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
Malignant Mesenchymal and Mixed Tumors 179
https://t.me/med1917
Vicus, D., Finch, A., Cass, I., Rosen, B., Murphy, J., Fan, I.,
Royer, R., McLaughlin, J., Karlan, B., & Narod, S. A.
(2010). Prevalence of BRCA1 and BRCA2 germ line
mutations among women with carcinoma of the
fallopian tube. Gynecologic Oncology, 118,299–302.
Visvanathan, K., Vang, R., Shaw, P., Gross, A., Soslow, R.,
Parkash, V., Shih, I. M., & Kurman, R. J. (2001). The
American Journal of Surgical Pathology, 35, 1766–1775.
Y okoyama, Y ., Yokota, M., Futagami, M., Mizunuma, H.
(2012). Carcinosarcoma of the fallopian tube: Report of
four cases and review of literatur e. Asia Pac J Clin Oncol,
8(3), 303–11. https://doi.org/10.111 1/j.1743-7563.2011.
01513.x. Epub 2012 Mar 12. PMID: 22897648.
Yokoyama, Y., Futagami, M., Fujimoto, T., Terada, Y.,
et al. (2013). Investigation of the clinicopathological
features of fallopian tube malignancy. Oncology
Reports, 30,79–84.
Wolsk y, R. J., Price, M. A., Zaloudek, C. J., Rabban, J. T.
(2018). Mucosal proliferations in completely examined
fallopian tubes accompanying ovarian low-grade serous
tumors: Neoplastic precursor lesions or normal variants of
benign mucosa? Int J Gyneco l Pathol, 37(3), 262–274.
Malignant Mesenchymal and
Mixed Tumors, Pathology of
the Broad Ligaments and
Other Uterine Ligaments
• Age
Patients are of reproductive age (much younger
than patients with uterine adenosarcoma) (Kao
and Norris 1978).
• Site
Broad ligament. One case arising in the round
ligament, one para-ovarian, and three extrauterine pelvic tumors have been reported.
Most have arisen from endometriosis (Kerner
et al. 1989; Milam et al. 2006).
• Clinical Presentation
Patients present pelvic pain and/or adnexal
mass (Russell et al. 1979).
• Treatment
Patients are treated by hysterectomy with bilateral salpingo-oophorectomy. Radiotherapy or
chemotherapy also may be considered, the latter particularly in patients with inoperable disease (Milam et al. 2006).
• Outcome
Adenosarcoma is associated with better survival
in comparison to other types of broad ligament
sarcomas, particularly leiomyosarcoma. However, recurrence is associated with poor prognosis (Clement and Scully 1978).
M
Isabel Alvarado-Cabrero
Department of Pathology, Mexican Oncology
Hospital, Mexico City, Mexico
Adenosarcoma
Adenosarcoma.
Definition
A tumor composed of a benign epithelial component admixed with a malignant stroma.
Clinical Features
• Incidence
This tumor is extremely rare (Clement and
Scully 1978).
Macroscopy
There is a mass lesion of uterine ligaments.
Microscopy
These biphasic tumors contain epithelial and stromal components identical to those in the uterus.
The epithelium is morphologically benign, usually endometrioid or tubal-type (Fig. 1) and lines
leaf-like processes of stroma or occurs at scattered
glands within a sarcomatous stroma. The stromal
component is a low-grade sarcoma (Clement and
Scully 1978).
Molecular Features
Not clinically relevant.
180 Malignant Mesenchymal Tumors, Pathology of the Fallopian Tube
https://t.me/med1917
Malignant Mesenchymal and Mixed Tumors, Pathology of the Broad Ligaments and Other Uterine Ligaments, Fig. 1 (a) Broad ligament adenosarcoma. Low-
power view. Biphasic tumor composed of benign
Differential Diagnosis
The differential diagnosis of broad ligament
adenosarcoma includes the following: adenofibroma, carcinosarcoma, or endometrial stromal
sarcoma with glandular diffe rentiation.
Sarcomas of the Broad Ligament
Sarcomas (leiomyosarcoma being the most common one) are extremely rare in this location.
References and Further Reading
Clement, P. B., & Scully, R. E. (1978). Extrauterine meso-
dermal (Mullerian) adenosarcoma: A clinicopathologic
analysis of five cases. American Journal of Clinical
Pathology, 69, 276–283.
Kao, G. F., & Norris, H. J. (1978). Benign and low-grade
variants of mixed mesodermal tumor (adenosarcoma)
of the ovary and adnexal region. Cancer, 42,
1314–1324.
Kerner, H., Lichtig, C., & Beck, D. (1989). Extrauterine
Mullerian adenosarcoma of the peritoneal meso-
thelium: A clinicopathologic and electron micro-
scopic study. Obstetrics and Gynecology, 73,
510–513.
Milam, M. R., Atkinson, J. B., & Currie, J. L. (2006).
Adenosarcoma arising in inguinal endometriosis.
Obstetrics and Gynecology, 108, 753–755.
Russell, P., Slavutin, L., Laverty, C. R., et al. (1979).
Extrauterine mesodermal (Mullerian) adenosarcoma.
A case report. Pathology, 11, 557–560.
epithelium and malignant stroma. (b) Broad Ligament
adenosarcoma. High-power view. The epithelium is benign
of tubal type and the stroma is low-grade
Malignant Mesenchymal
Tumors, Pathology of the
Fallopian Tube
Isabel Alvarado-Cabrero
Department of Pathology, Mexican Oncology
Hospital, Mexico City, Mexico
Sarcomas of the Fallopian Tube
Sarcomas of the fallopian tube.
Synonyms
Malignant mesenchymal tumors.
Definition
A malignant tumor of connective tissues
(mesodermal or mesenchymal cells).
Leiomyosarcoma is the most common type in
this location (Xia et al. 2018).
Clinical Features
• Incidence
Sarcomas of the fallopian tube are exceedingly
rare. Because of its low incidence, literature on
Malignant Mesenchymal Tumors, Pathology of the Fallopian Tube 181
https://t.me/med1917
fallopian tube sarcomas is limited only to case
reports (You et al. 2018).
• Age
The age at diagnosis varies from 21 to
70 years with a median of 47 years (Zagouri
et al. 2011).
• Site
Fallopian tube.
• Clinical Presentation
Because this neoplasm is characterized as the
growth of a progressively painless mass, it is
easily overlooked until the mass is sufficiently
large. The clinical signs and symptoms are
usually nonspecific and include lower abdom-
inal pain and pelvic pressure (Mariani
Malignant Mesenchymal Tumors, Pathology of the
Fallopian Tube, Fig. 1 Leiomyosarcoma of the fallopian
tube. The tumor cells are spindle shaped with eosinophilic
cytoplasm. The nuclei are fusiform
et al. 2005).
• Treatment
Primary treatment of fallopian tube sarcomas
overlaps the standard surgical approach to
epithelial fallopian tube or ovarian carcino-
mas, including total abdominal hysterec-
tomy, bilateral salpingo-oophorectomy,
omentectomy, peritone al washin g, and
cytoreduction, of all resectable tumor masses
and accurate ins pection of the peritoneal sur-
faces a nd visceral organs (Mariani
et al. 2005).
• Outcome
They are considered the most lethal of all
gynecological malignancies with high meta-
static potential, frequent recurrences, and
Malignant Mesenchymal Tumors, Pathology of the
Fallopian Tube, Fig. 2 Leiomyosarcoma of the fallopian
tube. The tumor cell nuclei are pleomorphic with an atypical mitotic figure
cancer-related deaths (Xia et al. 2018).
(Wang et al. 2017), rhabdomyosarcoma, and
Macroscopy
synovial sarcoma (Zagouri et al. 2011).
M
Most tumors are solid masses with tan to hemorrhagic cut surfaces. The average tumor size is
8 cm (range 3.5–11 cm) (Wang et al. 2017).
Microscopy
Leiomyosarcoma is hypercellular and composed
of atypical spindle cells with hyperchromatic
nuclei (Fig. 1). The diagnosis is based on findings
including coagulative necrosis, increased mitotic
activity, or cellular atypia (Fig. 2). Other reported
fallopian tube sarcomas include liposarcoma
Immunophenotype
The most commonly used immunomarkers for diagnostic and prognostic purposes in the evaluation of
soft tissue sarcomas are: smooth muscle actin,
desmin, myoglobin, Myo-D1, TLE-1, vimentin,
cytokeratin, and epithelial membrane antigen
(EMA), among others (Zagouri et al. 2011).
Molecular Features
Not clinically relevant.
182 Malignant Mixed Epithelial-Mesenchymal Tumors, Pathology of the Fallopian Tube
https://t.me/med1917
Differential Diagnosis
The differential diagnosis includes carcinosarcomas (which display epithelial components), extraintestinal gastrointestinal stromal
tumors, and extragenital sarcomas (Wang
et al. 2017).
References and Further Reading
Mariani, L., Quattrini, M., Galati, et al. (2005). Primary
leiomyosarcoma of the fallopian tube: A case report.
European Journal of Gynaecological Oncology, 26,
333–335.
Wang, L., Luo, R., Xiong, Z., Xu, J., & Fang, D. (2017).
Primary pleomorphic liposarcoma of fallopian tube
with recurrence: A case report and review of the liter-
ature. Open Med, 12, 485–488.
Xia, L. F., Ye, S., Shen, X., et al. (2018). Primary
leiomyosarcoma of the fallopian tube: Three case
reports and review of the literature. Taiwanese Journal
of Obstetrics & Gynecology, 57, 456–461.
You, D., Wang, Q., Jiang, W., et al. (2018). Primary
leiomyosarcoma of the fallopian tube. A case report
and literature review. Medicine, 97(17), e0536.
Zagouri, F., Dimopoulus, A. M., et al. (2011). Sarcomas of
the fallopian tube: Disentangling a rare entity.
Onkologie, 134, 132–138.
Malignant Mixed EpithelialMesenchymal Tumors,
Pathology of the
Fallopian Tube
Isabel Alvarado-Cabrero
Department of Pathology, Mexican Oncology
Hospital, Mexico City, Mexico
Definition
A biphasic tumor with malignant mesenchymal
and benign epithelial components.
Clinical Features
• Incidence
This tumor is exceedingly uncommon
(Gallardo and Prat 2009).
• Age
Adenosarcoma of the f allopian tube occurs in
all age groups, but it is most common in
women after menopause (McCluggage
2010).
• Site
Fallopian tube.
• Clinical Presentation
No clinical features are specific; the tumor may
present as a pelvic or uterine mass (Pinto and
Howitt 2016).
• Treatment
Total abdominal or laparoscopic-assisted vaginal hysterectomy with bilateral salpingooophorectomy is the treatment of choice for
this tumor. There is no standardized chemotherapy, hormonal therapy, or radiation therapy
in adenosarcoma (Gallar do and Prat 2009;
Pinto and Howitt 2016).
• Outcome
Adenosarcoma is in general of low malignant
potential, except when accompanied by sarcomatous overgrowth, wall invasion, or recurrence (pelvic wall) (Gollard et al. 1995).
Macroscopic Appearance
Adenosarcoma
Adenosarcoma.
Synonyms
Mesodermal adenosarcoma.
Some tumors present in the fimbriated end or as an
intratubal polypoid mass (Scully et al. 1998).
Microscopic Appearance
The microscopic features of adenosarcoma of the
fallopian tube are the same as those of the more
Melanocytic Tumors, Pathology of the Cervix 183
https://t.me/med1917
common adenosarcomas of the endometrium and
ovary (Gallardo and Prat 2009).
Melanocytic Tumors,
Pathology of the Cervix
Immunophenotype
In most adenosarcomas with a low-grade stromal
component without sarcomatous overgrowth, the
stromal element expresses estrogen receptor, progesterone receptor, CD10, and WT1 is negative
with p53 wild type and exhibits a low MIB1
proliferation index (Pinto and Howitt 2016).
Molecular Features
Not clinically relevant.
Differential Diagnosis
The particular entities considered in the differential
diagnosis vary with the type of adenosarcoma. At
the very low end of the spectrum, the differential
diagnosis in cludes primarily benign entities, such as
the adenofibroma. In the presence of high-grade
sarcoma and /or sarcomatous over growth, the
main diagnosis to rule out is carcinosarcoma
(McCluggage 2010).
References and Further Reading
Gallardo, A., & Prat, J. M. (2009). Mullerian
adenosarcoma. A clinicopathologic and immunohisto-
chemical study of 55 cases challenging the existence of
adenofibroma. The American Journal of Surgical
Pathology, 33, 278–288.
Gollard, R., Kosty, M., Bordin, G., Wax, A., & Lacey,
C. (1995). Two unusual presentationsof Mullerian adeno-
sarcoma: Case reports, literature review, and treatment
considerations. Gynecologic Oncology, 59, 412–422.
McCluggage, W. G. (2010). Mullerian adenosarcoma of
the female genital tract. Advances in Anatomic Pathol-
ogy, 17, 122–129.
Pinto, A., & Howitt, B. (2016). Uterine Adenosarcoma.
Archives of Pathology & Laboratory Medicine, 140,
286–290.
Scully, R. E., Young, R. H., & Clement, P. B. (1998). Atlas
of tumor pathology. Tumors of the ovary, maldeveloped
gonads, fallopian tube, and broad ligament (3rd ed.).
AFIP: Washington, DC.
Noorah Almadani2and Lynn Hoang
1
Anatomical Pathology, Vancouver General
Hospital, Vancouver, BC, Canada
2
University of British Columbia, Vancouver, BC,
1,2
Canada
Definition
Melanocytic tumors of the cervix are melanocytic
proliferations which range from benign to malignant. In the cervix, they consist primarily of blue
nevi and melanoma. There are several hypotheses
on the melanocyte’s origin in the cervix, which
includes transformation from schwannian cells,
metaplastic transformation from endocervical epithelium, and migration of neural crest cells
(Parada et al. 2012).
Clinical Features
• Incidence
The incidence of cervical pigmented lesions is
low. Although some propose that the incidence
of blue nevi is underestimated. Around 77 cases
of cervical blue nevi have been reported in the
literature. Only 5% of primary melanoma
occurs in the gynecological tract, and much
more commonly in the vulva (75%) and vagina
(19%), although some have estimated rates as
high as 2–9%. Radiation, estrogen, and highrisk HPV infections have been considered
possible risk factors for melanoma (Benson
and Tan 2000;Khooetal.1991;Rohwedder
et al. 2002).
• Age
Blue nevi usually affect middle-aged women
(Report 2004), while melanoma affects postmenopausal adults between age 60 and
70 years (Pusceddu et al. n.d.).
• Treatment
There is no standard protocol for the best management approach (Cantuaria et al. 1999;
M
184 Melanocytic Tumors, Pathology of the Cervix
https://t.me/med1917
Pusceddu et al. n.d.). The majority of early
stage cases are treated similar to cervical car-
cinoma, with hysterectomy with or without
bilateral salpingo-oophorectomy, bilateral pel-
vic lymph node dissection, and upper
vulvectomy with clear surgical resection mar-
gins (Mihajlovic et al. 2012; Piura 2008;
Pusceddu et al. 2012). The use of adjuvant
radiotherapy is variable.
• Outcome
Blue nevi are benign. Cervical melanoma typ-
ically spread beyond the cervix with involve-
ment of the vagina (Cantuaria et al. 1999;
Pusceddu et al. n.d.). The overwhelming
majority of patients present with FIGO stage
II disease or higher at time of diagnosis
(Pusceddu et al. n.d.). Prognosis is dismal
with median survival of 12 months (Cantuaria
et al. 1999; Deshpande and Munshi 2001).
Macroscopy
Blue nevi present as solitary or multiple brown or
black lesions, ranging in size from 0.1–2cmin
size. Cellular blue nevus can form a pedunculated
mass. Melanoma typically presents as an exophytic and ulcerated cervical mass ( <1cmto
9 cm) (Pusceddu et al. n.d.). Pigmentation is
observed in some of these tumors, but they can
be amelanotic (Deshpande and Munshi 2001;
Pusceddu et al. n.d.).
Microscopy
Cervical common blue nevi have histologic features common to their cutaneous counterparts,
variably pigmented spindled dendritic melanocytes intermix with oval, epithelioid melanocytes
in the dermis with no mucosal involvement (Tran
et al. 2014). Mitosis and cytologic atypia are
absent. Cellular blue nevus, a variant of blue
nevus, would have a component of common
blue nevus, as well as distinct cellular areas composed of spindled to oval melanocytes, which
have been described in the cervix (Eskue et al.
2010; Hagiwara et al. 2005; Parada et al. 2012;
Rodriguez and Ackerman 1968).
Melanoma of the cervix shows a wide variety
of architectural patterns, which includes nests,
fascicles of spindle-shaped cells, sheets of epithelioid cells, or less commonly small, round, or clear
cells. High mitotic activity, varying degrees of
nuclear pleomorphism, and intracytoplasmic melanin are commonly found (Eskue et al. 2010;
Hagiwara et al. 2005; Parada et al. 2012;
Rodriguez and Ackerman 1968). The diagnosis
of primary melanoma of cervix requires the presence of melanocytes in the adjacent epithelium
and exclusion of metastatic melanoma from
elsewhere.
Immunophenotype
Common blue nevus and cellular blue nevi are
positive for S-100, MART-1, Melan-A, and variably immunoreactive to HMB-45. Melanoma is
typically positive for SOX10, S-100, MelanA,
and HMB-45, and it is negati ve for cytokeratin
and smooth muscle markers. Immunophenotype
of cervical melanoma, however, is the same as that
from other primary sites. Hence exclusion of
metastasis of melanoma should be considered in
the diagnosis.
Molecular Features
In contrast to cutaneous melanoma, BRAF mutations are very rare in mucosal melanomas (Udager
et al. 2017). Mutations and/or copy number
increases of KIT have been reported in up to
40% of mucosal melanomas. In a recent study,
PD-L1 expression was observed in 33% of cervical melanoma (Yu et al. 2020).
Differential Diagnosis
Due to the common absence of pigmentation in
cervical melanoma, the diagnosis of amelanotic
melanoma may be difficult to distinguish from
rhabdomyosarcoma, leiomyosarcoma, mixed
Müllerian tumor, adenocarcinoma, and poorly differentiated squamous cell carcinoma. Like tumors
Melanocytic Tumors, Pathology of the Vagina 185
https://t.me/med1917
elsewhere, cervical melanomas may be mistaken
for sarcomas and poorly differentiated carcinomas.
References and Further Reading
Benson, R. J., & Tan, L. T. (2000). Radiation-induced
malignant melanoma of the cervix. Clinical Oncology
(Royal College of Radiologists (Great Britain)), 1,
2234–2237.
Cantuaria, G., Angioli, R., Nahmias, J., Estape, R., &
Penalver, M. (1999). Primary malignant melanoma of
the uterine cervix: Case report and review of the literature. Gynecologic Oncology, 75, 170–174.
Deshpande, A. H., & Munshi, M. M. (2001). Primary malig-
nant melanoma of the uterine cervix: Report of a case
diagnosed by cervical scrape cytology and review of the
literature. Diagnostic Cytopathology, 2, 5108–51 1 1.
Eskue, K., Prieto, V. G., & Malpica, A. (2010). Cellular
blue nevus of the uterus: A case reportand review of the
literature. International Journal of Gynecological
Pathology, 2, 9583–9586.
Hagiwara, T., Kaku, T., Kobayashi, H., Hirakawa, T., &
Nakano, H. (2005). Coexisting vulvar malignant melanoma and blue nevus of the cervix. Gynecologic Oncol-
ogy, 9(9), 519–520.
Khoo, U. S., Collins, R. J., & Ngan, H. Y. (1991). Malignant
melanoma of the female genital tract. A report of nine
cases in the Chinese of Hong Kong. Pathology, 2, 3312.
Mihajlovic, M., Vlajkovic, S., Jovanovic, P., & Stefanovic,
V. (2012). Primary mucosal melanomas: A comprehensive review. International Journal of Clinical and
Experimental Pathology, 5(8), 739–753.
Parada, D., Peña, K. B., & Riu, F. (2012). Coexisting
malignant melanoma and blue nevus of the uterine
cervix: An unusual combination. Case Reports in
Pathology, 986, 542–547.
Piura, B. (2008). Management of primary melanoma of the
female urogenital tract. The Lancet Oncology, 9, 973–981.
Pusceddu, S., et al. (2012). A literature overview of primary
cervical malignant melanoma: an exceedingly rare cancer.
Critical Re views in Oncology/Hematology, 81, 185–195.
Pusceddu, S., et al. (n.d.). A literature overview of primary
cervical malignant melanoma: An exceedingly rare cancer. Critical Reviews in Oncology/Hematology, 8,
1185–1195.
Report, C. (2004). Common blue nevus of the uterine
cervix. Applied Immunohistochemistry & Molecular
Morphology, 12,79–82.
Rodriguez, H. A., & Ackerman, L. V. (1968). Cellular blue
nevus: Clinicopathologic study of forty-five cases.
Cancer, 2, 1393–
Rohwedder, A., Philips, B., Malfetano, J., Kredentser, D.,
& Carlson, J. A. (2002). Vulvar malignant melanoma
associated with human papillomavirus DNA: Report of
two cases and review of literature. The American Jour-
nal of Dermatopathology, 2, 4230–4240.
Tran, T. A. N., et al. (2014). The spectrum ofgrossly visible
pigmented lesions in the uterine cervix: A prospective
1405.
study. International Journal of Gynecological Pathol-
ogy, 33,89–99.
Udager, A. M., et al. (2017). Gynecologic melanomas:
A clinicopathologic and molecular analysis. Gyneco-
logic Oncology, 14, 7351–7357.
Yu, Y., et al. (2020). Predictive biomarkers and tumor
microenvironment in female genital melanomas:
A multi-institutional study of 55 cases. Modern Pathol-
ogy, 3(3), 138–152.
Melanocytic Tumors,
Pathology of the Vagina
Saimah Arif
Princess Alexandra Hospital NHS Trust, Harlow,
Essex, UK
Mucosal Melanoma
Synonyms
Mucosal lentiginous melanoma; Vaginal melanoma; Vulvovaginal melanoma (those that also
involve the vulva).
Definition
This is a malignant melanocytic neoplasm.
Clinical Features
Vaginal melanomas are rare tumors, accounting
for 3–5% of vaginal cancers and <1% of all
melanomas. They are less common than vulvar
melanomas. Exposure to ultraviolet radiation is
most likely not a causative factor. Usual presenting features include a mass +/ pigmentation
and vaginal bleeding.
• Age
Most occur in postmenopausal patients (mean
age of 60).
• Site
The most common site is the lower third of the
vagina and the anterior and lateral walls are
most commonly involved.
• Treatment
Surgery (resection of the primary tumor +/
lymph node dissection) is the primary treatment
M
186 Melanocytic Tumors, Pathology of the Vagina
https://t.me/med1917
modality. Radiotherapy may be used in an adjuvant setting or as primary therapy for unresectable tumors. Targeted therapy based on the
presence of BRAF and KIT mutations is possible.
Immune checkpoint inhibitors may be considered for those with PDL1 expression (Wang
et al. 2020).
• Outcome
Melanomas of the genital mucosa are more
aggressive than their cutaneous counterparts
and have a poorer prognosis. The cutaneous
melanoma-staging system should be applied to
vaginal melanomas. The prognosis is relatively
poor, partly due to the aggressiveness of the
tumor and partly because patients are often at
Melanocytic Tumors, Pathology of the Vagina,
Fig. 1 Vaginal melanoma. Nodular masses of tumor
cells are present in this ulcerated melanoma
an advanced stage at presentation. Five year
survival rates of 10–30% have been reported.
Lymph node status is the most important predictor for disease-specific survival (Kirschner
et al. 2013). Poor prognostic features include
increased tumor thickness, ulceration, high
mitotic count, and positive resection margins
(Udager et al. 2017). The outcome with systemic immunotherapy for metastatic mucosal
melanoma is poorer than with cutaneous
melanoma.
Macroscopy
Typically, the lesions present as large, pigmented,
ulcerated, nodular/polypoid masses which often
involve the cervix.
Microscopy
The appearances are similar to those of mucosal
melanomas at other sites (Fig. 1). The nodular
subtype is most common (Wohlmuth et al. 2020).
Both epithelioid and spindle cells may be present.
Occasionally, small or naevoid cells may predominate. Melanin is usually present within both the
tumor cells and macrophages (Fig. 2). Within the
epithelium, a lentiginous growth of single atypical
melanocytes in the basal layer is present, sometimes with nests or confluent growth.
Immunophenotype
The tumor cells are positive with S100, SOX10,
HMB45, and melan-A.
Melanocytic Tumors, Pathology of the Vagina,
Fig. 2 Vaginal melanoma. Melanin pigment granules are
clearly visible within both tumor cells and macrophages
Molecular Features
The mutational burden is relatively low compared
to cutaneous melanoma. NRAS and cKIT mutations have been described in vaginal melanoma,
facilitating targeted therapies. BRAF mutations
are less common than in cutaneous melanoma
(Aulmann et al. 2014; Rouzbahman et al. 2015;
Wang et al. 2020).
Differential Diagnosis
Benign melanocytic lesions will not demonstrate
the typical features of malignancy described
above. Immunostaining can help with determining differentiation in a poorly differentiated
Melanocytic Tumors, Pathology of the Vulva 187
https://t.me/med1917
tumor. Metastatic melanoma is excluded by the
presence of an in situ component.
References and Further Reading
Aulmann, S., Sinn, H. P., Penzel, R., Gilks, C. B., Schott,
S., Hassel, J. C., Schmidt, D., Kommoss, F.,
Schirmacher, P., & Kommoss, S. (2014). Comparison
of molecular abnormalities in vulvar and vaginal melanomas. Modern Pathology, 27(10), 1386–1393.
Kirschner, A. N., Kidd, E. A., Dewees, T., & Perkins, S. M.
(2013). Treatment approach and outcomes of vaginal
melanoma. International Journal of Gynecological
Cancer, 23(8), 1484–1489.
Rouzbahman, M., Kamel-Reid, S., Al Habeeb, A., Butler,
M., Dodge, J., Laframboise, S., Murphy, J., Rasty, G.,
& Ghazarian, D. (2015). Malignant melanoma of vulva
and vagina: A histomorphological review and mutation
analysis–a single-center study. Journal of Lower Gen-
ital Tract Disease, 19(4), 350–353.
Udager, A. M., Frisch, N. K., Hong, L. J., Stasenko, M.,
Johnston, C. M., Liu, J. R., Chan, M. P., Harms, P. W.,
Fullen, D. R., Orsini, A., Thomas, D. G., Lowe, L., &
Patel, R. M. (2017). Gynecologic melanomas:
A clinicopathologic and molecular analysis. Gyneco-
logic Oncology, 147(2), 351–357.
Wang,H.Y.,Wu,X.Y.,Zhang,X.,Yang,X.H.,Long,
Y.K.,Feng,Y.F.,&Wang,F.(2020).Prevalence
of NRAS mutation, PD-L1 expression and amplification, and overall survival analysis in 36 primary
vaginal melanom as. The Oncologist, 25(2),
e291–e301.
Wohlmuth, C., Wohlmuth-Wieser, I., May, T., Vicus, D.,
Gien, L. T., & Laframboise, S. (2020). Malignant melanoma of the vulva and vagina: A US population-based
study of 1863 patients. American Journal of Clinical
Dermatology, 21(2), 285–295.
Definition
Atypical genital nevus (AGN) is a benign
melanocytic tumor located in the genital area,
characterized by an atypical but reproducible
histology.
Clinical Features
• Incidence
Pigmented genital lesions occur in about
10–12% of women; however, genital nevi are
noted in only about 2% of the population
(Cengiz et al. 2015; Hosler et al. 2008).
• Age
AGN occur usually in young adults, with a
median age of 26 years (Gleason et al. 2008).
• Site
The most common sites in order of frequency
are labium minor, labium majus, clitoris, and
vestibulum followed by mons pubis and peri-
neum (Cengiz et al. 2015; Clark et al. 1998).
A predilection for mucosal areas has been
noted in girls younger than 10 years.
• Treatment
Treatment beyond a biopsy to establish the
diagnosis is not necessary. In some instances,
a conservative but complete excision may be
recommended for cases that are partially
biopsied.
• Outcome
AGNs are benign lesions. Like any nevi, they
can recur when incompletely excised; how-
ever, they do not progress or spread at distant
sites.
M
Melanocytic Tumors,
Pathology of the Vulva
Aleodor Andea
Department of Pathology, University of
Michigan, Ann Arbor, MI, USA
Atypical Genital Nevus
Synonyms
Atypical melanocytic nevus of the genital type;
Genital nevus.
Macroscopy
Some AGNs are circumscribed and uniformly
pigmented flat or papular lesions; however, often
they demonstrate an atypical clinical presentation
with hyperpigmentation and incre ased size of up
to 2 cm in diameter which prompts a biopsy
(Brenn 2011).
Microscopy
At scanning microscopy, AGNs are symmetric
and well circumscribed. The junctional component takes the form of large melanocytic nests
with irregular size and shape. Frequently the
nests have a horizontal arrangement and oval
188 Melanocytic Tumors, Pathology of the Vulva
https://t.me/med1917
Melanocytic Tumors, Pathology of the Vulva,
Fig. 1 AGN at low power, AGNs are usually well
circumscribed. In the junction, the melanocytes are
arranged as large discohesive nests with horizontal
arrangement and fusion along the dermo-epidermal junction. A thick band of fibrosis is seen in the superficial
dermis
shape with parallel distribution and fusion along
the dermo-epidermal junction (Fig. 1). Pagetoid
spread of single melanocytes in the upper reaches
of the epidermis is not prominent and when present is limited to the center of the lesion. There is
often adnexal involvement either as nests or as
single melanocytes. Often the nests show
discohesion with clefting between the nests and
adjacent epidermis. The junctional melanocytes
are usually epithelioid with abundant cytoplasm,
vesicular nuclei, and prominent nucleoli. Cytologic atypia in the form of angulated and hyperchromatic nuclei may be seen (Fig. 2). In the
lamina propria or superficial dermis, there is usually a thick band of fibrosis. When a dermal component is present it may show cytologic atypia in
the superficial dermis; however, deeper, the melanocytes show usually a bland morphology, maturation with dermal descent, and no mitotic activity
(Fig. 3; Brenn 2011; Christensen et al. 1987;
Gleason et al. 2008).
Immunophenotype
AGNs express melanocytic markers including
Melan-A, SOX10, and S100. Similar to other
types of nevi, HMB-45 show s gradual loss of
staining with depth, Ki-67 shows a low labeling
index in the dermis or lamina propria, and p16
Melanocytic Tumors, Pathology of the Vulva,
Fig. 2 AGN the melanocytes are epithelioid with abun-
dant cytoplasm, vesicular nuclei, and occasional visible
nucleoli. There is cytologic atypia noted in the form of
angulated and hyperchromatic nuclei
shows uniform expression, features that can be
used in the differential diagnosis with vulvar
melanoma.
Molecular Features
Most AGNs are characterized by the presence of
BRAF p.V600E mutations. This can help differentiate them from vulvar melanomas which tend
to demonstrate KIT and TP53 gene mutations and
wild BRAF (Cohen et al. 2004; Tseng et al. 2014;
Yelamos et al. 2016).
Differential Diagnosis
Due to the presence of atypical features, the most
important diagnosis of AGN is with vulvar melanoma. Table 1 outlines the differentiating features. Melanomas tend in older individuals and
on histologic examination show more prominent
single cells in the mucosa or epidermis with
confluent growth along the dermo-epidermal
junction and diffuse pagetoid spread. If there is
an invasive melanoma component, it usually
shows lack of maturation, cytologic atypia, and
mitotic activity.
Genital Melanotic Macule
Synonyms
Genital lentiginosis; Genital melanosis.
Соседние файлы в папке Библиотека им академика М.И. Перельмана