Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_100_библиотеки_им_акад_М_И_Перельмана
.pdf
Lymphoid and Myeloid Tumors, Pathology of the Ovary 159
https://t.me/med1917
Cheson, B. D., Fisher, R. I., Barrington, S. F., et al. (2014).
Recommendations for initial evaluation, staging, and
response assessment of Hodgkin and non-Hodgkin
lymphoma: The Lugano classification. Journal of Clin-
ical Oncology, 32 , 3059–3068.
Cho, H. Y., Kim, Y. B., No, J. H., Kim, K., & Paik, J. H.
(2011). Primary extranodal marginal zone B-cell lymphoma of MALT-type involving the fallopian tube.
Gynecologic Oncology Case Reports.
Cho HY, Kim YB, No JH, Kim K, Paik JH. Primary
extranodal marginal zone B-cell lymphoma of MALTtype involving the fallopian tube. Gynecol Oncol Case
Rep. 2011 Oct 30;2(1):6–8. https://doi.org/10.1016/j.
gynor.2011.10.005. PMID: 24371599; PMCID:
PMC3861282.
Gaffan, J., Herbertson, R., Davis, P., Dogan, A., & Jones,
A. (2004). Bilateral peripheral T-cell lymphoma of
the fallopian tube. Gynecologic Oncology, 95,
736–738.
Garcia, M. G., Deavers, M. T., Knoblock, R. J., Chen, W.,
Tsimberidou, A. M., Manning, J. T., Jr., & Medeiros,
L. J. (2006). Myeloid sarcoma involving the gynecologic tract: A report of 11 cases and review of the
literature.). American Journal of Clinical Pathology,
125, 783–790.
Hernández, J. A., Navarro, J. T., Rozman, M., Ribera,
J. M., Rovira, M., Bosch, M. A., Fantova, M. J.,
Mate, J. L., & Millá, F. (2002). Primary myeloid sarcoma of the gynecologic tract: A report of two cases
progressing to acute myeloid leukemia. Leukemia &
Lymphoma, 43, 2151–2153.
Magdy, M., Abdel Karim, N., Eldessouki, I., Gaber, O.,
Rahouma, M., & Ghareeb, M. (2019). Myeloid sarcoma. Oncology Research and Treatment, 42,
224–229.
Nezhat, C. H., Dun, E. C., Wieser, F., & Zapata, M. (2013).
A rare case of primary extranodal marginal zone B-cell
lymphoma of the ovary, fallopian tube, and appendix in
the setting of endometriosis. American Journal of
Obstetrics and Gynecology, 208(1), e12–e14.
Noack, F., Lange, K., Lehmann, V., Caselitz, J., & Merz,
H. (2002). Primary extranodal marginal zone B-cell
lymphoma of the fallopian tube. Gynecologic Oncol-
ogy, 86(3), 384–386.
Oliva, E., Ferry, J. A., Young, R. H., Prat, J., Srigley, J. R.,
& Scully, R. E. (1997). Granulocytic sarcoma of the
female genital tract: A clinicopathologic study of
11 cases. The American Journal of Surgical Pathology,
21, 1156–1165.
Scully, R. E., Young, R. H., & Clement, P. B. (1998).
Tumors of the ovary, maldeveloped gonads, fallopian
tube and broad ligament (AFIP atlas of tumor pathol-
ogy series 3; fascicle 23). Washington, DC: Armed
Forces Institute of Pathology.
Tripathi, R., Sharma, B., Chaturvedi, K. U., Khurana, N.,
& Mala, Y. M. (2005). Granulocytic sarcoma of the
female genital tract: Report of a case with an unusual
presentation. Gynecologic and Obstetric Investigation,
59, 189–191.
Lymphoid and Myeloid
Tumors, Pathology of the
Ovary
Feras Zaiem
Detroit Medical Center/Wayne State Uni versity,
Detroit, MI, USA
Ovarian Hematolymphoid Lesions
Description
The ovaries are the most common female reproductive organs to have lymphoma (Kurman et al.
2011). However, primary ovarian lymphomas are
rare and account for fewer than 1% of overall
lymphoma (Dimopoulos et al. 1997). It occurs in
girls and women with an age range from 18 months
to 74 years and a peak incidence in the fourth and
fifth decades (Dimopoulos et al. 1997).
Few ovarian lymphoma cases have reported
uncommon association with serous borderline
tumor (Skodras et al. 1994) and exceedingly rare
with teratoma (McKelv ey et al. 2003). The clinical presentation is not specific and includes
abdominal or pelvic pain, abdominal distension,
or lymphoma B symptoms such as fever, night
sweats, or weight loss (Dimopoulos et al. 1997).
Almost all ovarian lymphomas in adolescents
and children are aggressive high-grade B-cell
lymphoma including diffuse large B-cell lymphoma and Burkitt’s lymphoma (Kosari et al.
2005). On the other hand, adults may have indo-
lent or aggressive lymphoma. Ovarian lymphoma
is an aggressive tumor with extraovarian spread or
advanced stage in most of the cases (Dimopoulos
et al. 1997). However, the prognosis is recently
considered similar to the counterpart lymph node
lymphoma of comparable grade and stage
(Dimopoulos et al. 1997).
Diffuse Large B-Cell Lymphoma
Definition
Diffuse large B-cell lymphoma (DLBCL) is an
aggressive lymphoma, composed of medium to
L
160 Lymphoid and Myeloid Tumors, Pathology of the Ovary
https://t.me/med1917
large B lymphoid cells. It usually arises de novo
(primary) or can represent a transformation
of a less aggressive non-Hodgkin lymphoma
(secondary).
Clinical Features
DLBCL is the most common primary ovarian
lymphoma (Nasioudis et al. 2017; Dimopoulos
et al. 1997).Itismorecommonlyseeninelderly
individuals with a peak incidence in the seventh
decade of life (Swerdlow et al. 2017).
It is an aggressive but curable tumor. The
standard treatment of advanced-stage DLBCL
is R-CHOP regimen - rituximab, cyclo phosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate (Oncovin),
and prednisone-. The 5-year overall survival
and progression-free rates are 56% and 60%,
respectively (Swerdlow et al. 2017).
Microscopy
The histologic examination shows sheets growth
patterns composed of neoplastic medium to large
B-lymphocytes with three morphological variants
(Fig. 1). Centroblastic variant is the most common
one and the lymphocytes are oval to round with
scant amphophilic to basophilic cytoplasm, vesicular chromatin and two to four nucleoli.
Immunoblastic variant where >90% of the cells
are immunoblasts with basophilic cytoplasm and
one nucleolus. Anaplastic variant is the rarest and
characterized by large cells with bizarre pleomorphic nuclei, that might have cohesive growth pattern and may be confused with undifferentiated
carcinoma (Swerdlow et al. 2017).
Immunophenotype
Tumor cells express B cell markers (CD19, CD20,
CD22, CD79a and PAX5) and surface and cytoplasmic immunoglobulin (mostly commonly
Lymphoid and Myeloid Tumors, Pathology of the
Ovary, Fig. 1 Primary ovarian diffuse large B-cell lym-
phoma. a–b. Sheets of diffuse lymphoid infiltrates composed of discohesive intermediate to large atypical
lymphocytes. c. CD20 immunostaine highlighting the
tumor cells. d. Ki67 proliferation index demonstrates
80–90% activity
Lymphoid and Myeloid Tumors, Pathology of the Ovary 161
https://t.me/med1917
IgM) in 50–75% of the cases. The neoplastic cells
express MYC and BCL2 markers, and it is considered positive if >40% and >50% of the tumor
cells stain positive, respectively. Cases that are
positive for MYC marker along with BCL2
and/or BCL6 are designated as “double
expresser” and “triple expresser.”
The Hans algorithm using three markers is
widely used to distinguish the germinal center
B-cell (GCB) type from activated B-cell type
(ABC). Those three markers are CD10, BCL6
and IRF4/MUM1. Each is considered positive if
>30% of the tumor cells are positive. The GCB
immunophenotype is CD10+, BCL6+/,
MUM1+/ or CD10, BCL6+, MUM1. The
ABC immunophenotype is all other combination.
The neoplastic cells have high Ki67 proliferation
index usually >40% and reach >90% in some
cases (Swerdlow et al. 2017).
Molecular Features
The most common translocation in ovarian
DLBCL is BCL6 mutation in 30% of the cases
and it is seen more in ABC subtypes. BCL6 translocation is associated with improved survival.
Translocation of BCL2 gene i.e. t(14;18)(q32;
q21.3) is observed 20–30% and it occurs more
frequently in GCB subtype. The presence of
BCL2 is associated with inferior survival in GCB
DLBCL patients treated with R-CHOP. MYC
rearrangement occurs in 8–14% of the cases. It is
evenly distributed between the GCB and ABC
subtypes and has been associated with inferior
survival.
About half of the DLBCL that harbor MYC
translocation also show a BCL2 and/or BCL6
translocation. The latter belong to the new category of high-grade B-cell lymphoma, so called
“double-hit” if it has MYC and BCL2 or BCL6
rearrangement and “triple-hit lymphoma” if it harbors the three mutations (Swerdlow et al. 2017).
Follicular Lymphoma
Definition
Follicular lymphoma (FL) is a neoplasm composed of follicle center B-cells which usually has
at least partially a follicular pattern.
Clinical Features
The ovaries - along the vulva and vagina - are the
most common female gential organ to have FL
(Nasioudis et al. 2017). It mostly affects older
patients with highest incid ence in the United
States and Western Europe. The prognosis of FL
is closely related to the extent of the disease at
diagnosis and cytologic grade. FL is generally
very responsive to radiation and chemotherapy
(Swerdlow et al. 2017).
Microscopy
The microscopic examination of follicular lymphoma is compa rable to that in nodal and extranodal sites and shows follicular proliferation
patterns with closely packed follicles (Lagoo and
Robboy 2006; Vang et al. 2001). Neoplastic follicles may be irregular and serpiginous and have
attenuated or absent mantle zones. The neoplastic
follicles are composed of centroblasts,
centroblasts with almost absent tingible body
macrophages. Centrocytes are small to medium
cells with scant cytoplasm, cleaved nuclei and
inconspicuous nucleoli. Centroblasts are large
cells with round to oval nuclei, vesicular chromatin and one to three peripheral nucleoli. The number of centroblasts is the basis of FL grading
system. Grade 1–2 (low grade) defined as presence of less than 15 centroblasts per high power
field. Grade 3 (high grade) when there are more
than 15 centroblasts per high power field
(Swerdlow et al. 2017).
Immunophenotype
Tumor cells express B-cell markers (CD19,
CD20, CD22, and CD79a). BCL2 marker is the
hallmark of FL and help to distinguish neoplastic
from reactive follicles, although absence of BCL2
does not entirely exclude the diagnosis of
FL. BCL2 protein is expressed in 85–90% of
grade 1–2 FL and in less than 50% of grade
3 FL. FL is usually positive for BCL6, and variably CD10. The Ki67 proliferation index usually
correlates with the grade, where grade 1–2 have
Ki67 < 20% and grade 3 have a proliferation
index >20%.
Follicular dendritic cell (FDC) markers including CD21 and CD23 highlight the follicular pattern. A diffuse area is defined as an area that lacks
L
162 Lymphoid and Myeloid Tumors, Pathology of the Ovary
https://t.me/med1917
follicles pattern as evident by the absence of
CD21/CD23 FDC markers. This helps define the
three FL patterns as follicular (>75% follicular),
follicular and diffuse (25–75% follicular) and diffuse (<25% follicular). However, the presence of
diffuse areas of predominantly large centroblasts
is equivalent to DLBCL (Swerdlow et al. 2017).
Molecular Features
The FL has a characteristic t(14;18)(q32;q21)
translocation between IGH and BCL2 genes.
However, it is typically seen in secondary ovarian
follicular lymphoma, whereas primary cases often
lack this translocation (Naresh et al. 2011). The t
(14;18) translocation is present in around 90% of
grade 1–2 and in less frequency of grade 3 cases.
The absence of this translocation has no impact on
prognosis. Fluorescence in situ hybridization
(FISH) is more sensitive than polymerase chain
reaction (PCR) for detecting this translocation due
to variation in breakpoint regions. Also, 5–15% of
FL cases harber BCL6 rearrangement (Swerdlow
et al. 2017).
Burkitt’s Lymphoma
Definition
Burkitt’s lymphoma is an aggressive B-cell lymphoma characterized by high proliferation activity
and usually, MYC translocation.
Clinical Features
Burkitt’s lymphoma (BL) has three variants; sporadic, endemic and immunodeficiency-related.
Sporadic BL is seen mainly in children and
young adults worldwide with EBV genome in
20–30% of the cases. Endemic BL occurs mostly
in African children with an average age of 4 to7
years (Mbulaiteye et al. 2012) with more than
95% of the cases harbor EBV mutation.
Immunodeficiency-associated BL is mostly seen
in the setting of HIV infection (Raphael et al.
1991) with 25–40% of EBV positive cases.
BL uniquely tends to involve both ovaries
(Lagoo and Robboy 2006). BL is a highly aggressive neoplasm but potentially curable tumor.
Intensive chemotherapy has a 70–90% overall
survival with girls doing better than adults
(Swerdlow et al. 2017).
Microscopy
Microscopic examination shows diffuse proliferation of medium-sized monotonous atypical lymphocytes. The tumor cells have basophilic
cytoplasm, round nice and fine clumped chromatin. The tumor has high mitotic figures and apoptotic bodies. Scattered tingible body
macrophages are also evident and account for
the classic starry sky ap pearance on low pattern.
Burkitt’s lymphoma in the setting of immunodeficiency may show plasmacytoid differentiation
with slightly more cytoplasmic and eccentric
nuclei (Leoncini et al. 2008).
Immunophenotype
The neoplastic cells express B-cell antigens
(CD19, CD20, CD22, CD79a and PAX5) and
moderate to strong membrane immunoglobulin
IgM with light chain restriction. They have strong
expression of MYC protein and also express
germinal-centre markers CD10 and BCL6
(Swerdlow et al. 2017). The Ki-67 proliferation
index is high, almost 100%. The tumor cells are
negative for BCL2, CD5 and CD23 (Naresh et al.
2011). The endemic variant of Burkitt’s lym-
phoma has a characteristic Epstein-Barr virus
(EBV) positivity (Leoncini et al. 2008).
Molecular Features
The molecular hallmark of BL is the translocation
of MYC gene resulting in t(14:18) (q24;q32).
However, MYC translocation is not specificto
BL and can be seen in other types of lymphoma.
Around 10% of BL cases lack the MYC
rearrangement (Swerdlow et al. 2017).
Myeloid Sarcoma
Definition
Myeloid sarcoma is an extramedullary tumor
mass consisting of primitive myeloid elements
(Brunning et al. 2001) that is rarely seen in the
ovary (Oliva et al. 1997). Myeloid sarcoma may
occur de novo, may precede or coincide with
Lymphoid and Myeloid Tumors, Pathology of the Ovary 163
https://t.me/med1917
acute myeloid leukemia (AML), or it could be
the initial manifestation of relapse in a patient
with previously diagnosed AML (Kashofer
et al. 2018).
Clinical Features
Ovarian myeloid sarcoma shows complete remission and long-term survival in (Ga rcia et al. 2006).
However, clinical behavior and therapy response
is independent of age, site of involvement or type
of presentation.
Macroscopy
The ovary is often enlarged and has a fish-flesh
and a characteristic green surface when the neoplastic cells express myeloperoxidase, hence the
old name of myeloid sarcoma; “chloroma.”
Microscopy
Myeloid sarcoma most commonly consists of
myoblasts, with myelomonocytic or monoblastic
morphology in many cases. Rare cases with erythroid precursors or megakaryoblasts have been
reported (Swerdlow et al. 2017). The histologic
examination shows diffuse infiltration of monotonous medium-sized cells with fine chromatin and
small nucleoli. Mitoses and scattered apoptotic
bodies are evident. Geographic necrosis is rare
(Garcia et al. 2006; Oliva et al. 1997).
Immunophenotype
Histochemical stains are of major help with
myeloperoxidase (MPO) and lysozyme being the
most sensitive and specific stains. MPO and
chloroacetate esterase (CAE) positivity favor
granulocytic differentiation, where monoblastic
differentiation is more evident by nonspecific
esterase (NSE). In immunohistochemistry, neoplastic cells with immature myeloid profile
express CD33, CD34, CD68 and CD117 (c-kit).
The monoblastic variant expresses CD68, CD163
and CD14 but lacks MPO and CD34. Erythroid
myeloid sarcoma cases are positive for
glycophorin A and C, haemoglobin and CD71.
Megakaryoblast cases express CD61 and LAT
(Swerdlow et al. 2017).
Flow cytometry on cell suspension for myeloid
sarcoma with myeloid differentiation is positive
for CD13, CD33, CD117 (c-kit) and MPO. It
shows positivity for CD14, CD163 and CD11c
in monoblastic tumors (Swerdlow et al. 2017).
Molecular Features
Chromosomal aberrations are detected in about
55% of myeloid sarcoma, most commonly monosomy 7, trisomy 8, KMT2A rearrangement and inv
(16). NPM1 mutation is seen in about 16% of the
cases that frequently have myelomonocytic or
monoblastic morphology (Swerdlow et al. 2017)
(Fig. 1).
References and Further Reading
Brunning, R., Matutes, E., Flandrin,G., et al. (2001). Acute
myeloid leukemia not otherwise categorised. In E. Jaffe
et al. (Eds.), Pathology and genetics: Tumours of
haematopoietic and lymphoid tissues (pp. 91–105).
Lyon: IARC Press.
Dimopoulos, M. A., Daliani, D., Pugh, W., et al. (1997).
Primary ovarian non-Hodgkin ’s lymphoma: Outcome
after treatment with combination chemotherapy. Gyne-
cologic Oncology, 64, 446–450.
Garcia, M. G., Deavers, M. T., Knoblock, R. J., et al.
(2006). Myeloid sarcoma involving the gynecologic
tract: A report of 11 cases and review of the literature.
American Journal of Clinical Pathology, 125(5),
783–790.
Kashofer, K., Gornicec, M., Lind, K., et al. (2018). Detec-
tion of prognostically relevant mutations and translocations in myeloid sarcoma by next generation
sequencing. Leukemia & Lymphoma, 59(2), 501–504.
Kosari, F., Daneshbod, Y., Parwaresch, R., et al. (2005).
Lymphomas of the female genital tract: A study of
186 cases and review of the literature. The American
Journal of Surgical Pathology, 29(11), 1512–1520.
Kurman, R. J., Ellenson, L. H., & Ronnett, B. M. (2011).
Blasustein’s pathology of the female Geintal tract
(6th ed.). Springer.
Lagoo, A. S., & Robboy, S. J. (2006). Lymphoma of the
female genital tract: Current status. International Jour-
nal of Gynecological Pathology, 25(1), 1–21.
Leoncini, L., Raphael, M., Stein, H., et al. (2008). Burkitt’s
lymphoma. In S. Swerdlow et al. (Eds.), WHO classi-
fication of tumours of haematopoietic and lymphoid
tissues (pp. 262–264). Lyon: IARC Press.
Mbulaiteye, S. M., Anderson, W. F., Ferlay, J., et al.
(2012). Pediatric, elderly, and emerging adult-onset
peaks in Burkitt’s lymphoma incidence diagnosed in
four continents, excluding Africa. American Journal of
Hematology, 87(6), 573–578.
McKelvey, A., McKenna, D., McManus, D., et al. (2003).
A case of lymphoma occurring in an ovarian teratoma.
Gynecologic Oncology, 90(2), 474–477.
L
164 Lymphoid and Myeloid Tumors, Pathology of the Uterine Corpus
https://t.me/med1917
Naresh, K. N., Ibrahim, H. A., Lazzi, S., et al. (2011).
Diagnosis of Burkitt lymphoma using an algorithmic
approach – applicable in both resource-poor and
resource-rich countries. British Journal of
Haematology, 154, 770–776.
Nasioudis, D., Kampaktsis, P. N., Frey, M., Witkin, S. S., &
Holcomb, K. (2017). Primary lymphoma of the female
genital tract: An analysis of 697 cases. Gynecol Oncol
[Internet]. Elsevier Inc, 145, 305–309.
Oliva, E., Ferry, J. A., Young, R. H., et al. (1997). Granu-
locytic sarcoma of the female genital tract.
A clinicopathologic study of 11 cases. The American
Journal of Surgical Pathology, 21, 1156–1165.
Raphael, M., Gentilhomme, O., Tulliez, M., Byron, P. A.,
& Diebold, J. (1991). Histopathologic features of high
grade non–Hodgkin’s lymphomas in acquired immunodeficiency syndrome. The French Study group of
Pathology for Human Immunodeficiency VirusAssociated Tumors. Archives of Pathology & Labora-
tory Medicine, 115,15–20.
Skodras, G., Fields, V., & Kragel, P. J. (1994). Ovarian
lymphoma and serous carcinoma of low malignant
potential arising in the same ovary. A case report with
literature review of 14 primary ovarian lymphomas.
Archives of Pathology & Laboratory Medicine, 118,
647–650.
Swerdlow, S. H., Campo, E., Harris, N. L., Jaffe, E. S.,
Pileri, S. A., Stein, H., & Thiele, J. (2017). WHO
classification of tumors of hematopoietic and lymphoid
tissues (revised 4th ed.). Lyon: IARC.
Vang, R., Medeiros, L., Warnke, R., et al. (2001). Ovarian
non-Hodgkin’s lymphoma: A clinicopathologic study
of eight primary cases. Modern Pathology, 14(11),
1093–1099.
Lymphoid and Myeloid
Tumors, Pathology of the
Uterine Corpus
Feras Zaiem
Detroit Medical Center/Wayne State Uni versity,
Detroit, MI, USA
Uterus Hematolymphoid Lesions
(General Entry)
common presentation is abnormal vaginal bleeding, and less commonly pelvic or abdominal pain
(Ferry & Young, 1997) and systemic symptoms
such as fever or weight loss (Dursun et al., 2005;
Ferry & Young, 1997). Uterine lymphomas have a
relatively good prognosis (Ferry & Young, 1997;
Vang et al., 2001) with the majority being Ann
Arbor stage I rather than stage II (Chan et al.,
2005). The disease free survival is reported
between 70% and 90% (Chan et al., 2005; Dursun
et al., 2005).
The differential diagnosis of uterine lymphoma
includes florid reactive lymphoid hyperplasia,
chronic inflammatory processes, spindle cell sarcoma, low grade endometrial stromal sarcoma,
and embryonal rhabdomyosarcoma. However,
the discohesive monotonous tumor cells proliferation and the CD45+, CD20+, and CD 10+/ (for
B-cell lymphoma) may help in distinguishing
lymphoma from non-lymphoid neoplasms.
Diffuse Large B-Cell Lymphoma
Definition
Diffuse large B-cell lymphoma (DLBCL) is the
most common type of non-Hodgkin lymphoma
(NHL) in the United States and worldwide
(Al-Katib et al., 2020). It occurs in two settings,
either as a primary tumor or secondary as a transformation of a less grade non-Hodgkin
lymphoma.
Clinical Features
Diffuse large B-cell lymphoma is the most common uterine lymphoma accounting for about 70%
of its primary lymphoma (Vang et al., 2001). It
mostly affects elderly women in their sixth and
seventh decade of life. With the appropriate chemotherapy regime, it has a 56% of 5-year overall
survival and 60% of progression-free rates
(Swerdlow et al., 2017).
Description
Uterine lymphoma is rare and accounts for less
than 1% of all extranodal lymphoma (Freeman
et al., 1972). It affects females with an average
age of 50 years old (Dursun et al., 2005). The most
Microscopy
Microscopic examination shows diffuse growth
pattern of medium to large cells with three distinct
morphology varia nts: centroblasts, immunoblasts,
or anaplastic. Centroblastic variants is
Lymphoid and Myeloid Tumors, Pathology of the Uterine Corpus 165
https://t.me/med1917
characterized by lymphocytes with pale or
basophylic cytoplasm with two to three nucleoli.
Immunoblastic variant is characterized by majority of neoplastic cells with amphophilic cytoplasm, eccentric nuclei, and one central nucleoli.
Anaplastic variant has multilobated large anaplastic cells that may mimic undifferentiated epithelial
tumor (Swerdlow et al., 2017).
Immunophenotype
The neoplastic lymphocytes express pan B-cell
markers (CD19, CD20, CD22, CD79a, and
PAX5). The neoplastic cells also express MYC
and BCL2 variability. The cutoff of positivity for
MYC and BCL2 is >40% and > 50% of the
tumor cells stain positive, respectively. Double
expressor lymphoma is designated when the
DLBCL stain positive for MYC and BCL2 or
BCL6. Triple expressor lymphoma when there is
expression for all MYC, BCL2, and BCL6
(Swerdlow et al., 2017).
DLBCL has two distinctive subtypes; germinal
center B-cell (GCB) type and activated B-cell type
(ABC). Hasn algorithm using CD10, BCL6, and
IRF4/MUM1 helps in distinguishing the two subtypes. The cutoff to be positive for Hans three
markers is >30% of the tumor cells stain positive.
The GCB immunophenotype is (CD 10 +/,
BCL6+, MUM1-), where the ABC subtype
immunophenotype is (CD10-, BCL6+, MUM1+)
(Cao et al., 2017). The Ki67 proliferation index is
usually high of more than 50% and EVB is typically absent (Sun et al., 2015).
Molecular Features
The three most common DLBCL gene
rearrangements are BCL6, BCL2, and MYC
accounting for 30%, 20–30%, and 8–14% of the
cases. BCL6 translocation is seen more in ABC
subtype, BCL2 mutation is seen more in GBC
subtype, where MYC rearrangement is seen
almost equally in the two subtypes. Double-hit
lymphoma defined as DLBCL with the presence
of MYC translocation with BCL2 or BCL6, while
triple-hit lymphoma defined as the presence of the
three rearrangements. Both double-hit and triplehit lymphoma are under the category of high grade
B-cell lymphoma (Swerdlow et al., 2017).
Follicular Lymphoma
Definition
Follicular lymphoma (FL) is a slow-gr owing,
indolent form of non-Hodgkin lymphoma that
arises from B lymphocytes.
Clinical Features
Follicular lymphoma is the second most common
type of uterine lymphoma. It is more commonly
seen in the elderly population. The prognosis of
FL depends on the cytologic grade and clinical
stage. FL has a good prognosis with the appropriate chemotherapy (Swerdlow et al., 2017).
Microscopy
Microscopic examination shows back to back
lymphoid follicles proliferation. Those follicles
lack the polarity, mantle zones, tingible body macrophages. The follicles are composed of a mixture
of centrocyte (small cells with scant cytoplasm
and cleaved nuclei) and centroblasts (large cells
with vesicular chromatin and one to three peripheral nucleoli). The proportion of those two cell
types are used for lymphoma grading into three
tiers. Grade 1-2 (low grade) when there is <15
centroblasts per high power field and grade
3 (high grade) > 15 centroblasts per high power
field (Swerdlow et al., 2017). Follicular lym-
phoma of all three grads have been reported in
the uterus (Kosari et al., 2005).
Immunophenotype
The neoplastic cells express B-cell markers including CD19, CD20, CD22, and CD79a. BCL2 is the
hallmark marker and it is expressed in 85–90% of
grade 1-2 FL and in less than 50% of grade 3 FL.
However, absence of BCL2 does not exclude the
diagnosis of FL. BCL6 and CD10 are also
expressed in 60 to 70% of the cases. CD5 and
CD43 are negative. The Ki67 proliferation index is
usually <20% in grade 1-2 and > 20% in grade 3.
CD21 and CD23 are follicular dendritic cell
markers and highlight the follicular pattern.
Based on their expression, three patterns of FL
have been identifi ed: follicular (>75% follicular),
follicular and diffuse (25–75% follicular), and
diffuse (<25% follicular). However, the presence
L
166 Lymphoid and Myeloid Tumors, Pathology of the Uterine Corpus
https://t.me/med1917
of diffuse areas of predominantly large
centroblasts should be reported as diffuse large
B-cell lymphoma (Swerdlow et al., 2017).
Molecular Features
FL is characterized by the t(14;18)(q32;q21)
translocation between the IGH and BCL2 genes.
The t(14;18) translocation is seen in the majority
(90%) of grade 1-2 FL and in much less frequency
in grade3 FL (Swerdlow et al., 2017). BCL6
rearrangement is also present in 5–15% of the
cases (Swerdlow et al., 2017).
Extranodal Marginal Zone Lymphoma
Definition
Extranodal marginal zone lymphoma (extranodal
MZL) is an extranodal lymphoma composed of
heterogeneous small B cells with some cases having characteristic plasmacytic differentiation
(Swerdlow et al., 2017).
Clinical Features
The endometrium is the most common primary
site for marginal zone lymphoma in the female
genital tract (Nasioudis et al., 2017). Yet, uterine
extranodal MZL are exceedingly rare (Kosari
et al., 2005). Extranodal MZL often arises in
association with infection or autoimmune disease
(Magnoli et al., 2016).
Microscopy
Endometrial MZL has nodular architecture composed of small to medium-sized atypical
B lymphocytes. The tumor cells have pale abundant cytoplasm, irregular nuclei with moderately
dispersed chromatin, and inconspicuous nucleoli.
The abundant pale cytoplasm might give the
appearance of monocytoid features. Plasmacytic
differentiation is also present.
The atypical lym phocytes usually present in
the marginal zone area, external to preserved mantle zone areas. The tumor cells may spread out to
form confluent areas that eventually replace most
of the follicles leaving small remnant germinal
centers, which can be evident by negative BCL2
(Swerdlow et al., 2017).
Immunophenotype
The neoplastic cells express B-cell markers CD20
and CD79a. Unlike other CD5-/CD43+ extranodal MZL, endometrial MZL has distinctive features of co-expression CD5 and CD43 (Bennett
et al., 2016). Otherwise, immunohistochemistry is
similar to other extranodal MZL. The tumor cells
are negative for CD10, CD23, cyclin D1, and IgD.
The expression of follicular dendritic cell (FDC)
markers CD21, CD23, and CD35 demonstrates
expanded meshwork of FDCs, corresponding to
colonized follicles (Swerdlow et al., 2017).
Molecular Features
Chromosomal translocation including t(11;18)
(q21;q21), t(1;14)(p22;q32), t(14;18)(q32;q21),
and t(3;14)(p14.1;q32), trisomy of chromosome
3 or 18 are nonspecific but they have been frequently reported in extranodal MZL (Swerdlow
et al., 2017).
References
Al-Katib, A. M., Ebrahim, A. S., Kandouz, M., Zaiem, F.,
Raufi, A., Ebrahim, S., Mohamed, A., Emara, N., &
Gabali, A. M. (2020). Isolation and characterization of
a CD34 + sub-clone in B-cell lymphoma. Oncotarget,
14;11(2), 148–160.
Bennett,J.A.,Oliva,E.,Nardi,V.,Lindeman,N.,Ferry,J.A.,
& Louissaint, A. (2016). Primary endometrial marginal
zone lymphoma (MAL T lymphoma). The American
Journal of Surgical Pathology, 40,1217–1223.
Cao, X.-X., Li, J., Cai, H., Zhang, W., Duan, M.-H., &
Zhou, D.-B. (2017). Patients with primary breast and
primary female genital tract diffuse large B cell lymphoma have a high frequency of MYD88 and CD79B
mutations. Annals of Hematology, 96, 1867–1871.
Chan, J. K., Loizzi, V., Magistris, A., et al. (2005). Clini-
copathologic features of six cases of primary cervical
lymphoma. American Journal of Obstetrics and Gyne-
cology, 193, 866–872.
Dursun, P., Gultekin, M., Bozdag, G., et al. (2005). Pri-
mary cervical lymphoma: Report of two cases and
review of the literature. Gynecologic Oncology, 98(3),
484–489.
Ferry, J., & Young, R. (1997). Malignant lymphoma of the
genitourinary tract. Current Diagnostic Pathology, 4,
145–169.
Freeman, C., Berg, J., & Cutler, S. (1972). Occurrence and
prognosis of extranodal lymphomas. Cancer, 29(1),
252–260.
Kosari, F., Daneshbod, Y., Parwaresch, R., et al. (2005).
Lymphomas of the female genital tract: A study of
Lymphoid and Myeloid Tumors, Pathology of the Vagina 167
https://t.me/med1917
186 cases and review of the literature. The American
Journal of Surgical Pathology, 29(11), 1512–1520.
Magnoli, F., Cimetti, L., Bernasconi, B., et al. (2016).
Primary extranodal marginal cell lymphoma, MALT
type, of the endometrium arising in a patient with
rheumatoid arthritis: Report of a case. International
Journal of Gynecological Pathology, 35, 327–332.
Nasioudis, D., Kampaktsis, P. N., Frey, M., Witkin, S. S., &
Holcomb, K. (2017). Primary lymphoma of the female
genital tract: An analysis of 697 cases. Gynecologic
Oncology, 145, 305–309.
Sun, J., Zhang, J., Ling, Q., Luo, Y., Wu, S., Liang, Z.,
Zhong, D., & Zeng, X. (2015). Primary diffuse large
B-cell lymphoma of the ovary is of a germinal Centre
B-cell-like phenotype. Virchows Archiv, 466,93–100.
Swerdlow, S. H., Campo, E., Harris, N. L., Jaffe, E. S.,
Pileri, S. A., Stein, H., & Thiele, J. (2017). WHO
classification of tumors of hematopoietic and lymphoid
tissues (revised) (4th ed.). IARC: Lyon.
Vang, R., Medeiros, L. J., Fuller, G. N., et al. (2001).
Non-Hodgkin’s lymphoma involving the gynecologic
tract: A review of 88 cases. Advances in Anatomic
Pathology, 8(4), 200–217.
Lymphoid and Myeloid
Tumors, Pathology of the
Vagina
pain, dyspareunia, or urinary frequency. A mass
is less common. Compression of the urinary tract
can occur, resulting in hydronephosis. “B” symptoms are rare.
• Age
Vaginal lymphomas have been reported in
patients over a broad age range (age 22–66,
mean 42 years) (Vang et al. 2000).
• Treatment
These tumors are treated with chemotherapy.
• Outcome
Patients typically present with localized disease, and the prognosis appears favorable
(Höffkes et al. 1995; Vang et al. 2000; Petrillo
et al. 2019).
Macroscopy
There is an ill-defined thickening or induration of
the vaginal wall and adjacent structures such as
the cervix and rectovaginal septum may be
invaded.
L
Raji Ganesan
Birmingham Women’s and Children’s NHS Trust,
Birmingham, UK
Definition
Predominant involvement of the vagina by a
hematolymphoid neoplasm (as opposed to secondary involvement when widespread disease is
present).
Clinical Features
Secondary involvement of the female genital tract
by systemic lymphoma is far more common than
primary lymphoma (the ovary is the most common site in the latter group). Primary vaginal
lymphoma is very rare (Vang et al. 2000; Kosari
et al. 2005; Nasioudis et al. 2017). Presenting
symptoms include abnormal vaginal bleeding,
Microscopy
The vast majority are diffuse large B cell lymphomas (Vang et al. 2000; Kosari et al. 2005;
Nasioudis et al. 2017). The appearance is
described at nodal and other extranodal sites.
Sclerosis and a “sarcomatoid appearance” have
been described as a predominant feature in primary cervical and vaginal tumors (Harris and
Scully 1984).
Immunophenotype and Molecular
Features
This is the same as for nodal lymphomas.
Differential Diagnosis
The main differential diagnoses are undifferentiated carcinomas, neuroendocrine carcinomas,
168 Lymphoid and Myeloid Tumors, Pathology of the Vagina
https://t.me/med1917
undifferentiated sarcomas, and melanomas. The
presence of dyshesive large cells should stimulate
the inclusion of lymphoid markers in the discriminatory immunohistochemical panel as this is critical
in making the correct diagnosis.
References and Further Reading
Harris, N. L., & Scully, R. E. (1984). Malignant lymphoma
and granulocytic sarcoma of the uterus and vagina.
A clinicopathologic analysis of 27 cases. Cancer,
53(11), 2530–2545.
Höffkes, H. G., Schumann, A., Uppenkamp, M.,
Teschendorf, C., Schindler, A. E., Parwaresch, R., &
Brittinger, G. (1995). Primary non-Hodgkin’s lym-
phoma of the vagina. Case report and review of the
literature. Annals of Hematology, 70(5), 273–276.
Kosari, F., Daneshbod, Y., Parwaresch, R., Krams, M., &
Wacker, H. H. (2005). Lymphomas of the female genital tract: A study of 186 cases and review of the
literature. American Journal of Surgical Pathology,
29(11), 1512–1520.
Nasioudis, D., Kampaktsis, P. N., Frey, M., Witkin, S. S., &
Holcomb, K. (2017). Primary lymphoma of the female
genital tract: An analysis of 697 cases. Gynecologic
Oncology, 145(2), 305–309.
Petrillo, M., Fara, A. M., Fedeli, M. A., Fozza, C., Cossu,
A., Gulotta, A., Dessole, F., Piana, A., Capobianco, G.,
Tanda, F., & Dessole, S. (2019). Primary extranodal
vaginal non-hodgkin lymphoma: Diagnostic pitfalls
and therapeutic challenges. Histology and Histopathol-
ogy, 34(7), 723–730.
Vang, R., Medeiros, L. J., Silva, E. G., Gershenson, D. M.,
& Deavers, M. (2000). Non-Hodgkin’s lymphoma
involving the vagina: A clinicopathologic analysis of
14 patients. American Journal of Surgical Pathology,
24(5), 719–725.
Соседние файлы в папке Библиотека им академика М.И. Перельмана