Pathology of endometrial ablation failures: a clinicopathologic study of 164 cases.

Endometrial ablation is a minimally invasive alternative to hysterectomy for abnormal uterine bleeding. Although the failure rate is low, continued bleeding or development of pelvic pain after ablation does occur. We analyzed the clinicopathologic features of 164 hysterectomy specimens after endometrial ablation, 19 of which were performed for indications other than failed ablation (control cases). Pathologic findings included: dense fibrosis and hyalinization of the endometrial surface ablative necrosis within the uterine cavity and adherent to the endometrial surface, persistent months after ablation; uterine cavity lined by superficial, large, congested, patent blood vessels with atherosis; ablation changes present only in the lower uterine segment; and residual endometrium present in the cornual regions. Patients with ablative necrosis underwent subsequent hysterectomy sooner than those without such debris (median of 5 vs. 23 mo, respectively). Patients with superficial abnormal vessels were also more likely to have a shorter ablation-hysterectomy interval than those without (median of 2 vs. 18 mo, respectively). Patients with associated adenomyosis or prior tubal ligation were significantly more likely to have continued bleeding. Possible sources of continued abnormal bleeding or pelvic pain include: the presence of ablative necrosis or superficial abnormal blood vessels, although the association did not reach statistical significance in this study; incomplete ablation, affecting only the lower uterine segment or sparing the cornual region; tubal endometriosis after ligation; and endometrial regeneration via adenomyosis.

Unusual nonrefractile eosinophilic crystal in breast ducts in a patient with invasive mucinous carcinoma.

A 72-year-old, G4P2 white woman presented with a recent abnormal mammogram showing a nodule at 8 o'clock of her right breast and indeterminate calcification in the subareolar region. An initial stereotactic core followed by wide local excision and sentinel node biopsy showed a pT1aN0(sn)M(na) low-grade invasive mucinous carcinoma. In dilated benign ducts, adjacent to the carcinoma, numerous eosinophilic, nonrefractile crystals were identified.

Unilateral pelvic mass presenting in postmenopausal patients: report of two unusual cases.

We encountered 2 unusual cases of polypoid endometriosis presenting as unilateral ovarian masses. The first was benign and was found in a 57-year-old postmenopausal patient; the second case gave rise to well-differentiated endometrioid carcinoma in an 80-year-old patient. The second patient also had a superficially invasive endometrioid adenocarcinoma of the endometrium arising in a background of complex atypical hyperplasia. Intraoperative evaluation was requested in both cases.

Tubal metaplasia of the endometrium with cytologic atypia: analysis of p53, Ki-67, TERT, and long-term follow-up.

Tubal metaplasia of the endometrium may occasionally display cytologic atypia (atypical tubal metaplasia) resembling serous carcinoma or endometrial intraepithelial carcinoma. Although atypical tubal metaplasia is presumed to be reactive or degenerative in etiology, its clinical significance is unknown. In this study, we investigated atypical tubal metaplasia in regard to its immunoexpression of p53, Ki-67, and human telomerase reverse transcriptase (TERT), and its long-term clinical outcome. A total of 63 cases of atypical tubal metaplasia and 200 cases of endometrial samples with typical tubal metaplasia were followed for a mean of 64 and 61 months, respectively. Of the 63 atypical tubal metaplasia cases, formalin-fixed, paraffin-embedded tissue sections from 16 cases were immunostained with antibodies to p53, Ki-67, and TERT. Sections from 13 cases of uterine serous carcinoma were also stained for TERT as control. After long-term follow-up, 5% of patients in the atypical tubal metaplasia group developed hyperplasia without atypia compared with 4% of patients in the control group (P=0.44), whereas 3% in the atypical tubal metaplasia group developed atypical hyperplasia or carcinoma compared with 2% in the control group (P=0.44). p53 immunoreactivity was either focal and weak or negative in all cases of both atypical and typical tubal metaplasia (P>0.05). Ki-67 immunoreactivity was present in 0-5% of cells in 94% of both atypical and typical tubal metaplasia (P>0.05). TERT immunoexpression was absent in all 16 cases of atypical tubal metaplasia, but present in all 13 cases of uterine serous carcinoma (P<0.0001). Our study indicates that atypical tubal metaplasia displays an immunostaining pattern similar to otherwise typical tubal metaplasia of the endometrium, and distinct from uterine serous neoplasms. The presence of atypical tubal metaplasia in endometrial samplings does not increase the risk of developing endometrial hyperplasia or malignancy.

Vascular plexiform leiomyoma mimicking uterine tumor resembling ovarian sex cord tumor.

Leiomyomata are common benign smooth muscle neoplasms with a usually easily recognizable histologic pattern. However, there is a wide variety of subtypes described in the literature, characterized by predominance of a particular distinct histologic pattern. Here we describe a case of a highly vascular leiomyoma with a prominent plexiform pattern and cords and tubules of epithelioid cells that mimics a uterine tumor resembling an ovarian sex cord tumor.

A 46 XY phenotypic female adolescent with bilateral gonadal tumors consisting of five different components.

46 XY gonadal dysgenesis patients often develop gonadal tumors, including gonadoblastoma and other types of germ cell tumors. We report a case of a 16-year-old female adolescent with primary amenorrhea and a right adnexal mass. Subsequent study revealed that she is a 46 XY phenotypic female adolescent with complete gonadal dysgenesis and with no alterations of the sex-determining region Y gene. Microscopic examination of the gonads revealed bilateral gonadoblastoma mixed with dysgerminoma and mature teratoma. The tumor in the right gonad was also mixed with yolk sac tumor and immature teratoma with rhabdomyoblastic components, mimicking adult rhabdomyoma and rhabdomyosarcoma. No metastasis in the regional lymph nodes was identified and the patient is disease free 15 months postsurgery. The complexity of the tumorigenesis in this case indicates that the gonadal cells in gonadal dysgenesis are extremely unstable and highly tumorigenic. This tumorigenesis is not necessarily associated with sex-determining region Y gene alterations; therefore, it reinforces the recommendation of gonadectomy for gonadal dysgenesis patients, regardless of the sex-determining region Y gene status.

Association of ovarian hyperthecosis with endometrial polyp, endometrial hyperplasia, and endometrioid adenocarcinoma in postmenopausal women: a clinicopathological study of 238 cases.

Ovarian hyperthecosis, a source of estrogen, may occur in postmenopausal women. In this study, we evaluated the possible association of ovarian hyperthecosis with endometrial polyp, endometrial hyperplasia, and endometrioid adenocarcinoma in postmenopausal women. Our study consisted of 238 postmenopausal women: 108 with endometrioid adenocarcinoma and 130 without endometrial carcinoma. The International Federation of Gynecology and Obstetrics system was used to grade endometrioid adenocarcinoma. Within the endometrioid adenocarcinoma cases, 48 (44.4%) were grade 1, 46 (42.6%) were grade 2, and 14 (13.0%) were grade 3. Among the noncancer cases, 71 (54.6%) had atrophic endometrium, 32 (24.6%) had endometrial polyp, and 27 (20.8%) had endometrial hyperplasia. The frequency of ovarian hyperthecosis in patients with endometrial polyp (46.9%), endometrial hyperplasia (55.6%), and grade 1 (43.8%), grade 2 (54.3%), and grade 3 (57.1%) endometrioid adenocarcinoma was each significantly higher than that in patients with atrophic endometrium (23.9%), supporting an association of these lesions with ovarian hyperthecosis in postmenopausal women. There was no statistically significant difference in the rate of ovarian hyperthecosis among patients with endometrial polyp, endometrial hyperplasia, and grade 1, grade 2, and grade 3 endometrioid adenocarcinoma. Our study indicates that ovarian hyperthecosis with its resultant risk factor of hyperestrinism may contribute to the pathogenesis of endometrial polyp, endometrial hyperplasia, and endometrioid adenocarcinoma in postmenopausal women. Although some studies show that grade 3 endometrioid adenocarcinoma has different genetic/molecular changes from its lower-grade counterparts, our study suggests that endometrioid adenocarcinoma of all grades may share the common risk factor of hyperestrinism.

Comparative Sensitivities and Specificities of Antibodies to Breast Markers GCDFP-15, Mammaglobin A, and Different Clones of Antibodies to GATA-3: A Study of 338 Tumors Using Whole Sections.

GATA-3 is a transcription factor that has recently been identified by immunohistochemistry to be highly expressed in urothelial and breast carcinomas (CAs). We sought to determine the potential utility of GATA-3 in identifying metastatic breast CA, and to compare its utility with the standard breast markers, GCDFP-15, and mammaglobin A. We identified an archival series of 338 formalin-fixed paraffin-embedded whole-tissue sections of various CAs. Using standard immunohistochemical (IHC) techniques we used mouse monoclonal antibodies to GATA-3 (clones L50-823, HG3-31), GCDFP-15 (23A3), and mammaglobin A (31A5). Both clones of GATA-3 showed positivity in 96% of non-triple-negative breast carcinomas (TNBCs), L50-823 and HG3-31, demonstrating expression in 87% and 63% of TNBCs, respectively; GCDFP-15 and mammaglobin A were expressed in 69% and 61% of non-TNBCs, respectively, and 10% and 17%, of TNBCs, respectively. The L50-823 clone manifested a lower specificity in identifying breast CAs (84%) than did the HG3-31 clone (97%). Both monoclonal antibodies to GATA-3 are very sensitive reagents for the identification of breast CA, surpassing antibodies to GCDFP-15 and mammaglobin A, and offer a significant improvement in identifying TNBCs. However, the L50-823 clone showed a lower level of specificity, which may qualify its utility in the setting of CAs of unknown primary.

Localized amyloidosis of the vulva with and without vulvar intraepithelial neoplasia: report of a series.

Localized primary cutaneous amyloidosis is uncommon in Europe and North America and is infrequently reported in the English literature. The constituents of such deposits have not been previously examined; this series characterizes amyloid deposits in localized vulvar amyloidosis and their association with vulvar intraepithelial neoplasia. All biopsies and excisions of vulva over 18 months were reviewed. Cases with suspected amyloidosis were retrieved after institutional review board approval. Twenty cases mimicking amyloidosis were selected as controls. All study and control cases were stained with Congo red. Four Congo red-positive study cases were studied by liquid chromatography-tandem mass spectrometry. Of 27 Congo red-positive study cases, 25 were then examined by immunohistochemical stains with antibodies to cytokeratin 5 (CK5) and cytokeratin 14 (CK14). Of 149 cases reviewed, 26 localized and 1 systemic vulvar amyloidosis were identified. Liquid chromatography-tandem mass spectrometry analysis of the deposits revealed unique peptide profile consistent with CK5 and CK14. Immunohistochemical staining with antibodies to CK5 and CK14 also detected these components in the deposits. The vulvar deposit of systemic amyloidosis consisted of amyloid light chain (λ)-type amyloid deposit. All control cases were negative for Congo red. Keratin-associated amyloid materials (CK5 and CK14) were found to be unique in localized vulvar amyloidosis. Leakage of keratins from the basal layer of the epithelium into the superficial dermis may have been the possible source of the deposits. It appears to be associated with both high-grade and low-grade vulvar intraepithelial neoplasias and, rarely, lichen sclerosus, seborrheic keratosis, and benign vulvar skin.

Incidental gynecologic neoplasms in morcellated uterine specimens: a case series with follow-up.

Laparoscopic hysterectomy with morcellation (LHM) is considered a safe and less invasive alternative to other hysterectomy techniques by shortening postoperative hospital stay and patient recovery. Sparse incidental gynecologic neoplasms after LHM have been reported; however, the frequency and subsequent follow-up have not been systematically investigated in a large case series. We aimed to determine the frequency and types of incidental findings after LHM with clinical outcomes. An electronic chart review was conducted searching all cases of LHM performed within 5 years to determine the incidence of unexpected gynecologic neoplasms and subsequent peritoneal disease. Patient demographics, prior preoperative investigation, and subsequent follow-up were investigated. For comparison, the overall frequency of pertinent uterine neoplasms was noted during the study period. Of the 352 cases of LHM identified, 3 harbored unsuspected malignancies, an incidence of 0.9%. Four variant smooth muscle tumors (1.1%) and 5 benign non-smooth muscle neoplasms (1.4%) were identified at the time of initial morcellation. Two cases of subsequent peritoneal "implanted" leiomyoma were identified (0.6%). Of malignant or atypical mesenchymal neoplasms diagnosed at our institution during the study period, 8.6% were diagnosed in a morcellated specimen. There is a clinically important risk of occult malignant or atypical neoplasms in morcellated uterine specimens. Proper pathologic evaluation of malignant or atypical uterine neoplasms is limited when a uterus is morcellated. Patients undergoing morcellation procedures are also potentially at risk for dissemination of disease. Clinicians and patients should be aware of these risks when discussing surgical options for hysterectomy.

Arias-Stella reaction of the cervix: The enduring diagnostic challenge.

BACKGROUND: The Arias-Stella reaction is a hormone-related atypical endometrial change characterized by hypertrophy and vacuolization of glandular epithelial cells, associated with marked nuclear pleomorphism, enlargement, and hyperchromasia. When presenting in extra-uterine sites, the differentiation of Arias-Stella changes from other more ominous clear cell lesions may pose significant difficulties. CASE REPORT: We report a case of an endocervical clear cell lesion incidentally discovered during a prenatal visit of a young pregnant woman. Interpretation of the pathological findings was complicated by the small size and fragmentation of the specimen. CONCLUSIONS: Recognition of Arias-Stella reaction in extra-uterine sites, especially in young women, is critical to avoid misdiagnosis of this innocuous lesion as clear cell adenocarcinoma. Attention to cellular and nuclear detail, as well as careful consideration of the clinical scenario, is crucial for establishment of the correct diagnosis.

Liesegang-like rings in lactational changes in the breast.

Liesagang-like rings (LR) are periodic structures with equally spaced radial striations formed by a process that involves diffusion, nucleation, flocculation or precipitation, and supersaturation. Being more common in vitro, on rare occasions also reported in vivo in association with inflammatory or cystic lesions and confused with parasites or calcification on needle aspirates. The current paper documents that LRs may be seen in noncystic and noninflammatory changes of the breast.

"Surface epithelial changes" in uterine endometrioid carcinoma mimicking micropapillary serous borderline tumor of ovary: report of two cases and review of the literature.

We encountered two cases of endometrioid carcinoma of uterus with extensive surface epithelial changes (SECs) mimicking serous borderline tumor (SBT) of the ovary. The first case was a well-differentiated endometrioid carcinoma arising in a background of complex atypical hyperplasia. The second case was moderately-differentiated endometrioid carcinoma with squamous and mucinous differentiation. The SECs comprised of thin microapapillae without hierarchal branching, lined by cuboidal cells with eosinophilic cytoplasm and mild to moderate nuclear atypia. These areas were reminiscent of SBTs of ovary, micropapillary type. This report expands the existing spectrum of SECs. Serous borderline tumor of ovary like surface epithelial changes could be misleading if present in an endometrial biopsy or curettings. Therefore, knowledge of this morphologic variation is important.

Merkel cell carcinoma expresses K homology domain-containing protein overexpressed in cancer similar to other high-grade neuroendocrine carcinomas.

Merkel cell carcinoma is an uncommon and aggressive primary cutaneous neuroendocrine carcinoma with a high rate of recurrence and metastasis. Optimal management is controversial; consequently, it is imperative to identify the signaling pathways involved in the pathogenesis of Merkel cell carcinoma so that effective therapeutic targeting agents can be developed. We previously reported that K homology domain-containing protein overexpressed in cancer is expressed in high-grade neuroendocrine carcinomas of the lung and extrapulmonary small cell carcinomas. The K homology domain-containing protein overexpressed in cancer (KOC), also known as L523S and IMP-3, is an insulin-like growth factor II messenger RNA-binding protein that promotes tumor cell proliferation by enhancing insulin-like growth factor II protein expression. Expression of KOC in Merkel cell carcinoma has not been investigated. We studied 20 Merkel cell carcinomas by immunohistochemistry using a monoclonal antibody against L523S/KOC. Of 20 Merkel cell carcinomas, 18 (90%) overexpressed KOC, with 11 (55%) overexpressing KOC in greater than 90% of tumor cells, 3 (15%) overexpressing KOC in 50% to 90% of tumor cells, 3 (15%) overexpressing KOC in 10% to 50% of tumor cells, and 1 (5%) overexpressing KOC in less than 10% of tumor cells. The immunostaining intensity was variable, with moderate to strong staining in 14 cases and weak staining in the remaining 4. Extent of expression of K homology domain-containing protein overexpressed in cancer predicted metastasis (P = .04) and was weakly correlated with increased tumor size (P = .08). In conclusion, Merkel cell carcinoma expresses K homology domain-containing protein overexpressed in cancer with an expression pattern similar to high-grade neuroendocrine carcinomas of the lung and extrapulmonary small cell carcinomas. We propose K homology domain-containing protein overexpressed in cancer as a potential target molecule for the treatment of high-grade neuroendocrine carcinomas, irrespective of anatomical location, and a potential marker to predict metastatic disease.

CD44 expression is a feature of prostatic small cell carcinoma and distinguishes it from its mimickers.

Small cell neuroendocrine carcinoma of the prostate is a rare variant of prostatic cancer that shares morphologic similarity with prostatic adenocarcinoma of Gleason 5 pattern. It has also been considered morphologically and immunohistochemically indistinguishable from small cell neuroendocrine carcinomas of other origins. CD44 is a cell-surface molecule proposed to identify cancer stem/progenitor cells in prostate cancer. We performed immunohistochemical study for CD44 expression in 11 cases of prostatic small cell neuroendocrine carcinoma and compared its patterns of expression with 73 cases of prostatic adenocarcinoma and 47 cases of small cell neuroendocrine carcinomas of other organs. Strong and diffuse membrane staining for CD44 was observed in 100% of the prostatic small cell neuroendocrine carcinomas. In conventional adenocarcinomas of the prostate, positive staining was only seen in rare, scattered tumor cells; and CD44 staining was negative in most of the small cell neuroendocrine carcinomas of nonprostate origin. The difference in CD44 expression between small cell neuroendocrine carcinomas of the prostate and those of other organs are statistically significant (P < .001). Our study demonstrates the utility of immunohistochemical staining for CD44 in distinguishing prostatic small cell neuroendocrine carcinoma from its mimickers including prostatic adenocarcinoma of Gleason 5 pattern and small cell neuroendocrine carcinomas of other organs. CD44 is the first marker that shows a high degree of tissue/organ specificity for small cell neuroendocrine carcinomas. Because CD44 is a putative marker of prostate cancer stem cells, the strong and diffuse expression of CD44 and the lack of expression of prostate luminal differentiation markers androgen receptor and prostatic specific antigen in prostatic small cell neuroendocrine carcinomas suggest that the tumor cells may retain cancer stem cell features.

Gnatho-thoracopagus conjoined twins with near di-symmetry: a case report of an unusual form of conjoined twinning.

The term gnatho-thoracopagus was used previously to describe a remote case of conjoined twins with union involving the mandible. Few reported cases of this type of union exist in the literature. A case of ventrally conjoined twins, with union involving the mandible and near di-symmetry, is presented here and compared with similar previously reported cases. The presented case represents an example of prosopo-thoracopagus, an intermediate between cephalopagus and thoracopagus conjoined twins, although this case does have unique variations.

Mucinous tubular and spindle cell carcinoma of the kidney with sarcomatoid differentiation.

We report a unique case of mucinous tubular and spindle cell carcinoma (MTSC) of the kidney with extensive sarcomatoid differentiation, multiple metastases, and a rapidly fatal clinical course. The patient presented with back pain and a pathologic L1 fracture. Diagnostic imaging revealed a large retroperitoneal mass arising from the left kidney and compressing the spinal cord. Radiotherapy and surgery were performed, but the patient died from disease progression three weeks postoperatively. MTSC is a recently recognized entity that is considered to be a low-grade carcinoma with a favorable prognosis. Our case demonstrates that although MTSC is usually a low-grade carcinoma, sarcomatoid differentiation may occur and lead to a fatal course, as in all other types of renal cell carcinomas. Adequate sampling and the exclusion of sarcomatoid differentiation in the spindle cell component are necessary for proper management and prognostication. To our knowledge, this is the first reported case of MTSC with sarcomatoid differentiation and a fatal outcome.