Jing Yu

Ovarian immature teratomas are rare malignant germ cell tumors composed of immature embryonal tissues, most commonly neuroepithelium, and account for less than 1% of all ovarian teratomas. Cytologic diagnosis is challenging because of overlapping morphologic features with other high‐grade malignant neoplasms and the limited utility of immunohistochemistry. Herein, we report two cases of high‐grade ovarian immature teratomas with metastatic immature neuroepithelial components in young women of childbearing age, emphasizing the cytologic findings, immunophenotypic features, histologic grading, and clinical course.

Objective: This study assesses the effectiveness of Magee Equation 3 (ME3) in predicting response to neoadjuvant chemotherapy (NACT) and its prognostic value. Methods: In total, 263 clinical stage I to III estrogen receptor (ER)–positive, human epidermal growth factor receptor 2 (HER2)–negative breast cancers diagnosed between 2014 and 2020 were assessed for response to NACT. Pathologic complete response (pCR) was defined as no invasive carcinoma in the breast or regional lymph nodes. Results: The pCR rate for the 4 different categories of ME3 scores (25 to <31, and ≥31) was 0% (0 of 44), 4% (4 of 96), 10% (7 of 68), and 31% (17 of 55), respectively. The ME3 score inversely correlated with residual cancer burden (RCB) score (Pearson correlation coefficient, –0.374; P < .001; 95% CI, –0.473 to –0.265). The pCR group also had a lower rate of multifocality (P = .007) and smaller tumor size (P = .008). Patients who achieved pCR (RCB-0) experienced favorable outcomes. In patients with residual disease after NACT, worse recurrence-free survival (RFS), distant recurrence-free survival (DRFS), overall survival (OS), or breast cancer–specific survival (BCSS) was noted for patients with a pretherapy ME3 score greater than 25. In the group with substantial residual disease (RCB-3), an increasing ME3 score was associated with significantly worse RFS (hazard ratio [HR], 1.103; 95% CI, 1.038-1.171), DRFS (HR, 1.086; 95% CI, 1.020-1.156), OS (HR, 1.069; 95% CI, 1.002-1.140), and BCSS (HR, 1.088; 95% CI, 1.002-1.182) in the multivariable analysis. The RCB index and posttherapy grade were also prognostic in the RCB-3 group. Conclusions: The ME3 score is predictive of response to neoadjuvant chemotherapy and is prognostically informative, particularly for RCB-3 cases.

Objective: We examined the utility of preferentially expressed antigen in melanoma (PRAME) immunohistochemistry (IHC) in distinguishing breast angiosarcoma from benign or atypical vascular lesions (AVLs) of the breast. Methods: There were 26 breast angiosarcomas (24 radiation related and 2 primary), 6 radiation-related AVLs of the breast, and 16 other benign vascular lesions of the breast retrieved from our institutional archive and stained with PRAME IHC. Results: Twenty-four of 26 (92%) breast angiosarcomas were positive for PRAME with moderate to strong staining intensities (median HScore, 255 [range, 90-300]), while 0 of 22 benign or atypical vascular lesions of the breast were PRAME positive (sensitivity, 92.3% [95% CI, 75.9%-98.6%]; specificity, 100% [95% CI, 85.1%-100%]); c-MYC was positive in all angiosarcoma cases but showed weak staining in several cases (median HScore, 155 [range, 30-280]). PRAME was negative in 1 of 2 primary angiosarcomas and negative in only 1 of 24 secondary angiosarcomas of the breast. None of the benign or atypical vascular lesions was stained with PRAME. Conclusions: It appears that PRAME expression occurs in a high proportion of radiation-related angiosarcomas and not in benign breast vascular lesions or AVLs. PRAME IHC is diagnostically useful in distinguishing benign from malignant vascular proliferations in patients with a history of radiation to the breast.

MammaPrint (MP) is a multigene assay utilized for prognostic and predictive use in early stage ER+/HER2-negative breast cancer (BC). There is limited data on MP correlation to histopathologic variables, including multivariable model Magee Equations (MEs). We compared pathologic variables to MP on 365 ER+/HER2-negative BCs in the adjuvant setting. Further, we analyzed MP and ME results in 26 core biopsy-proven ER+/HER2-negative BCs subjected to neoadjuvant chemotherapy (NACT). Post-NACT response was assessed by residual cancer burden (RCB) score. In the adjuvant cohort (n=365), high-risk (HR) MP correlated with high Nottingham score, low progesterone receptor H-score, ductal morphology, high Ki-67 index, and high ME score. In the neoadjuvant cohort (n=26), 24 were MP-HR and 2 were MP low-risk (MP-LR). The 2 MP-LR cases correlated with average ME scores of ≤25 and showed RCB scores of 2 or 3. Of the 24 MP-HR, 2 showed RCB-0 or RCB-1. Average ME>25 was seen in both of these cases and 7 others corresponding to an RCB-0 and RCB-1 rate of 22% (2 of 9) with ME>25 compared with 8% (2 of 24) with MP-HR. Lack of significant benefit from NACT (RCB-2 or RCB-3) was accurately predicted by average ME≤25 in 17 of 26 cases (65%) compared with only 2 of 26 cases (8%) with MP-LR. MP correlates with aggressive histopathologic features. While both MP and ME identified cases with robust chemotherapeutic response, MP overpredicted cases that would benefit. Therefore, MEs may more accurately predict response to NACT.

Objectives: The objective of this study was to evaluate SOX17, a transcription factor from the Sry high-mobility group–related box superfamily, as a diagnostic marker to determine site of origin using both whole-tissue sections and tissue microarrays (TMAs). Methods: SOX17 immunohistochemistry was performed on gynecologic and nongynecologic tissues (N = 1004) using whole-tissue sections and both internally constructed and commercially available TMAs. SOX17 nuclear reactivity was scored as positive or negative on the whole-tissue sections and using the semiquantitative H score method on TMAs. Results: Using both whole-tissue sections and TMAs, SOX17 was positive in 94% (n = 155) of endometrial tumors and 96% (n = 242) of ovarian tumors. All breast cases (n = 241) and vulvar/cervical squamous cell carcinomas (n = 150) were negative. Among 1004 tumors from 20 sites, the only organs with positive tumors were ovary, uterus, and testis. Conclusions: SOX17 is a sensitive and specific marker for gynecologic origin in the tissues tested and may be a valuable adjunct to PAX8 and other commonly used markers to confirm endometrial or ovarian origin. SOX17 expression is lower in mucinous tumors, endocervical adenocarcinoma, high-grade neuroendocrine tumors, and undifferentiated/dedifferentiated endometrial carcinoma.

This study describes “lobular-like invasive mammary carcinomas” (LLIMCas), a group of low- to intermediate-grade invasive mammary carcinomas with discohesive, diffusely infiltrative cells showing retained circumferential membranous immunoreactivity for both E-cadherin and p120. We analyzed the clinical-pathologic features of 166 LLIMCas compared to 104 classical invasive lobular carcinomas (ILCs) and 100 grade 1 and 2 invasive ductal carcinomas (IDCs). Tumor size and pT stage of LLIMCas were intermediate between IDCs and ILCs, and yet often underestimated on imaging and showed frequent positive margins on the first resection. Despite histomorphologic similarities to classical ILC, the discohesion in LLIMCa was independent of E-cadherin/p120 immunophenotypic alteration. An exploratory, hypothesis-generating analysis of the genomic features of 14 randomly selected LLIMCas and classical ILCs (7 from each category) was performed utilizing an FDA-authorized targeted capture sequencing assay (MSK-IMPACT). None of the seven LLIMCas harbored CDH1 loss-of-function mutations, and none of the CDH1 alterations detected in two of the LLIMCas was pathogenic. In contrast, all seven ILCs harbored CDH1 loss-of-function mutations coupled with the loss of heterozygosity of the CDH1 wild-type allele. Four of the six evaluable LLIMCas were positive for CDH1 promoter methylation, which may partially explain the single-cell infiltrative morphology seen in LLIMCa. Further studies are warranted to better define the molecular basis of the discohesive cellular morphology in LLIMCa. Until more data becomes available, identifying LLIMCas and distinguishing them from typical IDCs and ILCs would be justified. In patients with LLIMCas, preoperative MRI should be entertained to guide surgical management.

Objectives: Our aim was to explore the performance of TRPS1 as an immunohistochemical diagnostic marker; find the optimal conditions for its use in breast carcinomas, especially triple-negative breast cancers (TNBCs); and compare its results in carcinomas of a select few organ sites, with an emphasis on gynecologic tumors. Methods: Tissue microarrays from breast carcinomas (n = 197), endometrial adenocarcinomas (n = 69), ovarian tumors (n = 250), vulvar squamous cell carcinomas (n = 97), pancreatic ductal adenocarcinomas (n = 20), and gastric adenocarcinomas (n = 12) were stained with TRPS1 using 2 different conditions (protocol 1: high pH; protocol 2: low pH). Breast carcinomas consisted of hormone receptor (HR)–positive/ERBB2 (formerly HER2 or HER2/neu)–negative (n = 53) samples, HR-positive/ERBB2-positive (n = 6) samples, and TNBCs (n = 138). Results: Comparing TRPS1 results in breast carcinomas vs tumors from other organ sites, the sensitivity of TRPS1 was 91% and 87%, respectively, while the specificity was 66% and 74% for protocol 1 and 2, respectively. For TNBCs vs gynecologic tumors, the sensitivity of TRPS1 was 89% and 85%, respectively, while the specificity was 65% and 73%, respectively. Conclusions: TRPS1 stains approximately 90% of breast carcinomas but also up to 71% of endometrial carcinomas, albeit with a weaker median expression. Our data show that although TRPS1 is a highly sensitive marker for TNBCs, it is not as highly specific as previously reported.

Objectives: SOX10 expression helps identify melanocytic lesions. Over time, novel uses have been identified, such as expression in triple-negative breast cancer (TNBC). We evaluated the usefulness of SOX10 in breast pathology—specifically, identification and subtyping of TNBC and distinction from gynecologic carcinomas, use as a myoepithelial marker, and in the distinction of usual ductal hyperplasia (UDH) from atypical ductal hyperplasia (ADH). Methods: Several breast and gynecologic carcinoma tissue microarrays containing a total of 492 cases were stained with SOX10. Whole sections of 34 ADH, 50 UDH, and 29 ductal carcinoma in situ (DCIS) samples were also stained with SOX10. Results: SOX10 expression was identified in 67% of consecutive TNBC cases. Expression was mostly seen in nonapocrine, androgen receptor (AR)–negative TNBCs. All gynecologic carcinomas (n = 157) were negative. All UDH cases showed mosaic SOX10 expression, while all ADH cases lacked expression. All estrogen receptor (ER)–positive DCIS (n = 19) specimens were negative for SOX10, while 2 of 10 ER-negative DCIS specimens were positive for SOX10. The latter 2 cases showed SOX10-positive invasive carcinomas. Conclusions: SOX10 identifies nonluminal AR-type TNBC and is useful in distinguishing TNBC from gynecologic carcinomas. SOX10 can distinguish UDH from ADH. SOX10 is not useful in distinguishing ADH from DCIS.

Objectives: Phyllodes tumors (PTs) are categorized by the World Health Organization (WHO) as benign, borderline, and malignant. Singapore General Hospital (SGH) nomogram is a recurrence risk assessment tool for PT, which uses cytologic atypia, mitosis, stromal overgrowth, and the surgical margin status. We studied the prognostic significance of WHO classification and its correlation to the SGH nomogram. Methods: We identified 270 consecutive cases of PT (195 benign, 49 borderline, 26 malignant). Follow-up was available on 246 cases (mean follow-up of 51 months). Results: The recurrence rates were 2% (4 of 176) for benign, 4% (2 of 46) for borderline, and 25% (6 of 24) for malignant (log-rank test P < .0001 for recurrence-free survival). Only five patients with malignant PT experienced distant recurrence. Stromal overgrowth was an independent predictor of recurrence-free survival on multivariable analysis. The mean nomogram scores for benign, borderline, and malignant PT were 20, 20.3, and 32, respectively. The higher than expected score for benign PT was due to positive margins in 39% of cases. Conclusions: The WHO three-tiered classification of PT is prognostic. Despite positive margin status, most benign PTs do not recur. Other features of the nomogram help in determining recurrence but are also used for WHO classification.