Diagnostic challenges with intraoral myeloid sarcoma: report of two cases & review of world literature
Background: Myeloid sarcomas (MS) are rare extramedullary tumors composed of blasts of myeloid lineage that either precede, follow or present concomitantly with acute myeloid leukaemia (AML) or myeloproliferative neoplasms. The diagnosis of MS is especially challenging in patients without an anteced...
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
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| Цитувати: | Diagnostic challenges with intraoral myeloid sarcoma: report of two cases & review of world literature / P. Kumar, H. Singh, N. Khurana, A.B. Urs, J. Augustine, R. Tomar // Experimental Oncology. — 2017 — Т. 39, № 1. — С. 78-85. — Бібліогр.: 64 назв. — англ. |
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irk-123456789-1376012018-06-22T15:46:05Z Diagnostic challenges with intraoral myeloid sarcoma: report of two cases & review of world literature Case report Background: Myeloid sarcomas (MS) are rare extramedullary tumors composed of blasts of myeloid lineage that either precede, follow or present concomitantly with acute myeloid leukaemia (AML) or myeloproliferative neoplasms. The diagnosis of MS is especially challenging in patients without an antecedent history of leukemia. Methods: We present 2 cases of intraoral MS that presented as de novo lesions. A detailed review of cases of intraoral MS that either preceded or presented along with leukemia has been done with emphasis on diagnostic criteria used. Results: Two male patients aged 28 and 5 years presented with MS with one patient presenting with concomitant AML. A combination of morphological and immunohistochemical methods was used for diagnosis. A thorough review of world literature revealed 44 cases of intraoral MS that presented as de novo lesions. Conclusion: Intraoral MS is a rare tumor with poor prognosis. It may be diagnostically challenging due to its protean clinical manifestations and histological overlap with other tumors. 2017 Article Diagnostic challenges with intraoral myeloid sarcoma: report of two cases & review of world literature / P. Kumar, H. Singh, N. Khurana, A.B. Urs, J. Augustine, R. Tomar // Experimental Oncology. — 2017 — Т. 39, № 1. — С. 78-85. — Бібліогр.: 64 назв. — англ. 1812-9269 http://dspace.nbuv.gov.ua/handle/123456789/137601 en Experimental Oncology Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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Case report Case report |
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Case report Case report Diagnostic challenges with intraoral myeloid sarcoma: report of two cases & review of world literature Experimental Oncology |
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Background: Myeloid sarcomas (MS) are rare extramedullary tumors composed of blasts of myeloid lineage that either precede, follow or present concomitantly with acute myeloid leukaemia (AML) or myeloproliferative neoplasms. The diagnosis of MS is especially challenging in patients without an antecedent history of leukemia. Methods: We present 2 cases of intraoral MS that presented as de novo lesions. A detailed review of cases of intraoral MS that either preceded or presented along with leukemia has been done with emphasis on diagnostic criteria used. Results: Two male patients aged 28 and 5 years presented with MS with one patient presenting with concomitant AML. A combination of morphological and immunohistochemical methods was used for diagnosis. A thorough review of world literature revealed 44 cases of intraoral MS that presented as de novo lesions. Conclusion: Intraoral MS is a rare tumor with poor prognosis. It may be diagnostically challenging due to its protean clinical manifestations and histological overlap with other tumors. |
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Article |
| title |
Diagnostic challenges with intraoral myeloid sarcoma: report of two cases & review of world literature |
| title_short |
Diagnostic challenges with intraoral myeloid sarcoma: report of two cases & review of world literature |
| title_full |
Diagnostic challenges with intraoral myeloid sarcoma: report of two cases & review of world literature |
| title_fullStr |
Diagnostic challenges with intraoral myeloid sarcoma: report of two cases & review of world literature |
| title_full_unstemmed |
Diagnostic challenges with intraoral myeloid sarcoma: report of two cases & review of world literature |
| title_sort |
diagnostic challenges with intraoral myeloid sarcoma: report of two cases & review of world literature |
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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2017 |
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Case report |
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http://dspace.nbuv.gov.ua/handle/123456789/137601 |
| citation_txt |
Diagnostic challenges with intraoral myeloid sarcoma: report of two cases & review of world literature / P. Kumar, H. Singh, N. Khurana, A.B. Urs, J. Augustine, R. Tomar // Experimental Oncology. — 2017 — Т. 39, № 1. — С. 78-85. — Бібліогр.: 64 назв. — англ. |
| series |
Experimental Oncology |
| first_indexed |
2025-07-10T04:05:57Z |
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2025-07-10T04:05:57Z |
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1837231366119358464 |
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78 Experimental Oncology 39, 78–85, 2017 (March)
DIAGNOSTIC CHALLENGES WITH INTRAORAL MYELOID
SARCOMA: REPORT OF TWO CASES & REVIEW OF WORLD
LITERATURE
P. Kumar1, *, H. Singh1, N. Khurana2, A.B. Urs1, J. Augustine1, R. Tomar2
1Department of Oral Pathology, Maulana Azad Institute of Dental Sciences, BSZ Marg, New Delhi 110002, India
2Department of Pathology, Maulana Azad Medical College, BSZ Marg, New Delhi 110002, India
Background: Myeloid sarcomas (MS) are rare extramedullary tumors composed of blasts of myeloid lineage that either precede, fol-
low or present concomitantly with acute myeloid leukaemia (AML) or myeloproliferative neoplasms. The diagnosis of MS is espe-
cially challenging in patients without an antecedent history of leukemia. Methods: We present 2 cases of intraoral MS that presented
as de novo lesions. A detailed review of cases of intraoral MS that either preceded or presented along with leukemia has been done with
emphasis on diagnostic criteria used. Results: Two male patients aged 28 and 5 years presented with MS with one patient presenting
with concomitant AML. A combination of morphological and immunohistochemical methods was used for diagnosis. A thorough review
of world literature revealed 44 cases of intraoral MS that presented as de novo lesions. Conclusion: Intraoral MS is a rare tumor with
poor prognosis. It may be diagnostically challenging due to its protean clinical manifestations and histological overlap with other tumors.
Key Words: myeloid sarcoma, leukemia, granulocytes, immunohistochemical method.
Myeloid sarcoma (MS) is a pathologic diagnosis for
an extramedullary proliferation of blasts of one or more
myeloid lineages that leads to effacement of the tissue
architecture in which it is found [1]. Originally called
chloromas due to the greenish color on gross exami-
nation attributed to production of myeloperoxidase,
it has subsequently undergone numerous changes
in nomenclature including granulocytic tumor, extra-
medullary myeloid tumor and myeloblastoma. This
change in nomenclature reflects the various facets
of the historical evolution of this tumor corresponding
with molecular and cytogenetic understanding of the
neoplasm.
MS is usually observed in a setting of acute myeloid
leukemia (AML), myeloproliferative neoplasms and
mixed myelodysplastic/myeloproliferative neoplasms
(50%). Appearance of MS in an AML patient in remis-
sion is an indication of relapse. Rarely MS has pre-
sented after allogenic stem cell transplantation [2, 3].
15–35% of MS cases are detected concomitantly with
AML, however, it is the remaining 25–27% that precede
AML that create a diagnostic dilemma.
Intraoral MS is an exceedingly rare lesion with only
about 75 cases reported since its first description
in 1811. Almost all intraoral sites can be involved includ-
ing the jaws, gingiva, hard and soft plate, tonsils, maxil-
lary sinus, tongue and lips. Here we present two cases
of intraoral MS along with review of world literature.
Emphasis has been placed on the diagnostic criteria
used by various authors. We also present differential
diagnosis, approaches to diagnosis and pitfalls in di-
agnosing MS when it precedes or is diagnosed with
AML based on review of world literature.
CASE REPORTS
Case I
A 28 year old monoplegic male presented with
a progressively enlarging swelling on left side of face,
since 5–6 months (Fig. 1, a). He had undergone ex-
traction of 36.2 months ago due to mobility. Physical
examination revealed ill defined bony hard swelling
extending from the left ala tragus line up to lower bor-
der of mandible with involvement of ramus and angle
of mandible. Intraorally, expansion on buccal aspect of
#34 to #37 and healed extraction socket of #36 were
noted. Orthopantomogram showed ill defined mixed
radiolucent and radiopaque lesion with respect to left
angle of mandible extending up to the ramus of man-
dible (Fig. 1, b). Laboratory studies including complete
blood count and serum chemistry were within normal
range.
Incisional biopsy was performed via intraoral
approach. Histopathological examination revealed
a diffuse infiltration of large atypical cells with vesicu-
lar nuclei with predominance of crushed nuclei. The
atypical cells were seen infiltrating in between and
splaying the muscle fibers (Fig. 1, c). A basic immu-
nohistochemical panel consisting of pancytokeratin,
vimentin, S100, CD45, and desmin was performed.
The tumor cells were positive for CD45 (Fig. 1, d)
and a presumptive diagnosis of non-Hodgkin’s lym-
phoma was made. However, the cells were negative
for CD3 and CD20. The H&E slides were re-examined
and a population of large cells containing eosinophilic
granules (Fig. 1, e) was seen intermingling with the
tumor cells with areas of degranulation.
Based on all previous investigations and histo-
pathological findings, anti-myeleoperoxidase antibody
(anti-MPO) staining (Fig. 1, f) was performed which
showed strong diffuse positivity. Bone marrow biopsy
was within normal limits. A diagnosis of MS in the ab-
sence of AML was thus made.
Submitted: November 18, 2016.
*Correspondence: E-mail: drpri_kumar@yahoo.com
Abbreviations used: AML — acute myeloid leukemia; MPO — mye-
leoperoxidase; MS — myeloid sarcoma.
Exp Oncol 2017
39, 1, 78–85
CASE REPORTS
Experimental Oncology 39, 78–85, 2017 (March) 79
Patient underwent induction chemotherapy with cy-
tarabine and idarubucin with lesion regression. He has
remained in remission for 14 months after diagnosis
with normal blood counts.
Case II
A 5 year old male child was referred to our Centre
by a private dentist with rapidly progressing mildly
tender swelling in left posterior mandibular region
(Fig. 2, a), since last 10 days. History of trauma was
elicited 25 days prior to commencement of swelling
and there was no history of any systemic disease.
Examination revealed a well defined bony hard swell-
ing with expansion of buccal and lingual cortices. The
left deciduous molars were mobile and displaced due
to the swelling (Fig. 2, b). A large area of ulceration
was noted on the linguo-occlusal aspect. Orthopan-
tomogram showed an ill defined mixed radiolucent
radiopaque lesion causing resorption of molar roots
ba
e
c
fd
Fig. 1. Clinical, radiographic, histological and immunohistochemical findings of Case #1: a — extra oral photograph showing dif-
fuse swelling over left mandible; b — orthopantogram showing poorly defined mixed radiolucent-radio opaque mottled lesion with
partially healed socket of #36; c — microphotograph showing tumor cells invading in between and splaying muscle fibers (H & E,
× 100); d — microphotograph showing diffuse positivity for CD45; e — higher magnification showing granular eosinophilic myelocytes
(arrow) intermingling with immature tumor cells (H & E, × 1000); f — microphotograph showing strong positivity for MPO
ba
f
c
d e g
Fig. 2. Clinical, radiographic and histological findings of Case #2: a — extra oral photograph showing swelling over left angle of mandible
that showed rapid expansion over a period of 1 week post incisional biopsy (f); b — intraorally, swelling with expansion of buccal and lingual
cortices and ulcer over the linguo-occlusal surface covered by grayish pseudomembrane was observed at first visit; c — orthopantogram
showing ill defined radiolucent lesion involving left posterior mandible causing resorption of molar roots (note the sunburst pattern at the
periphery); d — microphotograph with pleomorphic round to spindled tumor cells (H & E, × 100); e — microphotograph showing immature
tumor cells with varying degree of pleomorphism and mitotic activity (H & E, × 1000); f — 1 week post biopsy, a massive increase in swell-
ing; g — 1 week post biopsy, the lesion showing massive expansion with an irregular, granular and necrotic appearance
80 Experimental Oncology 39, 78–85, 2017 (March)
and a periosteal reaction giving a sunburst appear-
ance (Fig. 2, c). Other than decreased hemoglobin
level of 10.5 gm/dl, all other hematological parameters
were within normal limits.
An incisional biopsy was subsequently performed
along with extraction of the mobile teeth. Biopsy
showed diffuse infiltration of predominantly round cells
effacing the tissue architecture. The cells had sparse
to moderate eosinophilic cytoplasm with prominent
nuclei. Abundant mitotic figures were seen with mito-
ses ranging from 5–6 per high power field (Fig. 2, d, e).
Based on H & E sections, Ewing’s sarcoma, em-
bryonic rhabdomyosarcoma, and neuroblastoma were
included in the differential diagnosis. The tumor cells
were negative for vimentin, desmin, CD99, CD45 and
NSE. In the mean time, the patient reported with
a massive increase in swelling (7 days post biopsy)
(Fig. 2, f, g).
A peripheral smear was repeated and numerous
immature blasts including myeloblasts, and band
forms were observed (Fig. 3, a). Immunohistoche-
mistry was then done using anti-MPO (Fig. 3, b) and
anti-CD34 (Fig. 3, c). The tumor cells were diffusely
positive for MPO and focally positive for CD34. The
lesion was thus diagnosed as MS. Subsequently, bone
marrow biopsy was performed that showed marrow
involvement with atypical cells with high nuclear-to-
cytoplasmic ratio, focal nuclear convolutions and
moderate to scant cytoplasm (Fig. 3, d). These atypical
cells constituted more than 50% of marrow population.
Strong MPO activity was also noticed in these atypical
cells. MS presenting with AML was the final diagno-
sis. The left deciduous second molar was decalcified
and showed dense diffuse infiltration by tumor cells
completely obliterating the pulpal architecture (Fig. 4).
Patient underwent chemotherapy with cytarabine
followed by successful lesion regression. He is cur-
rently in remission, one year post diagnosis.
A thorough search of world literature revealed
77 cases of intraoral MS, of which 44 lesions either
preceded or presented concomitantly with leukemia.
Diagnostic criteria used for these lesions (MS present-
ing with or preceding leukemia) have been compiled
in Table 1 [1–46].
DISCUSSION
The diagnosis of MS can be a clinical challenge
when there is no antecedent myeloid neoplasm. It has
been reported that up to 27% cases present de novo
and there may be a lag of up to 10 months between
first presentation and bone marrow involvement [45,
46]. A high degree of clinical suspicion thus becomes
mandatory in order to establish diagnosis. In a study
of 26 MS cases by Menasce et al. [47], 14 were initially
misdiagnosed, all 14 being without prior history of leu-
kemia or myeloproliferative disorders. Further Byrd
et al. [48] in their study found that up to 46% of pub-
lished isolated cases were misdiagnosed, commonly
as large cell lymphomas. The differential diagnosis
of MS is quite large and clinical features such as age
b
a
d
c
Fig. 3. Cytological and immunohistochemical findings
of Case #2: a — peripheral smear showing presence of band
forms and myeloblasts (Giemsa, × 100); b — diffuse positivity
for MPO seen in all tumor cells (× 100); c — focal positivity for
CD34 observed in some tumor cells (× 100), d — bone marrow
aspirate showing numerous blast cells (Giemsa, × 100)
Experimental Oncology 39, 78–85, 2017 (March) 81
along with presence of a preexisting or concurrent
myeloid neoplasm must be factored in.
The pathogenesis of MS has been attributed
to an aberrant homing signal for the leukemic blast
cells rather than their localization within the bone
marrow [1]. Studies have shown that this homing and
retention of the blasts may be mediated by different
chemokine/chemokine receptor activations and the
invasive potential of the cells is due to interactions
between MMPs and integrins [49–51].
The clinical features of oral MS can be extremely
variable and nonspecific. Patients may present with
swelling, sore throat, purulent discharge, jaw pain,
mobile teeth, sinus pain, tonsillar enlargement and
lymphadenopathy amongst others [41]. MS has
been reported at almost all intraoral sites with the
mandible accounting for the maximum number
of cases (35%). The most common site for extraoral
MS is the skin (leukemia cutis) where it presents
as multiple papules, plaques and nodules [34].
Radiographically, intraosseous oral lesions vary
from innocuous appearing periapical granulomas/
abscesses and superficial bony erosion to massive
destructive expansile lesions involving large areas
of the jaw [1, 9, 11, 52]. Periosteal reactions around
the lesion and sinus haziness are some of the other
reported findings.
Morphologically, MS classically presents as a tu-
mor composed of immature cells namely myeloblasts,
monoblasts and rarely promyelocytes that partially
or completely efface the overall architecture of the
tissue involved. The cells show scant cytoplasm with
multilobed round to oval nuclei, fine or dusty nuclear
chromatin and one or two small basophilic nucleoli [53,
54]. MS were historically divided into granulocytic
sarcoma and monocytic sarcoma. Pileri et al. [45]
in 2007 further classified GS into three variants
as per the morphological type. Blastic variant shows
predominance of myeloblasts with little evidence
of maturation and no cytoplasmic granules, immature
type (intermediate grade) consists of myeloblasts,
promyelocytes and eosinophilic myelocytes and dif-
ferentiated or mature type shows promyelocytes, and
more mature cells with abundance of eosinophils.
According to this classification, Case #1 belongs
to the differentiated type and Case #2 to the blastic
type. However, the cytomorphologic classification
has no bearing on prognosis and is hence clinically
irrelevant [47, 55].
With increase in cytogenetic and molecular under-
standing of these tumors, the abovementioned mor-
phological distinctions seem less relevant. At the same
time, sufficient knowledge regarding the immunohis-
tochemical makeup of the various subtypes may prove
critical in establishing diagnosis. A number of studies
describing the immunophenotype of MS have shown that
the tumor can show features of any myeloid lineage and
often may show multiple lineage expression in the same
tumor [34, 53]. A number of enzyme cytochemical stains
such as myeloperoxidase, sudan black B, chloracetate
ba
d
c
Fig. 4. Decalcified section of left permanent first molar (Case #2) showing diffuse infiltration and effacement of pulpal architecture
by tumor cells: a — H&E, × 20; b — H&E, × 40; c — H&E, × 40; d — H&E, × 400
82 Experimental Oncology 39, 78–85, 2017 (March)
Table 1. Diagnostic criteria used for intraoral MS preceding or presenting with leukemia
No. Authors/Reference Year Age/
Sex Location Type of ma-
lignancy Diagnosis based on:
Marrow sta-
tus at the
time of di-
agnosis
Time to leukaemia
diagnosis
1 Wiernick et al. [4] 1970 35/F Cheek AML H & E Uninvolved 10 months after MS
2 Brooks et al. [5] 1974 8/M Maxillary sinus AML H & E Uninvolved 4 years
3 Hansen et al. [6] 1982 83/F Maxilla AML NA Uninvolved 3 months after MS
4 Conran et al. [7] 1982 2/F Mandible None H & E
Ultrastructural analysis
Uninvolved DF
5 Takagi et al. [8] 1983 25/F Mandible AML IHC — MPO Uninvolved 1 year 6 mos after MS
6 Reichart et al. [9] 1984 35/F Mandible AML, pro-
myelocytic
CS — chloracetate esterase Uninvolved 3 months after MS
7 Castella et al. [10] 1984 89/F Hard palate None CS — chloracetate esterase
Ultrastuctural analysis
DF Died of unrelated
cause
8 Timmis et al. [11] 1986 52/M Mandible LL CS — Sudan black, chloracetate esterase
IHC — HLA, Leu-M3
Ultrastructural analysis
Involved Diagnosed with MS
9 Ficarra et al. [12] 1987 67/F Hard palate AML CS — chloracetate esterase 1 year 3 mos after MS
10 De Vicente
Rodriquez et al. [13]
1990 56/M Left mandible AML CS — chloracetate esterase
IHC — lysozyme
Involved Diagnosed with MS
11 Eisenberg et al.
[14]
1991 33/M Multiple sites None CS — Sudan black, MPO, α-naphthyl buty rate
esterase
Uninvolved DF
12 Stack et al. [15] 1994 70/M Mandible CML CS — chloroacetate esterase; IHC — antilyso-
zomal peroxidase
Involved Diagnosed with MS
13 Roth et al. [16] 1995 47/M Gingiva AML NA NA NA
14 Lynch et al. [17] 1998 86 /F Maxillary gingiva AML IHC — MPO Uninvolved 2 years 5 mos after MS
15 Tong et al. [18 ] 2000 76 /F Maxillary gingiva AML IHC — MPO Uninvolved 7 months
16 Amin et al. [19] 2002 58/M Hard palate AML IHC — CD34 (weak)
FC — HLA-DR, CD11c, CD13, CD15, CD34, TdT
CG – trisomy 13 (47,XY,+13)
Involved Diagnosed with MS
17 Jordan et al. [20] 2002 62/F Mandible AML CS — chloracetate esterase
IHC — CD43, MPO, CD15
CG — normal
Uninvolved 6 weeks
18 Antmen et al. [21] 2003 12/F Gingiva AML IHC — MPO, lysozyme Uninvolved Few weeks after MS
19 Stoopler et al. [22] 2004 50/M Multiple sites AML IHC — LCA, CD43, CD34 (rare) Involved Diagnosed with MS
20 Colella et al. [23] 2005 62/F Maxillary gingiva AML IHC — MPO, lysozyme, CD45, CD68 Uninvolved Few weeks after MS
21 Koudstaal
et al. [24]
2006 36/M Hard palate AML IHC — CD45, CD43, HLA-DR, CD4 (weak)
FC — CD117, CD56, CD13, HLA-DR, CD45,
CD33 (weak)
CG — abnormal
Uninvolved 2 years
22 Goteri et al. [25] 2006 84/F Hard palate None IHC — CD45, CD43, CD34, MPO, CD68 Uninvolved DF
23 Yinjun et al. [26] 2006 44/F Gingiva None IHC — MPO, CD68
CG — trisomy 21
Uninvolved DF
24 Yoon et al. [27] 2006 63/M Gingiva AML IHC — CD117, MPO Involved Diagnosed with MS
25 Matsushita
et al. [28]
2007 50/M Maxillary gingiva AML IHC — MPO, CD43 Involved Diagnosed with MS
26 Mohmedbhai
et al. [29]
2008 45/M Tongue AML IHC — CD45, MPO, CD68
FC — MPO, CD33, CD117
CG — t(15;17) (q22;q12)
Involved Diagnosed with MS
27 Kim et al. [30] 2009 4 /F Mandible AML IHC — MPO, CD34, CD43, CD79a,
FC — CD13, CD33, CD38, CD117, HLA-DR, MPO
Involved Diagnosed with MS
28 Lu et al. [31] 2009 63/F Maxillary gingiva AML IHC — MPO, CD34, CD3 (rare), CD20 (rare) Involved Diagnosed with MS
29 Lu et al. [31] 2009 39/F Maxilla None IHC — MPO, CD34 Uninvolved DF
30 Papamanthos
et al. [32]
2010 70/F Mandible AML IHC — CD43, lysozyme, MPO Involved Diagnosed with MS
31 Qiu et al. [33] 2010 16/F Condyle AML NR Involved Diagnosed with MS
32 Klco et al. [34] 2011 39/M Maxillary gingiva AML IHC — MPO, CD117, CD4, CD34 Uninvolved DF
33 Colović et al. [35] 2011 55/F Mandible None (HIV) IHC — CD117, CD45, CD68, lysozyme,
CD13 (weak)
Uninvolved Dead at 8 months
(HIV related sepsis)
34 Seema et al. [36] 2011 5/M Mandible AML IHC — MPO, TdT Involved Diagnosed with MS
35 Mei et al. [37] 2011 56/M Multiple None IHC — CD34, CD45, CD56, CD117, MPO Uninvolved DF
36 Yamashita et al.
[38]
2012 1/M Mandible AML IHC — CD45
FC — CD33, CD65, MPO
Involved Diagnosed with MS
37 Kurdoğlu et al. [39] 2013 29/F Gingiva AML IHC — CD117, MPO NR NR
38 Guastafierro
et al. [40]
2013 56/F Maxillary gingiva None (pleu-
ral effusion)
IHC — CD45, CD68, lysozyme, MPO Uninvolved Died due to other
causes
39 Zhou et al. [41] 2013 77/F Tongue MDS CS — chloracetate esterase
IHC — CD4, CD1c, CD33, CD43, CD68, CD117,
CD163, MPO, lysozyme
CG — 47,XX,+8[20]
Involved Diagnosed with MS
40 Zhou et al. [41] 2013 55/M Mandible CML IHC — MPO, CD43
CG — 46,XY,t(9;22) (q34;q11) [20]
Involved Diagnosed with MS
41 Zhou et al. [41] 2013 47/F Tonsil AML IHC — CD4, CD11c, CD33, CD43, CD45, CD68,
CD117, MPO, lysozyme, CD163
CG — normal
Involved Diagnosed with MS
42 Sharma et al. [42] 2014 9/M Maxillary sinus DF IHC — CD31, MPO, vimentin, CD99 Uninvolved DF
43 Ponnam et al. [43] 2014 45/F Mandible NA IHC — CD45, CD68, CD117, MPO NR NR
44 Moshref et al. [44] 2014 45/M Multiple sites DF (MI) IHC — CD45, C-Kit Uninvolved Died due to MI after
10 months
Experimental Oncology 39, 78–85, 2017 (March) 83
esterase, α-naphthyl acetate esterase and α-naphthyl
butyrate esterase have also been described.
Although the immunohistochemical panel for
MS is well established, diagnosis may still be difficult
for tumors presenting in the absence of a known
primary. CD43 and lysozyme having a high sensiti-
vity but low specificity are the most commonly used
markers. Other routinely used markers include MPO,
CD68 (KP-1 clone), CD34, CD45, CD117 and CD33.
However, tumors of purely monocytic origin are nega-
tive for CD34, CD117 and MPO and positive for CD68,
CD43, and CD33 [34, 53, 56].
A guide to the immunohistochemical differential
diagnosis of MS is given in Table 2.
The most common differential diagnosis for MS in the
adult population is non-Hodgkin’s lymphoma (T & B cell
type) [47]. It is especially true for T cell neoplasms
as MS may express many markers of T cell differentiation
namely, CD2, CD4, CD7, CD43, and CD45. Immature
MS with no evidence of differentiation is usually mis-
diagnosed as diffuse large B cell lymphoma which has
thick nuclear membrane and basophilic nucleoli, unlike
myeloblasts or monoblasts, which have thin nuclear
membranes and pinpoint nucleoli [57]. The use of a com-
prehensive immunohistochemical panel including lyso-
zyme, MPO and CD68 thus becomes mandatory when
dealing with such lesions. Other neoplasms that need
to be differentiated are poorly differentiated carcinomas,
melanomas and epitheloid sarcomas.
In pediatric population, differentiating MS from
small round blue cell tumors such as Ewing’s, primitive
neuroectodermal tumors, neuroblastoma and alveolar
rhabdomyosarcoma may become challenging. As seen
in the case reported here, the radiographic appear-
ance of a destructive radiolucent lesion surrounded
by periosteal reaction giving a sun burst appearance
may also favor a diagnosis of Ewing’s sarcoma. The
expression of CD99 by a large number of nonmono-
cytic MS further impedes diagnosis. However, positive
expression of CD43, lysozyme and MPO swings the
diagnosis in favor of MS. While dealing with children
and young adults, it is prudent to exclude Langerhans
cell histiocytosis from the differential diagnosis. The
grooved coffee bean like nuclei of Langerhan’s cells
and abundance of eosinophils in the background
is often seen in the monocytic MS [58].
Apart from immunohistochemistry, flow cytomet-
ric analysis using CD13, CD33, CD117 and MPO for
non-monoblastic MS and CD14, CD163, and CD11c
in monoblastic MS is well established when fresh tis-
sue is available [1]. Cytogenetic abnormalities have
been reported in approximately 50% of the MS cases
and mirror the cytogenetic changes associated with
AML. Interestingly, de novo cases of MS may lack
these abnormalities. Pileri et al. [45] through FISH
demonstrated trisomy 8 and monosomy 7 as the most
common abnormalities. Trisomy 8 and inv (16) as de-
termined by conventional cytogenetics was reported
by Alexeiv et al. [59]. Pediatric patients having t(8;21)
(q22;22) karyotypic abnormality have been shown
to have a predilection for head and neck involvement
including the orbit and CNS [60].
Molecular abnormalities in MS are not very well
established. Mutations in nucleophosmin (NPM) 1 and
No. Authors/Reference Year Age/
Sex Location Type of ma-
lignancy Diagnosis based on:
Marrow sta-
tus at the
time of di-
agnosis
Time to leukaemia
diagnosis
45 Present case 2016 28/M Left mandible DF IHC — CD45, MPO Uninvolved DF
46 Present case 2016 5/M Left mandible AML IHC — MPO, CD34 Involved Diagnosed with MS
Notes: CG — cytogenetics; CML — chronic myeloid leukemia; CS — cytochemical staining; DF — disease free; F — female; FC — flow cytometry; HIV — human
immudeficiency virus; HLA — human leukocyte antigens; IHC — immunohistochemistry; LL — lymphoblastic lymphoma; M — male; MDS — myelodysplastic
syndrome; MI — myocardial infarction; NA — not available; NR — not reported.
Table 2. Immunohistochemical differential diagnosis of MS
Antibody Specificity
MS Non-Hodg-
kin’s lymphoma
Ewing
sarco-
ma
Epithe-
loid sar-
coma
Poorly dif-
ferentiated
carcinoma
Melano-
ma
Lan gerhans
cell histio-
cytosis
Nonmono-
cytic
Mono-
cytic B cell T cell
CD43 T cells, myeloid cells, subset of B cells, T & B cell lymphomas +++ +++ ++ +++ − − − − −
Lysozyme Myeloid & monocyte/macrophage lineage cells +++ +++ − − − − − − −
MPO Myeloid lineage cells +++ − − − − − − − −
CD68 Monocyte/macrophage lineage cells ++ ++ − − − − − − −
CD34 Vascular progenitor cells, endothelial cells, interstitial
cells of cajal, leukemic blasts, some soft tissue tumors
++ − − − − ++ − − −
CD45 T & B lymphocytes, monocytes, macrophages, mast
cells & weakly on granulocytes
+ + +++ +++ − − − − −
CD117 Interstitial cells of cajal, germ cells, bone marrow stem
cells, breast epithelium, melanocytes & mast cells
++ − − − − − − − −
CD33 Cells of myeloid lineage, some lymphoid cells ++ + − − − − − − −
CD3 T lymphocytes + − − +++ − − − − −
CD20 B lymphocytes − − +++ − − − − − −
CD99 Ewing sarcoma, primitive neuroectodermal tumor,
periphe ral neuroepithelioma
+ − + ++ +++ − − − −
Others CD79a FLI1
S100
NSE
CK
INI-1
Vimentin
EMA
High & low
weight CK
HMB 45
Melan A
S 100
CD1a
S100
Note: +++ strongly positive, ++ frequently positive, + rarely positive, — negative.
84 Experimental Oncology 39, 78–85, 2017 (March)
its resultant aberrant cytoplamic expression have been
reported in approximately 15% of MS patients [61]. The
prevalence of Fms like tyrosine kinase-3 (FLT3) muta-
tions has been reported in a small subset of MS ca-
ses [62]. The significance of these mutations on the
prognosis of MS patients is yet unknown.
With respect to available therapeutic options, there
is a lack of consensus on treatment of MS with the
recommended treatment regimen being conventional
AML type chemotherapeutic protocols [1]. The role
of radiotherapy in addition to chemotherapy is not well
established with many studies showing no additional
benefit [63, 64]. Other therapeutic modalities include
hematopoietic stem cell transplantation and targeted
therapy [1]. The prognosis of patients with MS is usu-
ally poor with slightly better outcomes when compared
to primary or relapsed AML without extramedullary
involvement. MS accompanying chronic myeloid leuke-
mia or myelodysplastic syndrome is said to have a worse
clinical outcome when compared to MS with AML.
To conclude, intraoral MS is a rare tumor with poor
clinical outcome. It has protean clinical manifestations
and histological overlap with numerous tumors making
it a diagnostic challenge for clinicians and pathologists
alike. When evaluating a tumor of unknown etiology,
it is wise to maintain a high degree of suspicion espe-
cially if common antibody panels are negative for epi-
thelial, mesenchymal or lymphoid markers. Apart from
immunohistochemistry, use of ancillary techniques
such as cytogenetics and bone marrow examination
may assist in diagnosing. Arriving at prompt accurate
diagnosis facilitates timely and effective therapeutic
intervention thus improving patient outcomes.
Conflict of interest: Nil.
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