A Rare Case of A Low-Grade Inflammatory Leiomyosarcoma/Histiocyte-Rich Rhabdomyoblastic Tumor in the Neck of An Adolescent Male
Bharat REKHI1,2, Munita BAL1,2, Bhaskar DHARAVATH2,3, Amit DUTT2,3 , Prathamesh PAI4
1Department of Pathology Tata Memorial Hospital, MUMBAI, INDIA
2Homi Bhabha National Institute (HBNI) University, MUMBAI, INDIA
3Integrated Genomics Laboratory, Advanced Centre for Treatment, Research and Education In Cancer, Tata Memorial Centre, NAVI MUMBAI , INDIA
4Department of Surgical Oncology (Head and Neck Disease Management Group), Tata Memorial Hospital, HBNI University, MUMBAI, INDIA
Keywords: Soft tissue neoplasms, Neck, Leiomyosarcoma, Rhabdomyosarcoma, Histiocytes
Inflammatory leiomyosarcoma (LMS) is a newly included rare tumor entity in the group of smooth muscle tumors in the recent WHO
classification. Recent studies have shown skeletal muscle expression within this tumor and its proximity with histiocyte-rich rhabdomyoblastic
A 17-year-old male presented with a soft tissue lump over the back of his neck of one-year duration. Radiologically, a lesion measuring 5.9 cm in the
largest dimension was seen, extending from the skull base up to the C2 vertebral level, abutting the occipital bone. The initial biopsy was reported
as a fibrohistiocytic tumor at the referring laboratory. A microscopic review of the sections from the initial biopsy and subsequent resection
revealed a well-circumscribed, cellular tumor composed of plump spindle and polygonal-shaped tumor cells with relatively bland nuclei, moderate
to abundant eosinophilic cytoplasm and numerous interspersed histiocytes, including foam cells and lymphocytes. Immunohistochemically, the
tumor cells were positive for desmin, MYOD1 and SMA, focally positive for myogenin, while negative for h-caldesmon, SOX10 and S100P. A
diagnosis of inflammatory leiomyosarcoma/HRRT was offered. Subsequently, the tumor was tested for MYOD1 (L122R) mutation and was
found to be negative. The patient underwent adjuvant radiation therapy and is free-of-disease at 12 months post-treatment.
This case constitutes an extremely rare case of an inflammatory LMS/HRRT, identified in the neck region. This tumor should be differentiated
from its close mimics, such as a spindle cell/sclerosing rhabdomyosarcoma, as the latter is treated more aggressively, including with chemotherapy,
given its relatively poor prognosis.
An inflammatory leiomyosarcoma (LMS) is an extremely
uncommon malignant mesenchymal tumor, presently
included within the tumors of smooth muscle lineage 1
This is mostly reported in adult males, in sites such as the
deep soft tissues of the lower limb, trunk, proximal limbs
and in the retroperitoneum, followed by rare sites such as
lung, ovary and parapharyngeal region, the latter sites in
the form of isolated cases 1-5
Histopathologically, inflammatory LMS is characterized
by myogenic differentiation, accompanied by a prominent
inflammatory component and genetically displays nearhaploidization
1-2. Recent studies have shown a variable
amount of rhabdomyoblastic differentiation within this
tumor 3,5-7. Recently, Cloutier et al. 7 have shown
“kinship” between an inflammatory LMS and a histiocyterich
rhabdomyoblastic tumor (HRRT).
To the best of our knowledge, only two cases of HRRT have
been reported in the neck region of adult males 7.
A 17-year-old male presented with complaints of a soft
tissue lump over the back of his neck of one-year duration,
which seemed to be increasing in size over the last 6 months.
On clinical examination, a firm, immobile lump over the
right side of his neck behind the mastoid area was noted,
measuring 5 cm x 4 cm. In addition, a healed horizontal
scar of the previous open biopsy was noted. There was no
neurological deficit. There was no other lesion elsewhere in
his body (Figure 1).
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|Figure 1: Clinical photograph showing a lump in the right side of
neck behind the mastoid region, along with a healed horizontal
scar of the previous biopsy.
Computed tomography (CT) scan revealed a well-defined,
hypodense lesion in the intermuscular plane over the
postero-inferior and lateral aspect of the occipital region,
extending up to the right mastoid region. On magnetic
resonance imaging (MRI), there was a lesion measuring
5.3 cm x 5.9 cm x 5.0 cm, extending from the skull base
superiorly up to the C2 vertebral level, abutting the
occipital bone, leading to its thinning. Medially, the lesion
was seen extending into the interlaminar space and neural foramina of C1-C2 vertebra, and above the C1 lamina. It
is seen abutting the thecal sac. The lesion abutted the V3
or extraspinal segment of the right vertebral artery (~ 180
degrees). Anteriorly, it was seen extending up to the carotid
space. There was no intracranial extension and/or spinal
cord compression (Figure 2A).
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|Figure 2: A) MRI revealing a lesion
measuring 5.9 cm in the largest
dimension, extending from the
skull base superiorly up to the
C2 vertebral level, abutting the
occipital bone. B) Cut surface of
the resected tumor showing a wellcircumscribed
border with a grey-
A B white homogenous surface.
An incisional biopsy, performed and then reported as
a fibrohistiocytic neoplasm at the referring laboratory,
was reviewed at our Institution. Thereafter, the patient
underwent an excision.
An unoriented specimen measuring 7.5 cm x 6.5 cm x
5 cm was received. On serial sectioning, a tumor was
identified measuring 7.5 cm in the largest dimension. The
cut surface was homogeneous, whitish in appearance and
firm in consistency. There were no areas of necrosis and
hemorrhage (Figure 2B).
Tissue sections revealed a well-circumscribed cellular
tumor, with a thin pseudocapsule, composed of plump,
spindle-shaped and polygonal or epithelioid cells, arranged
in fascicles and bundles, and occasionally separated by a
variable amount of hyaline and focally myxoid stroma. The
individual tumor cells displayed oval to elongated nuclei,
distinct nucleoli and moderate to abundant amount of
eosinophilic to amphophilic cytoplasm with tapering ends.
There was lack of significant nuclear atypia, mitotic figures,
tumor necrosis and cells with cross striations on extensive
tissue sampling. In addition, several histiocytes, including
foamy cells and lymphocytes were interspersed throughout
the tumor, obscuring the tumor cells in certain areas. Focal
areas of tumor cells infiltrating the skeletal muscles were
noted (Figures 3A,B, 4A-D).
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|Figure 3: Microscopic findings (Biopsy).
A) Cellular tumor composed of intersecting
fascicles of spindle cells with intervening
inflammatory cells. (H&E, x 200). B) Higher
magnification showing plump spindle cells with
tapering eosinophilic cytoplasm and scattered
lymphocytes and histiocytes. (H&E, x 400).
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|Figure 4: Microscopic findings (resected specimen). A) A circumscribed tumor with a well-defined pseudocapsule. (H&E, x 100).
B) A cellular tumor displaying cells with spindle and polygonal shapes, and interspersed histiocytes and lymphocytes. (H&E, x 400).
C) Foamy histiocytes and lymphocytes admixed with spindle-shaped tumor cells. (H&E, x 400). D) Tumor cells containing moderate to
abundant cytoplasm with tapering ends, vesicular nuclei, exhibiting minimal nuclear atypia and interspersed histiocytes. (H&E, x 400).
Immunohistochemically, the tumor cells were positive for
desmin (monoclonal, D33), MYOD1 (multifocal staining)
(monoclonal, 5.8A); focally expressed smooth muscle actin
(SMA) (monoclonal, 1A4) and myogenin (monoclonal,
L026), while negative for S100 protein, SOX10, heavy
isoform of caldesmon (H caldesmon) (monoclonal, h-CD)
and ALK (monoclonal, D5F3). SMARCB1/INI1 expression was retained. Additionally, CD68 and CD163 highlighted
numerous interspersed histiocytes (Figure 5A-D, 6A-B).
A diagnosis of an inflammatory LMS/HRRM was offered
on the biopsy and further confirmed on the resection.
In addition, the tumor was tested for MYOD1 (L122R)
mutation by polymerase chain reaction (PCR), using
forward and backward primers 8, followed by Sanger
sequencing and was proved to be negative for MYOD1
(L122R) mutation (Figure 7).
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|Figure 5: Immunohistochemical results. A) Tumor cells displaying desmin positivity. Diaminobenzidine, x 400. B) Multifocal MYOD1
positivity. (DAB, x 400). C) SMA positivity. DAB, x 400. D) CD163 highlighting several interspersed histiocytes and few tumor cells.
(DAB, x 400).
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|Figure 6: Immunohistochemical results.
Focal myogenin positivity. (DAB, x 200).
B) Low Ki67/MIB1. (DAB, x 400).
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|Figure 7: Sanger sequencing chromatogram of MYOD1 shown
with reference sequence. No mutation found with forward and
reverse sequencing reads. Arrow indicates nucleotide position.
The tumor was focally abutting the cauterized surface.
Therefore, the patient was offered adjuvant radiation
therapy. He has been free of disease for the last 12 months.
Inflammatory LMS is a recently included neoplasm in the
category of smooth muscle tumors in the current WHO
classification of tumors of the soft tissues. At the same time,
this tumor entity has created an interesting discussion, regarding its terminology, in view of its histogenesis and its
clinical behavior. In two different studies, the authors have
challenged its smooth muscle lineage and proposed alternate
terminologies, such as “low-grade myofibroblastic tumor”
and more recently, “inflammatory rhabdomyoblastic
tumor”, including proximity between an inflammatory
LMS and a histiocyte-rich rhabdomyoblastic tumor
(HRRT), given that these tumors exhibit striking skeletal
muscle differentiation 5,6
. The present case constitutes
the first case of an inflammatory leiomyosarcoma/HRRT,
identified in the neck of an adolescent male, who was
initially diagnosed with a fibrohistiocytic tumor at the
referring laboratory. Previously, only two cases of HRRT
have been reported, in a 45-year-old male and 26-year-old
Histopathologically, the presence of plump spindled cells
in the present case led to various differential diagnoses,
such as an inflammatory myofibroblastic tumor (IMFT), malignant peripheral nerve sheath tumor (MPNST) and a
spindle cell/sclerosing rhabdomyosarcoma. Although there
were plump cells with an abundant eosinophilic cytoplasm
and tapering ends, resembling rhabdomyoblasts, there were
no cross striations identified. Immunohistochemically,
apart from desmin and focal SMA immunoreactivity, tumor
cells also displayed multifocal myoD1 and focal myogenin positivity. This ruled out an IMFT. Moreover, the tumor
cells were negative for ALK overexpression. Lack of S100P
and SOX10 positivity ruled out an MPNST. However,
spindle cell/sclerosing RMS was a close differential
diagnosis, given the location and distinct rhabdomyoblastic
differentiation. Despite rhabdomyoblastic differentiation,
the lack of significant nuclear atypia, mitotic figures and
a conspicuous amount of inflammatory component,
including histiocytes, throughout the tumor, raised the
possibility of spindle cell/ sclerosing RMS, although less
likely. The inflammatory component was composed of
mature lymphocytes and macrophages. In one of the
earlier series, the authors observed that the lymphocytes
were mostly CD3-positive T lymphocytes, along with
a small population of CD20-positive B lymphocytes.
Furthermore, Ki-67/MIB1 highlighted 1-2% of tumor cell
nuclei (low). Similarly, Michal et al. 5 observed low Ki67/
MIB1 in all five tumors in their study. Moreover, MYOD1
immunostaining revealed multifocal positivity in the
present case, in contrast to diffuse staining that is reported
in most spindle cell/sclerosing rhabdomyosarcomas 8-12. Presence of an admixture of plump spindle cells and
inflammatory cells had led to an erroneous diagnosis of
granulomatous inflammation on FNAC at the referring
laboratory. Much earlier, these tumors were misdiagnosed
as inflammatory malignant fibrous histiocytomas 1. The
other morphological features described in an inflammatory
LMS are Touton type of giant cells and focal psammomatous
Furthermore, we tested the present case for the MYOD1
(LI22R) mutation that constitutes a characteristic mutation
underlying most cases of spindle cell/sclerosing RMS 8,12.
The absence of MYOD1 (L122R) mutation was additionally
useful in ruling out a spindle cell RMS, as similarly reported
in five cases of HRRT, earlier by Martinez et al. 6.
During the initial description of an inflammatory LMS,
Merchant et al. 1 observed a consistent immunoreactivity
in the tumor cells for desmin, and variable immunopositivity
for SMA and HHF-35. Chang et al. 4 reported negative
immunoexpression for myogenin in all of their three study
cases. Subsequently, using global gene expression profiling,
Arbajian et al. 3 demonstrated a conspicuous differential
expression of genes involved in muscle differentiation and
function, including those of skeletal muscle differentiation,
namely ITGA7, MYF5, MYF6, MYO1, MYOG and PAX7
in an inflammatory LMS. Thereafter, Michal et al. 5
reported positive immunostaining for MYOD1, myogenin
and PAX7 in nine cases of inflammatory LMS. In view
of co-expression of smooth and skeletal muscle specific
markers, they proposed a reclassification of this tumor as
a low-grade inflammatory myogenic tumor. Cloutier et
al. 7 demonstrated proximity between an inflammatory
LMS and histiocyte-rich rhabdomyoblastic tumor
(HRRT), in the form of co-expression of desmin, SMA,
MYOD1 and myogenin in four cases of inflammatory
LMS and nine cases of HRRT and proposed reclassifying
these tumors as inflammatory rhabdomyoblastic
tumors. Apart from desmin, myogenin and MYOD1
positivity, none of the tumors in their study was positively
immunoreactive for h caldesmon, which is considered
as the most specific immunohistochemical marker of
smooth muscle differentiation, as similarly noted in the
present case 4,6-7,13. Chang et al. 4 suggested that
inflammatory leiomyosarcomas might lack smooth muscle
differentiation. On the other hand, Arbajian et al. 3 and
Michal et al. 5, reported h-caldesmon positivity in 3/4
cases and 5/8 cases of inflammatory LMS, in two different
studies, respectively. However, there was a difference in
the clone of h-Caldesmon in those studies 3,5. Similar to
the study by Cloutier et al. 7, we tested the current tumor
with the h-CD clone of h-caldesmon, rather than E89.
Apart from the positive immunoexpression of skeletal
muscle specific markers, these tumors display significant
number of CD68 and or CD163 positive histiocytes that
seem to obscure the tumor cells, as well as expressed by
some tumor cells, as observed in the present case and also
in the previously reported cases. 1,3,5-7. It would be
worth exploring whether the inflammatory component,
including lymphocytes and macrophages are reactive or tumor-associated cells. This might have a possible bearing
on the outcome of these tumors.
The importance of identifying this rare tumor is in view
of its relatively favorable prognosis, unlike a spindle cell/
sclerosing RMS that invariably shows an aggressive clinical
course, in adult patients, especially those displaying the
MYOD1 (L122R) mutation 3-7,8,12. Post-excision and
adjuvant radiation therapy, the present case has been free of
disease for a year. None of the five cases harboring tumors
in the somatic soft tissues in the study by Michal et al. 5
developed recurrences or metastasis. Similarly, none of the
nine previously reported cases in three different studies
developed tumor recurrences or metastasis over a period of
5-120 months 3,6-7.
Regarding its genetic profiling, Dal Cin et al. 14 reported
near-haploid genotype in two cases of inflammatory LMS.
Subsequently, various authors demonstrated similar results
in various cases of inflammatory LMS 3,4,7,15. Despite
most chromosomes showing loss of heterozygosity,
heterozygosity for chromosomes 5 and 22 and frequently
for 18, 20 and 21 chromosomes has been reported to be
retained in this tumor 3 4,6,14,15. Moreover, oncogenic
inactivating mutations in the NF1 gene have been reported
in few cases of inflammatory LMS and HRRTs 5,6. In
addition, Martinez et al. 6 reported a likely benign PTCH1
polymorphism (rs115556836:c.2183C>T:pThr728Met) in a
single case of HRRT. Unfortunately, genetic profiling was
not performed in the recent case.
In conclusion, the present case constitutes a rare case of
an inflammatory leiomyosarcoma/HRRT, identified in
the neck of an adolescent male. Given the diagnosis of an
inflammatory LMS, the patient was spared of intensive
chemotherapy that is invariably offered to most cases of
RMS, especially large-sized tumors. Although extremely
rare, this entity should be included in the differential
diagnosis of a spindle cell tumor showing co-expression
of smooth and skeletal muscle markers, with a prominent
histiocytic component and rare mitoses. An exact diagnosis
of this tumor with an evolving terminology has significant
Conflict of Interest
We declare that we have no conflict of interest.
Concept, design, data collection, analysis/interpretation, literature
search, writing and approval: BR, Data collection, analysis, writing
and approval: MB, Interpretation, writing and approval: BD,
Interpretation writing and approval: AD, Data collection, writing and
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