
Mediastinotomy
Hodgkins NS
Cervical LN
biopsy
Mediastinotomy
S/O thymoma
1. Nondiagnostic
2. Hodgkins NS
Both: mediastinotomy
Nondiagnostic
Hodgkins NS
Mediastinotomy
LCL
LCL, diffuse
Cervical LN bx
LCL
No bx
None
Treated on FNA
result; surgery
avoided
Ant. Solid
Ant. Solid
8
LCL
No bx
Large 1. Malignant NOS 1. Hodgkins NS
2. Nondiagnostic 2. LCL
None
Both: mediastinotomy
Ant. Solid
Large Lymphoblastic
lymphoma
No bx
None
Lymphoblastic
lymphoma
No bx
None
Thymoma, noninvasive
Thymoma, invasive
Thymoma, noninvasive
Mediansternotomy
Mediansternotomy
Mediansternotomy
Surgical biopsy
avoided
Surgical biopsy
avoided
Surgical biopsy
avoided
10 M Cough
Ant. Solid
30 M Chest pain
Thymoma
Thymoma
2.5
Thymoma
Ant. Solid,
invading chest
wall
Ant. Solid and
cystic
Undifferentiated
tumor, GCT?
GCT, embryonal
and yolk sac
Mediastinotomy
Multiple lung
nodules
Large Undifferentiated
tumor, GCT?
GCT, embryonal
and choriocarcinoma
No bx
Mediastinotomy
High serum
markers
None
Multiple lung
nodules, high
serum markers
51 M SVC syndrome
dyplopia
60 M None, routine
CXR
34 M Chest pain
18
24 M Cough
19
25 M Cough
15
Treated on FNA
result; surgery
avoided
Treated on FNA
result; surgery
avoided
C/W GCT
429
SHABB ET AL.
Table I. (continued)
Disease
categories
Age
and
sex
Thymic carcinoid
20
58 F
Angiosarcoma
21
Malignant neoplasm
NOS
22
23
24
Metastatic tumors
Oat cell
25
26
27
Adenocarcinoma
28
29
30
Symptoms
Location and
characteristics
of tumor
43 M Dyspnea and
hemoptysis
50 F
None, routine
CXR
FNA
diagnosis
Pathology
diagnosis
Surgical
procedure
10
Nondiagnostic,
scanty
Thymic carcinoid
(atypical)
Mediastinotomy
12
Spindle-cell neoplasm
Multiple lung
nodules
Undifferentiated
carcinoma
Thoracotomy,
biopsy
Malignant NOS
Thoracotomy,
biopsy
LFU
Cytokeratin,
PLAP &
HCG
Cytokeratin, LCA,
PLAP, HCG
Cytokeratin,
PLAP, alpha
FP, LCA?
Ant. Solid
Malignant, favor
lymphoma
50 M Cough
Ant.
Ca/lymphoma
No bx
None
65 F
47 F
Cough
Not available
Ant. Solid
Ant.
No bx
No bx
None
None
57 M Chest pain
32 F None, routine
CXR
56 M Cough and
hemoptisis
Ant. Solid
Ant. Solid
Adenocarcinoma No bx
Adeno C/W breast No bx
None
None
Ant. Solid
7
5
Malignant NOS
Mediastinotomy
Post. Solid
Ant. Solid
Large Adenocarcinoma
10
No bx
None
Ca/lymphoma
P.D. carcinoma,
nonoat cell
Thoracoscopy
32
50 M Dysphagia
Post. Solid
Large Ca/lymphoma
Metastatic ca to
LN
Mediastinoscopy
33
51 M Not available
Ant. Solid
No bx
None
21 M Dyspnea
Ant./superior,
solid
No bx
None
Granulomas,
tuberculosis
Noncaseating
granulomas,
sarcoid
Mediastinotomy
Benign conditions
Granulomatous
disease
35
20 M Cough, shortness Ant. Cystic
of breath
36
40 F Cough
Ant. Cystic
2.5
Metastatic small
round-cell sarcoma
Necrosis and a
few giant cells
Large Granulomas
Comments
Angiosarcoma
35 M Intercapsular
pain
35 M Cough
Poorly differentiated
nonoat cell
31
56 M Dyspnea and
chest pain
430
Size
(cm)
Mediastinotomy
Revised FNA
reading: oatcell ca
Revised FNA
reading: oatcell ca
History of breast
ca
History of small
round-cell sarcoma of flank, 9
mo prior
FU c/w sarcoid
Age
and
sex
62 F
Extramedullary
hematopoeisis
38
39 F
Thymic cyst
39
Inconclusive
40
41
42
58 F
Symptoms
Location and
characteristics
of tumor
Size
(cm)
FNA
diagnosis
Pathology
diagnosis
Surgical
procedure
Dysphagia
Post. Solid
Multinodular
goiter
No bx
None
None, routine
CXR
Post. Solid
None, routine
CXR
Ant. Unilocular
cyst
Ant. Solid
Ant.
Ant.
60 F Dyspnea
72 M Not available
65 F Not available
Extramedullary
hematopoeisis
No bx
None
No bx
None
Large Nondiagnostic
?
Nondiagnostic
?
Nondiagnostic
LFU
LFU
LFU
None
None
None
Comments
aAnt.,
anterior; bx, biopsy; C/W, consistent with; Ca, cancer; CXR, chest X-ray; GCT, germ-cell tumor; LCL, large-cell lymphoma; LFU, lost to follow-up;
LN, lymph node; NOS, not otherwise specified; NS, nodular sclerosis; P.D., poorly differentiated; Post, posterior; S/O, suggestive of; SVC, superior vena
cava.
No. of cases
Percent
24
13
3
3
1
1
3
10
9
1
5
2
1
1
1
3
42
57
24
12
7
100
aGCT,
431
SHABB ET AL.
Table III. Overall Performance of FNAa
Disease category
and no. of cases
Adequate
Inadequate
Correct
Incorrect
6
5
3
3
0
1
3
1
1
0
0
1
0
0
5
5
3
3
1
0
0
0
1
3
0
0
9
1
0
0
5
1
4b
0
1
1
1
1
0
35
1
0
0
0
3
7
1
1
1
1
0
0
0
0
30
Primary neoplasms
Hodgkins, 7
Non-Hodgkins, 6
Thymoma, 3
GCT, 3
Thymic carcinoid, 1
Angiosarcoma, 1
Malignant NOS
Metastatic neoplasms
Carcinoma, 9
Sarcoma, 1
Benign conditions
Granulomas, 2
MNG, 1
EMH, 1
Thymic cyst, 1
Inconclusive, 3
Total, 42
aGCT,
Primary Neoplasms
Lymphoma
Hodgkins lymphoma. There were 7 cases of Hodgkins
lymphoma (HL). The mean age was younger than that
of the group, i.e., 31 yr compared to 41 yr. There were 4
females and 3 males. All the tumors were solid, and
4 had invaded the anterior chest wall. FNA was consistent
with Hodgkins disease in 5 of the 7 cases where ReedSternberg cells, a few classic ones but mostly variants,
were seen in a background of a mixture of inflammatory
cells; mature lymphocytes, a few eosinophils, plasma
cells, and histiocytes (Fig. 1). In case 6, the FNA was
misinterpreted as suggestive of thymoma. Review of the
slides showed that in reality the tumor was not sampled,
but the aspirate consisted of sheets of mesothelial cells,
a few groups of bronchial epithelial cells, and clusters of
histiocytes, along with scattered lymphocytes. The overall
cellularity was moderate to scant. The sheets of mesothelial cells, along with the clustered histiocytes, were
misinterpreted as the epithelial component of a thymoma
(Fig. 2).
A limited surgical biopsy in the form of a mediastinotomy
was performed in all 7 cases. In one case where the FNA was
432
Fig. 2. Sheets of histiocytes intermixed with a few lymphocytes, misinterpreted as thymoma (Papanicolaou stain, 400).
consistent with HD, the first mediastinotomy was nondiagnostic, yielding only fibrous tissue, fat, and a mixture of
inflammatory cells. The second mediastinotomy yielded
diagnostic material.
In all 7 cases the surgical biopsies revealed nodular
sclerosis HD.
Non-Hodgkins lymphoma. There were 6 cases of nonHodgkins lymphoma (NHL), 4 of large-cell lymphoma
(LCL), and 2 of lymphoblastic lymphoma (LL). The mean
age was younger than that of the group: 25 yr compared to
41 yr. The 2 patients with lymphoblastic lymphoma were
age 10 and 13 yr. There were 4 males and 2 females. All
tumors were solid, and two had invaded the anterior chest
wall. The FNA was consistent with NHL in 5 of the 6 cases
with proper subclassification. The aspirates were cellular,
showing mostly discohesive lymphoid cells with lymphoglandular bodies in the background. In the LCL cases the cells
were predominantly large with irregular nuclei, with or
Fig. 3. Lymphoblastic lymphoma. Discohesive lymphoid cells of intermediate size with bland, even chromatin and convoluted nuclear contours.
Lymphoglandular bodies are evident (arrowhead) (Papanicolaou stain,
400).
without nucleoli. In the cases of LL, the cells were intermediate in size with irregular nuclear contours, and bland,
even chromatin without conspicuous nucleoli (Fig. 3).
Mitotic figures and tingible body macrophages were also
seen. Immunophenotyping of these lymphomas was not
done.
Three patients were treated on the bases of the FNA
results. Two patients underwent surgical biopsy, confirming
the FNA diagnosis in both cases. One patient was lost to
follow-up.
Thymoma
There were 3 cases of thymoma. All were adult males with a
mean age of 47 yr. One patient had symptoms of myasthenia
gravis. Two tumors were solid, and one was solid and cystic.
The FNAs of all 3 cases were consistent with thymoma. The
smears were biphasic and composed of epithelial cells and
lymphocytes (Fig. 4). The epithelial cells were in large,
cohesive, mostly two-dimensional fragments, with some
smaller fragments and rare single cells. The cells had
abundant cytoplasm which was poorly defined. The nuclei
were round to oval, and occasionally spindled, and were
regular and small with bland chromatin. They were evenly
spaced within the fragments and did not overlap. Anaplasia
and mitosis were absent. The number of lymphocytes
intermingled with these epithelial fragments varied from
area to area in the same case and from case to case. The
lymphocytes were abundant and either lay on top of the
epithelial fragments or were scattered throughout the slide.
The lymphocytes were small and round, and appeared
mature. No other elements were seen.
A limited surgical biopsy was avoided in all 3 cases, and
the surgeon went directly to mediansternotomy and excision
of the tumor. In one case, however, the thymoma was
invasive and deemed inoperable; only a biopsy was taken.
Fig. 5. Germ-cell tumor. High-grade epithelial-type tumor cells (Papanicolaou stain, 400).
Germ-Cell Tumors
There were 3 cases of germ-cell tumors (GCT). All were in
adult males with a mean age of 28 yr. Two of the tumors
were mixed solid and cystic, while the other was purely
solid. In addition to the mediastinal masses, 2 patients had
multiple lung nodules. Serum markers (alpha-fetoprotein
and HCG) were elevated in 2 patients. FNA showed a
high-grade epithelial-type neoplasm in all 3 cases, which in
conjunction with the serum markers and the young age of the
patients made the diagnosis of GCT most likely on FNA
(Fig. 5). In one case, syncytiotrophoblasts were seen on the
FNA slide.
One patient was treated on the basis of the FNA. Two
patients had a limited surgical biopsy. In these cases the
biopsy showed mixed, nonseminomatous GCT.
Diagnostic Cytopathology, Vol 19, No 6
433
SHABB ET AL.
Angiosarcoma
This patient presented with a mixed solid and cystic anterior
mediastinum mass with multiple lung nodules. FNA showed
a monotonous population of spindle cells. The cells were in
densely cellular fragments composed of a single population
of monomorphic hyperchromatic spindle cells which lacked
cytologic atypia, pleomorphism, and mitotic figures. The
diagnosis was spindle-cell neoplasm; differential diagnoses
included spindle-cell thymoma (although a lymphoid component was lacking) and monomorphic sarcoma. Mediastinotomy and biopsy revealed an angiosarcoma. The tumor
cells were positive for factor VIII.
Metastatic Neoplasms
There were 9 metastatic carcinomas and one metastatic
sarcoma.
Six cases were of lung primary. In these cases the
mediastinal mass was so large as to obscure the origin from
the lung, or the mediastinal mass was dominant with a small
mass in the lung. FNA in 3 cases were small-cell undifferentiated (oat-cell) carcinoma, 2 were poorly differentiated
nonsmall-cell carcinoma, and one was adenocarcinoma.
One metastatic adenocarcinoma was from a breast primary. In 2 cases, the primary lesion was unknown. The
original reading on four of these FNAs was malignant
neoplasm, carcinoma vs. lymphoma. Review of these aspirates revealed features of carcinoma in all four.
Benign Conditions
Granulomatous Disease
There were 2 cases in this category. The first (case 35) was a
20-yr-old man who had by radiologic and clinical impression an aggressive invasive lesion in the anterior mediastinum. FNA yielded necrotic material and a few giant cells. At
surgical exploration the lesion was found to be poorly
circumscribed, with invasive margins. Frozen section revealed caseating granulomas. Tissue culture later grew
Mycobacterium tuberculosis. The second case (case 36) was
a 40-yr-old woman who had enlarged anterior mediastinal
lymph nodes. FNA showed well-formed, noncaseating granu434
Multinodular Goiter
This 62-yr-old woman (case 37) presented with dysphagia.
Her past medical history was significant for partial thyroidectomy 10 yr prior to her presentation. A CT scan showed a
well-defined solid mass in the posterior mediastinum, 3 cm
in size. FNA showed many large open sheets of follicular
epithelium in honeycombed arrangement, with smaller colloid-containing follicles, a few histiocytes, and colloid
material in the background (Fig. 7). Further radiologic
studies showed a thin band of tissue connecting this mass to
the anterior neck. Iodine uptake studies were positive,
proving the true thyroid nature of the lesion.
Fig. 8. Extramedullary hematopoeisis. Two megakaryocytes in a background of erythroid and granulocytic precursors (Papanicolaou stain,
400).
Extramedullary Hematopoesis
This 39-yr-old woman, already diagnosed with congenital
dyserythropoetic anemia, presented with complaints related
to severe anemia. In addition to low hematocrit and heart
failure, she had a well-defined, solid, 3-cm mass in the
paravertebral area in the posterior mediastinum. FNA revealed a mixture of hematopoetic elements, including many
megakaryocytes, granulocytes, and erythrocytes (Fig. 8). A
diagnosis of extramedullary hematopoeisis was made, and
the patient was saved a surgical procedure.
Thymic Cyst
In this case, the FNA yielded 50 cc of clear fluid. The cyst
disappeared after the aspirate. The FNA in this case was both
diagnostic and therapeutic.
Discussion
Although the role of FNA in the mediastinum remains
controversial,14,6,8,9 our results have shown that despite the
cystic, necrotic, and fibrotic nature of many of these lesions,
the tissue adequacy by FNA was remarkably good (83%),
and that despite the varied pathologic entities and the
difficulty in reaching a correct diagnosis even in open
surgical biopsies, our diagnostic accuracy by FNA was 86%.
The patient demographics in this study are similar to those
in previously reported series,1,4,14 with a wide age range
(1072 yr) and a male predominance (60%).
In contrast to similar previously reported data,1,4 our study
had a predominance of primary mediastinal lesions (57%),
while metastatic tumors accounted for only 24%. Other
similar reports have a predominance of metastatic tumors in
their series. This discrepancy is explained by our study
design. The aim of the study was to assess the dignostic
accuracy of FNA in primary mediastinal lesions; hence,
those cases that were obviously metastatic to the mediastinum were not included.
Many reports in the literature attest to the difficulty in
diagnosing and accurately distinguishing between thymomas and lymphomas by FNA alone, and recommend the use
of core-needle biopsy in these cases.2,4,8,15 In our study, these
cases were readily diagnosed by FNA alone. Ten of the 13
lymphomas and all 3 of the thymomas were correctly
diagnosed. Hodgkins disease of the mediastinum is usually
of the nodular sclerosis subtype, where dense fibrosis may
interfere with good cellular yield, and the paucity of classic
Reed-Sternberg cells may make the diagnosis by FNA
difficult. Despite the above-mentioned difficulties, 5 of the 7
cases of Hodgkins lymphoma yielded good cellularity, and
the diagnosis was suspected not on finding classic ReedSternberg cells, but on finding Reed-Sternberg variants in
the appropriate cellular background of inflammatory cells.
As is well-known, a definitive diagnosis of HL should not be
made on FNA alone. Confirmation needs to be obtained by
surgical biopsy. The advantage of FNA in these cases is that
the surgeon would know that he or she is dealing with a
lymphoma and can plan for a limited surgical procedure.
Non-Hodgkins lymphoma of the mediastinum is most
often diffuse large-cell or lymphoblastic.19,20 Smears are
usually cellular and composed of dispersed single cells with
lymphoglandular bodies in the background. The distinction
between the two subtypes is made on the cytologic details of
the cells, taking into account cell size, nuclear contours,
shape, and chromatin pattern. Tingible body macrophages
and many mitotic figures are seen more often in high-grade
lymphoblastic lymphoma.20
In this study, all cases of thymoma had the classic
biphasic pattern of bland epithelial cells in a background of
mature lymphocytes, and hence did not raise diagnostic
difficulties. This may not always be the case, since spindlecell thymomas and heavily lymphocytic thymomas may
indeed be problematic by FNA. In this study, one case (a
Hodgkins lymphoma) was incorrectly suspected of being a
thymoma. The aspirate was scanty and was not representative. Sheets of benign mesothelial cells and aggregates of
histiocytes were misinterpreted as the epithelial component
of a thymoma, while a few lymphocytes were interpreted as
the lymphocytic component. Similar difficulties have been
reported in the literature.1 The diagnosis of thymoma should
only be made when there is adequate cellularity in addition
to the typical biphasic pattern.
The distinction between poorly differentiated carcinoma
and lymphoma was not made in 4 of our cases. These were
called malignant neoplasms, lymphoma vs. carcinoma.
These cases were from the early part of the study, where the
limited expertise and confidence of the pathologist may have
played a role. Review of these cases showed typical cell
clustering, nuclear molding, nuclear variability, and hyperchromasia typical of carcinoma. The absence of lymphoglanDiagnostic Cytopathology, Vol 19, No 6
435
SHABB ET AL.
2. Rosenberger A, Adler O. Fine-needle aspiration biopsy in the diagnosis
of mediastinal lesions. AJR 1978;131:239242.
References
19. Stickler JG, Kurtin PJ. Mediastinal lymphoma. Semin Diagn Pathol
1991;8:313.
436
20. Jacobs JC, Katz RL, Shabb N, El-Naggar A, Ordonez NG, Pugh W.
Fine needle aspiration of lymphoblastic lymphoma: a multiparameter
diagnostic approach. Acta Cytol 1992;36:887894.