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Pseudomyxoma-type Invasion in Gastrointestinal Adenocarcinomas of Endometrium and Cervix: A Report of 2 Cases
Summary: This paper presents a clinicopathologic and immunohistochemical report of 2
gastrointestinal-type tumors, one in the endometrium and the other in the cervix. Both
showed extensive invasion into the pelvic structures with acellular mucin, identical to
pseudomyxoma but in the absence of appendiceal or ovarian tumors. Case 1 was an 81-
yr-old female with a Stage III endometrial gastrointestinal-type adenocarcinoma who
had had an endometrial polyp with intestinal metaplasia 4 yr previously. Case 2 was a
68-yr-old female with Stage IIIB endocervical gastrointestinal-type adenocarcinoma.
Both were associated with a pseudomyxoma type of invasion, which in the endometrial
case was transmural through the myometrium, and in the cervical case involved
parametria, pelvic floor, and lymph nodes. Immunohistochemically, both tumors had a
gastrointestinal phenotype coexpressing cytokeratins 7 and 20, CDX2, villin, MUC2,
MUC5AC, and MUC6 and were negative for human papillomavirus, analyzed by realtime
polymerase chain reaction. The first case exemplifies intestinal endometrial
metaplasia as a precursor lesion of the rare gastrointestinal type of adenocarcinoma and
also proves its progression into carcinoma. The second case exemplifies the highly
aggressive nature of cervical invasion forming mucin lakes. Extensive pseudomyxoma in
the uterus and cervix was associated with high clinical stages with marked
lymphovascular invasion and lymph node metastase
Perivascular epithelioid cell (PEC) tumors of the uterus: a clinicopathologic study of two cases with aggressive features
We report the clinicopathologic, immunohistochemical and ultrastructural features of two unusual tumors of the uterus composed of spindle and epithelioid cells strongly positive for HMB45. The two patients of 56 and 48 years of age had, respectively, hemoperitoneum and abnormal uterine bleeding. Morphologically, both tumors showed atypia and extensive necrosis. The neoplastic cells express immunohistochemically both melanogenesis (HMB45) and smooth muscle markers (actin). Ultrastructural analysis showed the presence of intracytoplasmic membrane-bound granules. We viewed these neoplasms as perivascular epithelioid cell (PEC) tumors with aggressive features. Follow-up has shown the death of one patient whereas the other is alive without disease 36 months after the surgery. The two patients were evaluated for signs of tuberous sclerosis complex, and findings were negative
AN IMMUNOHISTOCHEMICAL STUDY OF MORULES IN ENDOMETRIOID LESIONS OF THE FEMALE GENITAL TRACT: CD10 IS A CHARACTERISTIC MARKER OF MORULAR METAPLASIA.
Purpose: To analyze immunohistochemically morules in endometrioid lesions to show that CD10 is a sensitive marker for morular metaplasia.
Experimental Design: Immunohistochemical analysis of 53 instances of morular metaplasia comprising 1 cyclic endometrium and 52 endometrioid lesions associated with focal glandular complexity corresponding to 9 polyps, 4 atypical polypoid adenomyomas, 24 complex endometrial hyperplasias (18 with and 6 without atypia), 12 grade 1 endometrioid adenocarcinomas in early clinical stages of both uterus and ovary, and three ovarian adenofibromas. Immunohistochemistry in paraffin sections was done for CD10, beta-catenin, estrogen and progesterone receptors, and cytokeratins 5-6, 7, 8,13,18,19, 20, and 34 beta-E12.
Results: Morules were negative for estrogen and progesterone receptors and had beta-catenin positive nuclei. Cytokeratins 8, 18, 19 were positive; cytokeratins 7 and 20 were negative; and cytokeratins 5-6, 13, and 34 beta-E12 were weakly positive. All cases revealed strongly positive membranous CD10 staining in morules, which was absent in glands. CD10 positivity allowed easy identification of morules at low power in various types of surgical specimens and in curettings. CD10 also highlighted early morular metaplasia in glandular epithelium. In cases associated with squamous, keratinizing metaplasia, CD10 discriminated between both types of metaplasia.
Conclusions: CD10 staining represents a useful marker of morules in endometrioid neoplasms of the female genital tract, permitting identification of lesions usually associated with an attenuated malignancy. Considering the immunohistochemical and genetic similarities of morules in tumors of different organs, it is likely that this marker may be also useful to diagnose morular metaplasia in similar neoplasms of extragenital locations
Pregnancy luteoma with granulosa cell proliferation: An unusual hyperplastic lesion arising in pregnancy and mimicking an ovarian neoplasia
A pregnancy luteoma (PL) was incidentally found at a term cesarean section in a 27-year-old black woman without any endocrine abnormality. The lesion involved only the left ovary; it had a nodular and focal pseudoalveolar growth pattern and was associated with areas of tubular sertoliform component, consistent with granulosa cell proliferation. Immunohistochemistry revealed a diffuse positivity to Inhibin A, CD99, cytokeratin and vimentin. The ultrastructure was typical of steroid-producing cells. PL is a tumor-like lesion arising in pregnant women and often misdiagnosed as a neoplastic lesion; awareness of this rare entity and its differential diagnoses may avoid unnecessary surgery in young patients
Adult extrarenal Wilms tumor of the uterus with teratoid features.
The present article reports for the first time a case of an extrarenal teratoid Wilms tumor in the uterus of a 62-year-old woman. It had triphasic histology with epithelial areas composed of metanephric tubules harboring glomerular structures, adamantine patterns, neural type rosettes, blastema, and a primitive, myxoid type stroma. Abundant heterologous elements such as cartilage, striated muscle, squamous epithelium, and an alpha fetoprotein and TTF1-positive early endodermal epithelium were also present. Immunohistochemistry in Wilms tumor areas showed positivity for markers also indicative of peripheral primitive neuroectodermal tumors such as neuron-specific enolase, CD99, and CD56. However, nuclear positivity for Wilms tumor antigen together with the presence of glomeruli and the absence of endometrioid tumor areas and the organoid arrangement of tissues excluded peripheral primitive neuroectodermal tumors, carcinosarcoma, and teratoma, respectively. Although the diagnosis of female genital tract Wilms tumors is difficult in cases where glomerular structures are lacking, it should be considered because these neoplasms have a better therapeutic response than peripheral primitive neuroectodermal tumors and carcinosarcoma
Adenocarcinoma of the Lung Metastatic to the Ovary With a Signet Ring Cell Component
A nonsmoker 45-year-old woman, presented with a solid right ovarian mass.
Microscopic examination revealed heterogeneous histology with tubular formations
and extensive signet ring cell component that resembled the usual appearance of
metastatic gastric carcinoma to the ovary. Moreover, the histology also showed
solid nests of cells with a microvacuolated basophilic cytoplasm similar to those
found in adenosquamous cervical carcinoma of glassy cell type. However, analysis
of the patient's past history revealed a lung adenocarcinoma, diagnosed 4 years
before, which prompted an immunohistochemical differential diagnosis, showing a
strong expression for TTF-1 and Napsin A. A cervical primary was excluded taking
into account both macroscopic findings and the negative expression of PAX8 and
absence of human papillomavirus-related marker p16. This confirmed the pulmonary
origin of ovarian tumor despite its heterogeneous morphology. This is the first
reported case of ovarian metastatic lung adenocarcinoma, with a signet ring cell
component and solid nests, mimicking both metastatic gastric carcinoma and
adenosquamous carcinoma of glassy cell type
Perivascular epithelioid cell (PEC) tumors of the uterus: a clinicopathologic study of two cases with aggressive features
We report the clinicopathologic, immunohistochemical and ultrastructural features of two unusual tumors of the uterus composed of spindle and epithelioid cells strongly positive for HMB45. The two patients of 56 and 48 years of age had, respectively, hemoperitoneum and abnormal uterine bleeding. Morphologically, both tumors showed atypia and extensive necrosis. The neoplastic cells express immunohistochemically both melanogenesis (HMB45) and smooth muscle markers (actin). Ultrastructural analysis showed the presence of intracytoplasmic membrane-bound granules. We viewed these neoplasms as perivascular epithelioid cell (PEC) tumors with aggressive features. Follow-up has shown the death of one patient whereas the other is alive without disease 36 months after the surgery. The two patients were evaluated for signs of tuberous sclerosis comple
A multicentric European study testing the reproducibility of WHO classification of endometrial hyperplasia with a proposal of a simplified working classification for biopsy and curettage specimens
Sertoli Cell Tumor With Benign Peritoneal Implants Associated With Gonadoblastoma
We present a unique case of bilateral gonadoblastoma in a 23-year-old patient with Swyer syndrome. The gonadoblastoma on both sides underwent synchronous neoplastic transformation, into a stage I germinoma in the right streak gonad and a highly differentiated Sertoli cell tumor in the left one. The latter was associated with a myriad of microscopic, Sertoli cell implants on the peritoneal surface, which were considered benign as they had a high grade of differentiation, minimal proliferative activity, and an absence of invasion. Most probably, the pathogenesis of this abdominal dissemination was iatrogenic, with implantation occurring mechanically as a result of the multiple laparoscopic biopsies performed on both of the streak gonads 2 months before the abdominal surgery. The pathogenesis of other benign abdominal implants is discussed.We present a unique case of bilateral gonadoblastoma in a 23-year-old patient with Swyer syndrome. The gonadoblastoma on both sides underwent synchronous neoplastic transformation, into a stage I germinoma in the right streak gonad and a highly differentiated Sertoli cell tumor in the left one. The latter was associated with a myriad of microscopic, Sertoli cell implants on the peritoneal surface, which were considered benign as they had a high grade of differentiation, minimal proliferative activity, and an absence of invasion. Most probably, the pathogenesis of this abdominal dissemination was iatrogenic, with implantation occurring mechanically as a result of the multiple laparoscopic biopsies performed on both of the streak gonads 2 months before the abdominal surgery. The pathogenesis of other benign abdominal implants is discussed
CD10 is a characteristic marker of tumours forming morules with biotin-rich, optically clear nuclei that occur in different organs.
Recently, Chiarelli et al.1 have demonstrated that CD10 immunoreactivity represents a useful marker of morules in endometrioid lesions of the female genital tract, allowing identification of various low-grade lesions which are associated with these nodular structures. Cytologically, morules exhibit bland cells lacking intercellular bridges and keratinization and express neither high-molecular-weight keratins2–5 nor involucrin.6 They are not related to human papillomavirus infection6 and are thus different from both squamous metaplasia and carcinoma.1 Morules with a characteristic nuclear clearing have been reported in endometria,ovarian endometrioid tumours,colorectal adenomas and carcinomas,13–15 gastric polyps,16 gallbladder adenomas,17 pulmonary blastomas, low-grade adenocarcinomas of fetal lung type, some papillary lung carcinomas,18–24 pancreatoblastomas25,26 and, finally, in the cribriform-morular variant (C-MV) of papillary thyroid carcinomas.2–5,27–29 The so-called ‘peculiar nuclear clearing’ so frequently found in these morules is due to biotin-rich intranuclear inclusions which ultrastructurally have the appearance of thread-like fibrils and consequently should not be misinterpreted as intranuclear cytoplasmic pseudoinclusions or as viral inclusion bodies.2,3,15,19,30,31
In order to demonstrate the usefulness of CD10 in the diagnosis of morular metaplasia in neoplasms in extragenital locations, the immunoexpression of CD10 and β-catenin was studied in seven cases of tumours containing morules with cells displaying biotin-rich optically clear nuclei (BROCN; BROCN-family tumours), corresponding to four instances of CM-V of papillary thyroid carcinoma (one of them in the setting of familial adenomatous polyposis), one case of low-grade adenocarcinoma of fetal lung type, one case of pulmonary blastoma and one pancreatoblastoma in a child with Beckwith–Wiedemann syndrome (Figure 1). Immunohistochemistry was performed on paraffin sections using a universal secondary antibody kit that used a peroxidase-conjugated labelled-dextran polymer (Dako EnVision Peroxidase/diaminobenxidene; Dako, Glostrup, Denmark), in order to avoid misinterpreting endogenous biotin or biotin-like activity in the cell cytoplasm or nuclei as immunopositivity.32 All cases revealed strong CD10 membranous positivity (clone 56C6, dilution 1:10, microwave oven, Tris—ethylenediamine tetraaceticacid; NovoCastra, Newcastle-upon-Tyne, UK) in morules (Figure 1), with some cytoplasmic staining, probably due to diffusion. As a result, CD10 positivity allowed easy identification of morules at low power in the different samples. CD10 immunopositivity also outlined the luminal borders of the neoplastic cells in the glandular formations of all tumours. Aberrant nuclear expression of β-catenin (β-catenin-1, 1:300, microwave oven; Dako) was detected only in neoplastic cells of all samples examined (Figure 1). Squamous metaplasia was negative for CD10, and a membranous but no nuclear pattern of reactivity for β-catenin was seen in a case of the diffuse sclerosing variant (DSV) of papillary thyroid carcinoma concurrently studied as a control
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