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2492
Malignant Fibrous Histiocytoma of the Lung
Report of Four Cases and Review of the Literature
Michele Y. Halyard, M.D.
John K. Camoriano, M.D.
John A. Culligan, M.D.
Louis H. Weiland, M.D.
Mark S. Allen, M.D.
James R. Pluth, M.D.
Peter C. Pairolero, M.D.
Mayo Clinic Scottsdale, Scottsdale, Arizona.
BACKGROUND. Primary malignant fibrous histiocytoma (MFH) of the lung is a rare
clinical entity. Only 23 reports of 49 cases have been reported in the literature.
Surgery was the primary mode of therapy, with high rates of local and distant
recurrence reported. The role of radiation therapy and chemotherapy has never
been clearly defined.
METHODS. The records of the Mayo Clinic in Scottsdale and Rochester from 1970
to 1990 were reviewed for cases of primary pulmonary MFH. A review of the
literature was also undertaken.
RESULTS. Four cases from the Mayo records and 49 cases from a review of the
literature were identified. Eight patients were alive at 5 years from diagnosis; all
had been treated with surgery as the primary modality. No definite relationship
between histologic subtype of MFH and survival could be identified and no definite
role of radiation therapy or chemotherapy could be defined.
CONCLUSIONS. MFH of the lung should be treated by surgical resection if technically feasible. The role of adjuvant therapy remains undefined. Cancer 1996;
78:2492-7. 0 1996 American Cancer Society.
KEYWORDS soft tissue neoplasms, histiocytoma, fibrous, surgery, thoracic neoplasms.
Address for reprints: Michele Y. Halyard, M.D.,
Mayo Clinic Scottsdale, 13400 East Shea Boulevard, Scottsdale, AZ 85259.
Received July 8, 1996; accepted August 5,
1996.
8 1996 American Cancer Society
Case 1
A 51-year-old female presented with a several-month history of pleuritic chest pain, shortness of breath, and cough. Earlier chest roentgenograms revealed progressive enlargement of a left lower lobe mass
from 3 to 5 cm over a 2-month period. At the time of presentation,
the chest roentgenogram and a computed tomography (CT) scan of
the chest and abdomen showed a 10 cm X 8 cm mass extending from
2 cm below the carina to the diaphragm, causing inferior displacement of the diaphragm (Fig. 1). A large pleural effusion was also
present, the cytology of which was negative for malignant cells. The
lesion contained a small amount of calcium. Physical exam and a CT
scan extending from the chest to the upper abdomen failed to reveal
any evidence of a primary site originating elsewhere.
A left lower lobectomy removed a well circumscribed, encapsulated tumor that measured 12 cm in greatest dimension. The tumor
was firm, partially myxoid, and contained areas of hemorrhage and
necrosis. Calcification was noted in the periphery of the tumor. The
overlying pleura was intact with the exception of a small area of
diaphragmatic invasion. This area was resected with the lower lobe.
Microscopically, the tumor was comprised of a spindle cell proliferation without appreciable differentiating qualities (Fig. 2). Mitotic figures were present, and focally there was a typical storiform pattern.
MFH of Lung: Cases and Literature Review/Halyard et al.
2493
FIGURE 1. Chest roentgenogram and computed tomography of a left lower lobe malignant fibrous histiocytoma.
B y iinrnunoperoxidase stains, the tumor was positive
tor vimeritin. but negative for keratin, S-100 protein,
and tle.sinin. The features by routine microscopy and
special 5tains were typical of malignant fibrous histiocytoma ( M F I I ) . ‘I’he hilar lymph nodes and margins of
resectioi I were negative.
‘l’hr patient received 5040-centigray (cGy) postoprmtive rndiarion to the middle and lower left thoracic
cavity. She developed radiation pneumonitis, which
was successfully treated with a short course of prednisone. The patient was without evidence of recurrence
in the chest, nor had another primary site become
manifest, 60 months after diagnosis.
Case 2
A 77-year-old man presented with an asymptomatic
pulmonary nodule in the middle lobe of the right lung
not seen on roentgenogram 4 years prior. CT scan of
the chest revealed a 1.3-cm indeterminate uncalcified
nodule and calcified left hilar lymph nodes. The nodule was observed but enlarged to 2.2 cm 4 months
later. Physical exam was unremarkable for evidence of
another primary site. A right middle lobectomy was
performed, and the lesion was found to be a poorly
differentiated, pleomorphic type, MFH. Paratracheal,
periesophageal, and subcarinal lymph nodes were
negative. The patient received no adjuvant therapy
and was without evidence of local or distant recurrence 36 months after diagnosis.
Case 3
A 38-year-old male presented with a history of an
asymptomatic left lower lobe nodule on chest roentgenogram previously removed elsewhere by wedge resection and termed “benign histiocytic tumor.” Upon
pathologic review, the lesion was found to be a poorly
differentiated MFH of the storiform type. There was
no evidence of another primary site at that time. Two
years later he developed cough, pain in the left posterior rib cage, weight loss, fatigue, headache, and an
elevated sedimentation rate. Chest roentgenogram
and CT scan revealed a 9-cm mass in the left lung base,
extending to the diaphragm, without intraabdominal
involvement. A 2-cm axillary mass, not present at the
2494
CANCER December 15,1996 / Volume 78 I Number 12
left upper lobe. N o other primary sites of disease were
identified. Resection of the brain metastasis and the
lung lesion were performed. The lung lesion invaded
the chest wall and measured 7.5 cm X 6 cm X 4 cm.
Pathology revealed both lesions to be poorly differentiated, storiform type MFH. Two of five intrapulmonary
lymph nodes contained metastatic disease. Three
weeks later, aspiration of a fluid collection in the right
parietal area revealed hemorrhagic, poorly differentiated sarcoma. The patient died within several days of
transtentorial herniation.
DISCUSSION
FIGURE 2. Typical malignant fibrous histiocytoma featuring spindle cells
in a storiform pattern (magnification X250).
initial time of diagnosis, was excised which was consistent with metastatic disease. A completion left lower
lobectomy was performed with subtotal resection of
the mass, which measured 11 cm X 9 cm X 8 cm. The
tumor invaded the visceral pleura and diaphragm. One
month later, the patient developed multiple chest wall
nodules and another axillary recurrence and received
1200-cGy external beam radiation to the left axilla.
Despite systemic chemotherapy, his disease progressed in the chest, abdomen, and axilla. Repeat CT
scan revealed extension of the mass into the abdomen.
The patient died 30 months after initial diagnosis.
Case 4
A 57-year-old female presented with ataxia, headache,
and left homonymous hemianopsia. CT scan of the
head showed a large cystic mass in the right frontoparietal region, displacing the ventricular system to the
left. There was enhancement of the wall of the cyst,
with a mural nodule on the medial surface. Chest
roentgenogram revealed a 7-cm cavitating mass in the
Soft tissue sarcomas are neoplasms that arise largely
in mesodermal structures. MFH is the most common
soft tissue sarcoma in adults, usually arising in the
extremities or trunk. Metastasis to the lung is not an
infrequent occurrence. Primary MFH arising of the
lung is a rare clinical entity. There must be no evidence
of another primary site as determined by careful physical exam and radiologic evaluation before an MFH
can be considered as a lung primary rather than as a
metastatic lesion. In the current series, three of the
patients showed no evidence of another primary lesion
at the time of initial presentation. One patient presented with a solitary nodule in the lung and a metastatic lesion in the brain. As in the other three patients,
there was no evidence of another primary site.
A review of the English literature revealed only 49
reported cases of primary MFH originating in the lung,
excluding those arising from pulmonary arteries and
pleura (Table 1). Several additional cases have been
reported in the European and Asian literature as
we]].15.24-213 The origin of these tumors is not certain,
although a histiocytic origin with fibroblastic differentiation is postulated. The histiocytic features of primary malignant fibrous histiocytomas of the lung have
been reported to be similar to their counterparts arising elsewhere.
The median age of these patients, including those
in the current series, was 55 years, with a range of
10-80 years. Pediatric cases have been d e s ~ r i b e d . ’ ~ ~ ~ ~
Female predominance has been suggested, but a review of the literature revealed 30 male and 23 female
patients. The majority of the patients presented, as did
one of the current study patients, with chest pain and
dyspnea. Cough, weight loss, hemoptysis, and fatigue
were also commonly observed. Hypertrophic pulmonary osteoarthropathy, pulmonary thromboembolism,
hypoglycemia, and neutrophilia are less common presenting problems.8,”~’9
As observed in the current series, patients may be asymptomatic at presentation.
Radiographically, primary MFH of the lung tends
to be large, solitary, noncavitating, and peripheral,
MFH of Lung: Cases and Literature Review/Halyard et al.
2495
TABLE 1
Malignant Fibrous Histiocytoma of the Lung: Literature Review
Series
Age
Sex
Bedrossian et al.'
51
M
Kern et al.'
Chowden er al:'
Sajjad et al.'
Paulsen et al.'
\fills et al,"
Sritiinpai er a].'
hfisra et a]."
Larsen et 31.''
Lee et al.'"
Lessel and Ilrhstosser"
Silverman and Coalson"
Tanino et al.'"
McDonnell et al."
Ilsitt et al.'..'
luettner et d'"
Ismailer et a1.lYousem anti Hoccholzer'"
Case\. and Peddle'9
Palmer et iil.'"
White et al."
Reifsnyder et al."
hfarrhan et a]."
Present series
53
52
65
53
60
41
45
75
62
54
69
62
67
35
56
75
73
71
58
68
12
54
33
59
73
64
42
57
80
74
18
46
52
52
74
69
40
hl
F
F
F
F
M
M
M
M
M
h4
F
M
F
M
M
F
F
M
M
F
F
M
M
F
M
F
F
M
M
M
F
F
F
F
F
F
71
hl
19
63
36
32
21
46
62
55
58
10
5s
77
38
57
M
M
hZ
M
M
M
F
M
M
F
F
M
M
M
Site
LLL
RML
RLL
RLL
RML
LLL
RLL
RLL
RLL
RUL
LLL
LUI.
RUL
LLL
LUL
RLL
LUL
LUL
LLL
RUL
RLL
LLL
RUL
RLL
RUL
RLL
LUL
RUL
LLL
RUL
LUL
LUL
RLL
RUL
RLL
LUL
RUL
RUL
LLL
RML
LUL
LLL
RLL
LLL
RUL
LLL
RLL
RUL
RLL
LLL
LLL
RML
LLL
LUL
Sue (cm)
Histology
Surgery
Radiationlchemotherapy
5-FU (mos)
2
Storiform
Lobectomy
Biopsy
Lobectomy
No
DOD 14
No
Chemotherapy
Chemotherapy
No
No
No
Radiation
DUD 12
DOD 4
DOD 5
DOD 36
ALVD 18
DOD 18
DOD 10
NED 10
NED 12
DOD 7
NED 8
KED 120
NED 60
DOD 12
AWD 3
DOD 5
DOD 3
NED 10
DOD 12
DOD 12
AND 12
NED 108
NED 84
NED 65
NED 36
NED 16
NED 122
DNED 1
DEED 1
DOD 2
1)OD
DOD 8
DOD 9
DOD 72
DOD 24
DOD 36
DOD 24
DOD 8
DOD 14
DOD 14
DOD 12
DOD 3
NED 96
KED 8
DOD 14
DOD 4
Unk
Unk
NED GO
NED 36
DOD 30
DOD 1
4
8
5
11.5
4
10
9
16
2.5
6
7
8
5
4
25
8
5
6.5
5
5.5
20
9
1.7
3.8
5.9
8.5
5
3
4
3
Unk
10
6
Unk
4
14
8
4
Unk
Unk
7
3
11
3
10
Unk
Unk
5.5
5
12
2.2
I1
7.5
Stori-Pleo
Pleomorphic
Storiform
Storiform
Pleomorphic
Storiform
Storiform
Storiform
Stori-Plea
Stori-Plea
Stori-Plea
Stori-Pleo
Stori-Pleo
Stori-Pleo
Myxoid
Storiform
Stori-Pleo
Storiform
Storiform
Stori-Pleo
Storiform
Stori-Pleo
Stori-Pleo
Stori-Pleo
Stori-Plea
Stori-Pleo
Stori-Pleo
Stori-Pleo
Stori-Plea
Stori-Pleo
Stori-Pleo
Stori-Pleo
Stori-Pleo
Stori-Plea
Stori-Pleo
Stori-Pleo
Inflammatory
Stori-Pleo
Myxoid
InflammatoqI
Stori-Pleo
Stori-Pleo
Stori-Pleo
Unk
Storiform
Storiform
Unk
Unk
Storifom
Pleomorphic
Storiform
Storiform
NO
Pneumonectomy
Lobectomy
Lobectomy
Lohectomy
Biopsy
Wedge
Lobectomy
Biopsy
Pneumonectomy
Lohectoniy
Lobectomy
Biopsy
Biopsy
Autopsy
Lohectomy
Lobectomy
Lohectomy
Biopsy
Lobectomy
Lohectomy
Lohectomy
Lohectomy
Pneumonectomy
Lohect omy
Lohectomy
Pneumonectomy
Lobectomy
Biopsy
Lohectomy
Lobectomy
Biopsy
Lobectomy
Lohectomy
Biopsy
Lohectomy
Biopsy
Lobectomy
Biopsy
Excisional biopsy
Pneumonectomy
Lobectomy
Lohectomy
Lobectomy
Biopsy
Lohectomy
Lobectomy
Lohectomp
Lobectomy
Excisional biopsy
Lohectomy
NO
No
Chemotherapy
Radiation
Radiation
No
No
Chemotherapy
No
NO
No
No
No
No
No
No
NO
No
Radiation
No
No
No
KO
No postop
Radiation
Chemotherapy
Radiationichemotherapy
NO
Radiation
Radiation
Radiation
Radiationichemotherapy
No
No
Radiationichemotherapy
No
No
No
NO
No
No
Radiation
No
No
NO
1.Y: lymph nodes; 5-FU: 5-fluorouracil; Ivl: male; F: female; LLL: left lower lobe; R M L right middle lobe; R1.L right lower lobe; RUL: right tipper lobe; LUL left upper lobe: Unk unknown: Stori-Pleo: storiformuleomoruhic; Keg: neeatire; Pos: oositive; DOD: dead of disease; A W D alive with disease; N E D no evidence of disease; DNED: dead, no evidence of disease.
2496
CANCER December 15,1996 / Volume 78 / Number 12
with a slight preponderance to occur in the middle
and lower lobes. Pleural plaques have also been described in association with the dominant massz2Unlike the first case in the current study, calcification of
the lesions has not been described in the adult literature, but has been described in a pediatric case by
lsmalier et aI.l7 These tumors appear on CT to be of
soft tissue density, sometimes with areas of low attenuation centrally. Approximately 20% of patients have
an associated pleural effusion.'2
The microscopic features of MFH of the lung are
those of a malignant spindle cell neoplasm. Specific
microscopic characteristics are generally lacking, and
MFH can have histologic similarity to other soft tissue
neoplasms. Likewise, satisfactory specific immunohistochemical stains for MFH do not exist. However,
other soft tissue sarcomas, with microscopic similarity
to MFH on routine stains, can be excluded with immunohistochemical stains that do have specificity. Thus,
immunohistochemical stains for desmin, actin, and
stains for neurogenic tumors are generally used in the
laboratory examination of these tumors. As described
by Weiss and Enzinger, storiform, pleomorphic, myxoid, inflammatory, giant cell, and angiomatoid variants may occur." The majority of the primary lung
tumors are of the storiform variety.
Forty patients underwent gross total resection either by excisional biopsy, wedge resection, lobectomy,
or pneumonectomy. Of the 23 patients undergoing definitive resection who ultimately died of disease, the
median survival was 12 months with a range of 1 to
72 months. Seventeen resected patients were reported
to be alive without evidence of disease with a median
survival of 60 months (range, 8-122 months). Two patients were alive with disease at 12 and 18 months,
respectively, whereas 2 patients died without evidence
of disease recurrence within 1 month of resection. Of
those 11 patients who underwent biopsy only and died
of disease, the median survival was 9 months (range,
2-36 months).
Some reports suggest that long term survivors are
rare. The current literature review revealed 8 patients
alive without evidence of disease more than 5 years
after diagnosis, including the authors' 1 long term survivor, who was alive 60 months after diagnosis. A gross
total resection of the primary tumor was performed in
all eight patients. Eight patients were alive with a short
reported follow-up of 8 to 36 months. Of the patients
who died of their disease, the survival ranged from 1
to 72 months, with a median survival of 10 months. No
definite relationship between survival and histology
could be identified because of the predominance of
the storiform subtype. The authors' 2 survivors, as well
as those reported in the literature, all had negative
lymph nodes with the exception of 1 patient alive at
36 months despite mediastinal adenopathy.","','"'""
Systemic metastases are not infrequently reported. As
in the current series, the brain is a common site of
metastasis.2.4.8
17.20
According to White et al. this may
be due to a high incidence of vascular invasion by
these tumors observed in at least 50% of patients."
Radiation therapy has not commonly been used in the
treatment regimen. One of the current study patients
experienced long term control with adjuvant radiation.
The 10-year survivor reported by Lee et al. received
5400-cGy preoperative radiation therapy.'" However,
the role of radiation has not been defined. Systemic
chemotherapy has been used largely for metastatic
disease. Of the eight patients treated with chemotherapy as definitive or adjuvant treatment, no patients
were long term survivors. Drugs used for treatment
included doxorubicin, dacarbazine, cyclophosphamide, vincristine, and cisplatin. No series reported the
response to chemotherapy in which measurable disease was present.
The natural history of soft tissue sarcomas of the
extremities, including the MFH variety, is better
known due to greater numbers of reported cases.
These tumors are surrounded by a pseudocapsule that
allows infiltration of surrounding tissues into adjacent
tissue. Marginal en bloc excision of these tumors can
result in a local recurrence rate of 70-9070, whereas
even wide local excision results in a local recurrence
rate of approximately 50-70%.2RAlthough amputation
and radical local excision result in a low local recurrence rate of 5%," limb salvage with more conservative
surgery and radiation has increased in prevalence. The
less radical surgery is commonly preceded or is followed by radiation therapy to enhance local contr01.2Y."OInvolvement of lymph nodes occurs in approximately 5% of patients.'" Metastasis to the lung is not
an infrequent occurrence, occurring in 30-50% of high
grade lesions.3zThe majority of patients who develop
metastatic disease do so within the first 5 years of
diagnosis, as is the case with primary MFH of the lung.
Five-year survival is highly dependent on the tumor
grade. Results varied from 95% for Grade 1, 86% for
Grade 2, and 50% for Grade 3 tumors in a series by
Jensen et al.33The value of systemic chemotherapy in
these tumors is not yet definitely known, its role being
limited to those patients with a poor prognosis including large tumor size, high grade, or metastatic disease.
SUMMARY
In summary, MFH of the lung is a rare clinical entity
with variable outcome. Long term survivors have been
reported, yet many patients have died of their disease.
MFH of Lung: Cases and Literature Review/Halyard et al.
Aggressive surgery remains the mainstay of treatment.
The role of adjuvant remains undefined.
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