Romanian Journal of Morphology and Embryology 2009, 50(3):481–485
C CA AS SE E R RE EP PO OR RT T
Malignant fibrous histiocytoma of larynx with
giant cell: case report and histological-clinical
FL. ANGHELINA1), ELENA IONIŢĂ1), LUMINIŢA CHIUŢU2),
CARMEN AURELIA MOGOANTĂ1), S. CIOLOFAN1),
CRISTINA IOSIF3), M. CEAUŞU3)
2)Department of Anesthesiology
University of Medicine and Pharmacy of Craiova
3)Department of Pathology, “Victor Babeş” National Institute
for Research and Development in Pathology and
Biomedical Sciences, Bucharest
Introduction: Malignant fibrous histiocytoma (MFH) is a tumor which has a mesenchymal origin, and an uncertain histogenesis. MFH with
giant cell accounts for 3–15% of all malignant fibrous histiocytomas. Objective: To explore the histopathology, the diagnosis and the
treatment of MFH with giant cell of larynx. Patient and Methods: We report a case of a glottic MFH at a 59-year-old male, who has been
smoking for 30 years, and was hospitalized in June 2008 at Emergency County Hospital of Craiova. Results: The largely-sized tumor was
originated in glottic area, upper a left vocal cord, with no paresis. The tumor determined respiratory failure and dysphonia. Patient
underwent surgical excision of the tumor after an emergency tracheotomy. The immunohistochemical techniques proved positive for
vimentin, smooth muscle actin, CD68, CD34, bcl2, EGFR, S100, Ki67, and negative for CD117, NFT, chromogranin, c-erbB2,
CK34betaE12, MNF116, and p53. Conclusions: Malignant fibrous histiocytomas (MFH) with giant cell of larynx are very rare mesenchymal
neoplasm (this case seems the first reported). The diagnosis of MFH of larynx was difficult and the immunohistochemistry could have been
Keywords: malignant fibrous histiocytoma, larynx, giant cell, CD68, vimentin, smooth muscle actin (SMA).
Malignant fibrous histiocytoma (MFH) is a tumor
which has a mesenchymal origin and an uncertain
histogenesis and it is mainly found in the limbs, the
abdomen and the retroperitoneum [1, 2].
The term MFH is used to describe a histiocytic-like
tumor with fibrous tissue .
Histologically, there are five subtypes of MFH .
The histological diagnosis is based on the
proliferation of neoplasic cells (fusiform and polypoid)
that look like fibroblasts and histiocytes, with aberrant
atypias and mitosis. They are organized in bundles
with a variable pattern. It is difficult to establish a
correct differential diagnosis
histological techniques and, in order to be sure we
need confirmation from immunohistochemistry to
distinguish it from other tumors with mesenchymal
differentiation [5, 6].
We have studied a very rare case of malignant
fibrous histiocytoma of larynx, with giant cell variety.
? Patient, Methods and Results
We report a case of a glottic MFH with giant cell.
59-year-old male patient, who has been smoking for
30 years, was hospitalized in June 2008 at Emergency
County Hospital of Craiova. He had had hoarseness for
six months and progressive dyspnea for a month. While
undergoing indirect laryngoscopy we discovered a
globular, red-violaceous, pseudopolypoid lesion on
medium third of vocal cord on the left side, with
ulcerated epithelial cover, with no vocal cord paresis,
having a diameter of approximately 15 mm. There was
no palpable cervical lymphadenopathy. Biological tests,
neck echography and pulmonary radiography were
Initially, we had performed an emergency
tracheotomy due to severe respiratory failure. After the
tracheotomy, we performed a direct microlaryngoscopy
with excision of the tumor (Figure 1), and with closure
of tracheotomy in next step.
The tumor was fixed in 10% formalin solution and
wax embedded. The lesion was morphologically studied
with Hematoxylin–Eosin stain. The histopatho-logical
study showed a malign proliferation with spindle cell
proliferation with whorl pattern beneath the epithelium
(Figure 2) and many multinucleated giant cells
placed among fusiform cell fascicules (Figures 3–5).
We noticed the appearance of frequent atypical and
typical mitoses (Figure 6) and of small necrosis zones.
Fl. Anghelina et al.
performed using vimentin, smooth muscle actin, CD68,
CD34, bcl2, EGFR, S100, Ki67, CD117, NFT,
chromogranin, c-erbB2, CK34betaE12, MNF116, p53
antibodies (DAKO) and Streptavidin–Biotin method
(LSAB Kit, DAKO).
Vimentin (VIM) was positive diffused immunohisto-
chemical stain in spindle tumoral cells (Figure 7).
The histiocytic marker CD68 was positive in large and
giant tumoral cells (Figure 8). S100 was variable
positive in spindle-shaped cells (Figure 9). Smooth
muscle actin (SMA) was positive in medium-sized
vessels within the tumor mass (Figure 10), and focally
positive in spindle cells (Figure 11). CD34 was positive
in numerous vessels and negative in tumor (Figure 12).
Bcl2 was rare positive in tumoral cells. EGFR was
positive in blood vessels and negative in tumor cells
(Figure 13). Ki67 was positive in about 30–40% of
tumor cells nuclei (Figure 14). The immunohisto-
chemical techniques proved negative for CD117, NFT,
chromogranin, c-erbB2, CK34betaE12, MNF116, and
p53. The patient refused our proposal to undergo a
partial laryngectomy. The evolution in the following
two months did not show any recurrences.
Figure 1 – Spindle cell proliferation with whorl pattern
beneath the epithelium (HE stain, ob. 4×).
Figure 2 – Dense cellular area with plump ovoid to
spindle shape cells with prominent nucleoli (HE stain,
Figure 3 – Area with a variety of spindle, ovoid and
large cells, showing nuclear atypia and pleomorphism
(HE stain, ob. 10×).
Figure 4 – Spindle shaped cells with marked nuclear
atypia and pleomorphism (HE stain, 10×).
Figure 5 – Multinucleated giant cell in a dense mass of
round-ovoid and spindle cells proliferation (HE stain,
Figure 6 – Diffuse immunohistochemical stain for
vimentin in spindle tumoral cells (IHC, ob. 10×).
Malignant fibrous histiocytoma of larynx with giant cell: case report and histological-clinical considerations
Figure 7 – IHC stain for CD68 in large and giant
tumoral cells (ob. 10×).
Figure 8 – Variable stain for S100 in spindle-shaped
cells (ob. 10×).
Figure 9 – Smooth muscle actin (SMA) positive in
medium size vessels within the tumor mass (ob. 10×).
Figure 10 – SMA focally positive in spindle cells
Figure 11 – CD34 positive in numerous vessels and
negative in tumor cells (ob. 4×).
Figure 12 – EGFR-positive in blood vessels and
negative in tumor cells (IHC, ob. 10×).
Figure 13 – IHC stain for Ki67 in about 30–40% of
tumor cells nuclei (ob. 10×).
Fl. Anghelina et al.
Kauffman SL and Stout AP introduced the term
MFH in 1961 in order to describe a histiocytic-like
tumor with predominant fibroblasts .
Approximately 3 to 10% of all MFHs are localized
in the head and neck and the most common localizations
are in the naso-sinusal cavities (30%), the cranio-facial
bones (15–25%) and in the larynx (10–15%) [4, 7, 8].
Less than 50 cases (laryngeal MFH) have been
published in medical literature [9, 10].
MFHS are histologically divided into five types:
pleomorphic, myxoid, inflammatory, giant cells and
Giant cell rich malignant fibrous histiocytoma
accounts for 3–15% of all malignant fibrous
histiocytomas . This case is the first report of
laryngeal giant cell malignant fibrous histiocytoma in
medical literature (MEDLINE, PubMed search).
Laryngeal MFH is more commonly found at men
patients rather than in women patients . It appears
mostly in middle-aged or older adults .
Frequently, the primary localization of laryngeal
MFH at men is the glottis, whereas at women it is the
subglottis [4, 7, 13].
Dysphonia is the most common primary symptom;
dysphagia and dyspnea can also be observed, depending
on the size and the localization of the lesion . In our
case, severe dyspnea with dysphonia, stridor and
tiredness are due to large size of tumor and they were
necessitated emergency tracheotomy.
A direct laryngoscopy and tumor biopsy or
excision were essential for establishing a correct
In laryngoscopy, the most common presentation is
that of epithelial nodules or polyps . The great
dimension is due to patient negligence.
The final diagnosis is based on showing that
the tumor cells are histiocytes and that this is derived
from the mononuclear phagocytic system – essential to
distinguish it from other fibroblast like tumors .
Pathologically, MFH is composed of a mixture of
spindle-shaped fibroblastic tumor cells and bizarre
mononuclear histiocytic tumor cells arranged in whorl
pattern beneath the epithelium, and some multinucleated
giant cells. A pathological diagnosis, especially in head
and neck tumors, is difficult .
The neoplasic cells were diffused positive for
vimentin and histiocytic marker CD68, and focally
positive in spindle cells for neuroectodermic marker
(S100) and smooth muscle actin (SMA). In other
authors’ work, S100 and SMA were negative .
In our case, MFH had myofibroblastic features with
immunoreactivity for SMA.
Differential diagnosis includes: pleomorphic rhabdo-
myosarcoma, fibrosarcoma, spinocellular carcinoma,
angiosarcoma, hemangiopericytoma, pleomorphic lipo-
sarcoma and lymphoma .
Surgery with block resection of tumor is the first
choice of treatment for the majority of authors and
surgical technique varies, depending on the size and
localization of the tumor [12, 16–20].
Radiotherapy and chemotherapy does not have any
further advantages in comparison with surgical
treatment . Radiotherapy is used at patients with high
risks, at recurrence of non-operated patients and in cases
of metastasis to distance .
MFH of the larynx determines local and distance
metastasis, especially to brain and lungs [4, 12, 16, 17,
The prognosis depends on tumor differentiation,
vascular invasion, size and on the existence or not of
metastasis . Approximately 60% of the patients may
survive more than 5 years, and 40% of the patients may
survive more than 10 years .
Malignant fibrous histiocytomas with giant cell of
larynx are very rare mesenchymal neoplasm (this case
seems the first reported). The diagnosis of MFH of
larynx was difficult and the immunohistochemistry
could have been helpful.
 RESTA L., PENNELLA A., FIORE M. G., BOTTICELLA M. A.,
Malignant fibrous histiocytoma of the larynx after
radiotherapy for squamous cell carcinoma, Eur Arch
Otorhinolaryngol, 2000, 257(5):260–262.
histiocytoma: an analysis of 200 cases, Cancer, 1978,
 KAUFFMAN S. L., STOUT A. P., Histiocytic tumors (fibromas,
xanthoma and histiocytoma) in children, Cancer, 1961,
 BARNES L., KANBOUR A., Malignant fibrous histiocytoma of
the head and neck. A report of 12 cases, Arch Otolaryngol
Head Neck Surg, 1988, 114(10):1149–1156.
 POCH BROTO J., POCH VIÑALS R., FERNÁNDEZ S. M., SANZ J.,
MATA P., Histiocitoma fibroso maligno de la base del
cráneo, Acta Otorrinolaringol Esp, 1987, 38(5):329.
 ORTIZ BISH F., RUIZ CLEMENTE J., GALERA RUIZ H.,
DE MINGO FERNÁNDEZ E. J., MUÑOZ BORGE F., Malignant
laryngeal fibrous histiocytoma (MLFH). Report of two
unusual cases, Acta Otorrinolaringol
 BARNES L., FERLITO A., Soft tissue neoplasms. In:
FERLITO A. (ed), Neoplasms of the larynx, Churchill
Livingstone, Edinburgh, 1993, 265–304.
 LISNER CONTRERAS I., RAMOS MACIAS A., DÍAZ M., CASTRO-
LÓPEZ TARRADUELLE V., MEDINA ORTEGA C., Fibrohistio-
citoma maligno de laringe, An Otorrinolaringol Ibero Am,
 KUWABARA H., SAITO K., SHIBANUSHI T., KAWAHARA T.,
Malignant fibrous histiocytoma of the larynx, Arch Otorhino-
laryngol, 1994, 251(3):178–182.
 SALEEM M., MCARTHUR P. D., HAINAU B., VELAGAPUDI S. B.,
Fibrous histiocytoma of the larynx, J Laryngol Otol, 1998,
 RAO S., ARCOT R., PAI V., PRATHIBA D., Disseminated
malignant fibrous histiocytoma (giant cell rich): a case
report, Indian J Pathol Microbiol, 2007, 50(4):795–797.
 GODOY J., JACOBS J. R., CRISSMAN J., Malignant fibrous
histiocytoma of the larynx, J Surg Oncol, 1986, 31(1):62–65.
 BLITZER A., LAWSON W., BILLER H. F., Malignant fibrous
histiocytoma of the head and neck, Laryngoscope, 1977,
87(9 Pt 1):1479–1499.
 NAKAMIZO M., YOKOSHIMA K., SUGISAKI Y., Malignant fibrous
histiocytoma of the hypopharynx: a case report in a young
adult, J Nippon Med Sch, 2004, 71(4):301–305.
 BERNALDEZ R., NISTAL M., KAISER C., GAVILÁN J., Malignant
fibrous histiocytoma of the larynx, J Laryngol Otol, 1991,
F. M., Malignant fibrous
Malignant fibrous histiocytoma of larynx with giant cell: case report and histological-clinical considerations Download full-text
 CANALIS R. F., GREEN M., KONARD H. R., HIROSE F. M.,
fibrosarcoma) of the larynx, Arch Otolaryngol, 1975,
 KEENAN J. P., SNYDER G. G., TOOMEY J. M., Malignant
fibrous histiocytoma of the larynx, Otolaryngol Head Neck
Surg, 1979, 87(5):599–603.
 MAJUMDER N. K., SHARMA H. S., SRINIVASAN V., Malignant
fibrous histiocytoma of larynx. J Laryngol Otol, 1989,
 RAMADASS T., BALASUBRAMANIAM V. C., ANNAMALAI L.,
Malignant pleomorphic fibrous histiocytoma of the larynx.
A case report with review of literature, J Laryngol Otol,
Florin Anghelina, Assistant Professor, MD, PhD candidate, ENT Department, University of Medicine and
Pharmacy of Craiova, 2–4 Petru Rareş Street, 200349 Craiova, Romania; Phone +40742–031 003, e-mail:
Received: April 1st, 2009
fibrous xanthoma (xantho-
 BARBOSA F. H., DE OLIVEIRA RANGEL M., COELHO S. R.,
PATROCÍNIO J. A., PATROCÍNIO L. G., Malignant fibrous
histiocytoma of the larynx, Intl Arch Otorhinolaryngol,
São Paulo, 2006, 10(3):242–244.
 FERLITO A., NICOLAI P., RECHER G., NAME S., Primary
laryngeal malignant fibrous histiocytoma: review of the
literature and report of seven cases, Laryngoscope, 1983,
Accepted: June 10th, 2009