Aims Mucocele-like lesions (MLL) of the breast are rare. MLL associated with flat epithelial atypia (FEA) or atypical ductal hyperplasia (ADH) is classified as MLL with atypia (AtypMLL). We study the upgrade rate and long-term outcomes in AtypMLL, focusing on the extent and type of atypia in needle biopsy (NB). Methods and results AtypMLL in NB specimens from 1 January 2010 to 30 June 2023, were identified. Clinical data and histological findings in NB were recorded. Excision findings and long-term follow-up information were obtained. Statistical analysis was performed. Thirty-four NBs of AtypMLL, 5 (15%) with FEA and 29 (85%) with ADH were identified. Twenty-five out of 27 (93%) excisions revealed no upgrade; 9 were benign, and 16 showed residual ADH/FEA/lobular neoplasia. Two (7.4%) excisions upgraded to carcinoma: one low nuclear grade ductal carcinoma in situ (DCIS) and one histologic grade 2 invasive breast carcinoma, no special type. ADH was architecturally complex, and a significantly higher number of ADH foci were present in NB of two cases with the upgrade (5 and 7 foci, respectively). The ADH foci were significantly lower in the NB without the upgrade (1.79, 95% CI: 1.19, 2.39; P < 0.001 vs. upgrade). The foci of atypia in NBs increased progressively in excisions with benign, atypical and carcinoma findings. Two patients developed breast carcinoma at 6 and 16 months (median 73 months, 6-120 months). Conclusion The upgrade rate of AtypMLL presenting with calcifications depends on the foci and architectural complexity of atypia in NB. The long-term outcome of AtypMLL appears favourable.

The peritoneum is a site for diverse nonneoplastic and neoplastic disease processes, including those encountered in many other organ systems in the body. A recent theory is that Müllerian peritoneal/omental serous carcinoma is a metastasis from a similar tumor of the fallopian tubes, challenging the once-proposed theory that omentum is a part of the secondary Müllerian system and has a role in the pathogenesis of primary serous carcinomas. The metastatic theory applies to serous carcinomas only, not tumors of any other Müllerian cell types. Just being a mere receptacle for metastasis from other organ sites, the notion that the peritoneum and its derivatives are an essential source of primary peritoneal carcinomas remains a valid concept.

Perivascular epithelioid cell tumors (PEComas), rare mesenchymal tumors with myomelanocytic differentiation, can be a diagnostic challenge, often requiring a panel of immunohistochemical markers. Preferentially expressed antigen in melanoma (PRAME) is a relatively new antigen with utility in diagnosing melanomas. This study aimed to survey PRAME expression patterns in the PEComa family of tumors and morphologic mimics. Twenty cases of PEComas and 27 non-PEComas (10 leiomyosarcomas, 3 smooth muscle tumors of uncertain malignant potential [STUMPs], 11 leiomyomas, 1 uterine inflammatory myofibroblastic tumor [IMT], and 2 low-grade endometrial stromal sarcomas [LGESSs]) were stained with PRAME and compared to previously performed HMB45 and Melan-A stains, when available. Tumors showing no or barely perceptible PRAME staining at 10× were considered negative. Tumors were considered positive if there was full nuclear staining evident at 10× in at least one 10× field. Diffuse staining was defined as positivity in at least 80% of tumor nuclei. Overall, PRAME was expressed in 70% of PEComas, with diffuse positivity in 60%. However, PRAME was not specific for PEComas, with immunopositivity in the majority (70%) of uterine leiomyosarcoma cases, though negative in STUMP, leiomyoma, IMT, and LGESS cases. PRAME sensitivity was 70% and specificity was 74%, while HMB45 was more sensitive (90%) and specific (100%), but only 15% of PEComas showed diffuse staining. Melan-A staining was less common than HMB45 or PRAME, with only 18.8% sensitivity but 100% specificity. Among gynecologic PEComas, PRAME was expressed in 75% overall and enriched among malignant cases (85.7% positive). As part of an immunohistochemical panel, PRAME could be useful in the workup of PEComa cases. In the future, PRAME-specific immunotherapies may be beneficial in treating patients with malignant PEComas.

Abstract There have been exceedingly few reports of epidermodysplasia verruciformis (EV) or EV-like lesions in the vulva. We describe the first case series featuring vulvar lesions displaying synchronous EV-like histologic changes and conventional high-grade intraepithelial lesion (VIN 3), a finding hitherto unreported in medical literature. We hypothesized that this could be caused by coinfection with α-HPV and β-HPV genotypes. Cases were retrospectively selected from our institutional archive. Detailed review of clinical information, histologic examination and whole genome sequencing (WGS) were performed in 5 samples from 4 different patients. Three of four patients had a history of either iatrogenic immune suppression or prior immune deficiency, and all featured classic VIN 3 and EV changes within the same lesion. The fourth patient had no history of immune disorders, presented with EV-like changes and multinucleated atypia of the vulva, and was the sole patient without conventional high-grade intraepithelial lesion. By WGS, several uniquely mappable reads pointed towards infection with multiple HPV genotypes including both α-HPVs and β-HPVs. Mutations in genes implicated in cell-mediated immunity, such as DOCK8, CARMIL2, MST1 and others, were also found. Our findings provide novel insight into EV and HPV pathogenesis, vulvar precancerous lesions and expand the clinicopathological spectrum of genetic alterations linked to unconventional immune deficiencies.

Extrauterine Mullerian adenosarcomas (MA) are rare and often associated with endometriosis. We report a 55-yr-old patient seen in consultation for abdominal pain and bloating. Imaging was suggestive of a left adnexal mass and "peritoneal carcinomatosis". Pathological examination of the specimen revealed a MA arising in the left fallopian tube, with sarcomatous overgrowth, diffuse peritoneal involvement and omental "caking". Next-generation sequencing identified a MEIS1-NCOA2 gene fusion, previously unreported in MA.

The metastatic or recurrent potential of localized human papillomavirus-associated endocervical adenocarcinoma (HPVA EAC) is difficult to predict, especially based upon biopsy alone. Recent analyses of small cohorts indicate that high tumor nuclear grade (TNG) and the presence of necrotic tumor debris (NTD) from HPVA EACs in cervical biopsy specimens are highly predictive of nodal metastasis (NM). In the present study, we aimed to investigate how reliably tumoral morphologic features from cervical biopsy specimens predict NM or tumor recurrence (TR) and patient outcomes in a large cohort of endocervical adenocarcinoma patients. A cohort comprised of 397 patients with HPVA EAC treated at 18 institutions was identified, and cervical biopsies were paired with their associated complete tumor resections for a total of 794 specimens. A variety of tumoral histologic features were examined for each paired specimen, including TNG (assessed on a 3-tiered scale of increasing abnormalities-TNG1, TNG2, TNG3) and NTD (defined by the presence of necrotic and apoptotic tumor cells within tumor glandular lumens admixed with granular and eosinophilic amorphous material and inflammatory cells), which were correlated with outcomes. The distribution of TNG in biopsies was as follows: 86 (21.7%) TNG1, 223 (56.2%) TNG2, and 88 (22.2%) TNG3. NTD was identified in 176 (44%) of the biopsy specimens. The sensitivity, specificity, positive predictive value, and negative predictive value of a TNG1 assignment in the biopsy being predictive of the same assignment in the full resection were 0.82 (95% confidence interval [CI]: 0.7-0.9), 0.895 (0.86-0.93), 0.593 (0.48-0.696), and 0.96 (0.94-0.98), respectively. Respective values for an NTD-negative status were 0.89 (95% CI: 0.83-0.92), 0.715 (0.64-0.77), 0.72 (0.65-0.77), and 0.89 (0.83-0.93), respectively. Compared with the other cases in each category, both TNG1 and an NTD-negative status were each significantly associated with lower rates of NM (odds ratio for TNG1=0.245, 95% CI: 0.070-0.857, P=0.0277; for NTD=0.199, 95% CI: 0.094-0.421, P<0.0001) and TR (odds ratio for TNG1=0.225, 95% CI: 0.051-0.987, P=0.0479; for NTD=0.367, 95% CI: 0.171-0.786, P=0.0099) independent of depth of stromal invasion, lymphovascular invasion, tumor size, FIGO stage, and Silva pattern. Overall, 73/379 (19%) cases were both TNG1 and NTD-negative on the biopsy, and none of these 73 cases showed NM (0%), but a single case (1.4%) showed TR. In contrast, among the 324 biopsies with TNG2/3 and/or presence of NTD, 62 (19.1%) had NM, and 41 (12.9%) had TR. In summary, 2 variables in combination (ie, TNG1 and NTD-negative) identified a subset of HPVA EAC patients-∼19%-with a 0% frequency of nodal metastases and only 1.4% frequency of recurrence. Biopsies highly but imperfectly predicted these features. Nonetheless, these findings may potentially be of clinical utility in the risk stratification of patients with HPVA EACs. This may allow some patients with a minimal risk of nodal metastases and TR to be identified at the biopsy phase, thereby facilitating more personalized, possibly less aggressive treatment.

Objective: The aim of this study was to identify the frequency for which a preoperative diagnosis of endometrial intraepithelial neoplasia (EIN) is upstaged to cancer at hysterectomy and sentinel lymph node (SLN) sampling would be indicated.

Penelitian ini di latar belakangi oleh tentang perilaku siswa di ruang lingkup keluarga, sehingga pada masanya kemudian hari peserta didik atau siswa dapat mengamalkan perilaku-perilaku baik sesuai dengan tuntunan Nabiyullah Muhammad SAW. Tujuan penelitian tersebut, ingin menambah pengetahuan tentang potret pendidikan agama islam keluarga siswa SMP Muhammadiyah 8 Tanggulangin di rumahnya. Untuk meningkatkan karakter siswa yang berakhlaqul karimah. Jenis penelitian ini bersifat kualitatif, dengan pendekatan studi kasus. Da-lam memilih dan menentukan subyek penelitian, peneliti menggunakan teknik sampel kontruksi. Adapun teknik pengumpulan data melalui wawancara, observa-si dan dokumentasi. Sedangkan teknik analisis datanya penulis menggunakan teknik analisis Miles dan Huberman.Ada dua yakni reduksi data dan penyajian data. Dari hasil penelitian di atas telah di paparkan bahwa potret pendidikan agama islam keluarga di SMP Muhammadiyah 8 Tanggulangin rata-rata siswanya di didik oleh orangtua asli dengan cara berbagai macam. Ada yang menggunakan dengan cara selalu mengingatkan tanpa ada tindakan dan juga ada yang menggunakan dengan cara memberikan tindakan dan tontonan. Sedangkan faktor yang menyebabkan anak berperilaku baik dan buruk bahwa rata-rata yang menyebabkan siswa SMP Muhammadiyah 8 Tanggulangin Sidoarjo berperilaku buruk karena adanya faktor teknologi yang canggih yang menyebabkan siswa sulit di ingatkan ketika di berikan tugas kewajiban sebagai umat muslim

The endometrium displays a wide spectrum of appearances in both neoplastic and non-neoplastic tissue. Unusual proliferations are not infrequently encountered and may lead to misinterpretation. In this study, we investigated pseudorosette-like proliferations (PLPs) found within the endometrial stroma which, to our knowledge, have not been previously reported. Nineteen endometrial samples with PLPs were identified over a period of 5 yr. Characteristics of the endometrium in which the PLPs were arising as well as patient information were recorded for each case. In addition, residual tissue from 10 of the cases was immunostained for cytokeratin, CD10, smooth muscle actin, S-100, and caldesmon to better characterize the lesions. In all cases the endometrium was in the proliferative phase and none of the patients reported the use of exogenous hormones. In 89% (17 of 19) of the cases, PLPs were present as a single focus; 2 cases showed multiple PLPs. Of the 10 immunostained cases, 90% (9 of 10) showed strong/diffuse staining for smooth muscle actin. Six cases showed negative or weak (1+) staining for CD10, whereas 3 showed moderate (2+) and 1 showed strong (3+) staining. In all cases the PLPs were negative for cytokeratin AE1/AE3, S-100, and caldesmon. These studies suggest that PLPs are benign proliferations with smooth muscle differentiation.

The purposes of this study are to assess the level of interobserver variability in the diagnosis of endometrial carcinomas with clear cells by gynecologic pathologists based purely on their morphologic features and to comparatively describe the cases of putative clear cell carcinoma (CCC) with and without significant interobserver variability. A total of 35 endometrial carcinomas (1 slide per case) were reviewed by 11 gynecologic pathologists (median experience: 10 y) from 11 North American institutions. The cases were selected from the files of 3 institutions on the basis of the presence of at least focal clear cells and had previously been classified as a variety of histotypes at these institutions. Diagnoses were rendered in a blinded manner and without predetermined diagnostic criteria or categories. The kappa values between any pair of observers ranged from 0.18 to 0.69 (combined 0.46), which was indicative of a "moderate" level of interobserver agreement for the group. Subgroups of "confirmed CCC" [cases diagnosed as such by at least 8 (73%) of the 11 observers, n = 14] and "possible CCC" (cases diagnosed as CCC by >= 1 but < 8 observers, n = 13) were compared with regard to a variety of semiquantified morphologic features. By combining selected morphologic features that displayed statistically significant differences between the 2 groups on univariate analyses, the following approximate morphologic profile emerged for the confirmed CCC group: papillae with hyalinized cores in >= 33% of the lesion, clear cells in >= 33% of the lesion, hyperchromasia in >= 33% of the lesion, the absence of nuclear pseudostratification in > 3 cells on the papillae, the absence of nuclear pseudostratification in glands in >= 33% of the lesion, the absence of diffuse grade 3 nuclei, the absence of long and slender papillae in >= 33% of the lesion, and glands and papillae lined by cuboidal to flat, noncolumnar cells. In a backward stepwise logistic regression analysis, features from the profile that predicted the confirmed CCC group included: (1) absence or minimality of diffuse sheets of grade 3 nuclei [P = 0.025; 95% confidence interval (CI), 0.0266-0.363]; (2) absence or minimality of nuclear stratification in glands and papillae (P = 0.040; 95% CI, -0.228 to -0.0054); and (3) glands and papillae lined by cuboidal to flat, noncolumnar cells (P = 0.008; 95% CI, 0.0911-0.566). The 2 groups displayed significant overlap regarding a wide variety of features, and no single case displayed a full complement of potentially diagnostic features. Morphologic patterns associated with cases with very high levels of interobserver variability (defined as cases with >= 4 different diagnoses rendered for them, n = 9) included the near-exclusive or exclusively solid pattern of clear cells (3/9) and glandular/papillary proliferations whose only CCC-like feature was the presence of clear cells (2/9). In conclusion, the diagnosis of endometrial carcinomas with clear cells by gynecologic pathologists is associated with a moderate level of interobserver variability. However, there is a morphologic profile that characterizes cases that gynecologic pathologists more uniformly classify as CCC, and the presence of these features is supportive of a CCC diagnosis in an endometrial carcinoma with clear cells. Cases that display broad and significant qualitative deviations from the aforementioned profile should prompt the consideration of a diagnosis other than CCC.