VITREOUS SEEDING OF CHOROIDAL MELANOMA.

PURPOSE: To report a case of vitreous seeding in a medium-sized choroidal melanoma and review the literature. METHODS: Observational case report and review of literature for pathogenesis, role of vitreous biopsy, and treatment outcomes. RESULTS: A case of 57-year-old man diagnosed with vitreous seeding in the left eye 1 year after episcleral brachytherapy for medium-sized choroidal melanoma. The patient was initially diagnosed to have subretinal and vitreous hemorrhage due to rupture of a retinal artery macroaneurysm for which focal laser and intravitreal antivascular endothelial growth factor injections were administered. Over the next 9 months, the vitreous hemorrhage cleared and choroidal melanoma with retinal invasion became evident. One year after brachytherapy, the primary tumor regressed with resolution of surrounding subretinal fluid and hemorrhage. However, gradual decline in the visual acuity from 20/50 to 20/500 with increase of pigmented debris over the retinal surface and in the vitreous cavity was noted. A vitreous biopsy confirmed the presence of viable melanoma cells (epithelioid type), and the eye was enucleated. Histopathology showed microscopic persistence of primary tumor with diffuse vitreous seeding. CONCLUSION: Vitreous seeding of choroidal melanoma poses a diagnostic and management challenge.

HOXA4/HOXB3 gene expression signature as a biomarker of recurrence in patients with high-grade serous ovarian cancer following primary cytoreductive surgery and first-line adjuvant chemotherapy.

OBJECTIVES: Aberrant homeobox (HOX) gene expression is reported in high-grade serous ovarian carcinoma (HGSOC), however, its prognostic significance remains unclear. METHODS: HOX genes associated with progression-free survival (PFS) in a discovery cohort of primary HGSOC samples with RNA sequencing data, and those previously reported to be associated with clinical outcomes, were selected for qPCR testing in an independent training cohort of primary HGSOC samples (n=71). A prognostic model for PFS was developed using univariate and multivariate Cox regression. Patients were stratified into risk groups that optimized the test statistic. The model was tested in an independent HGSOC cohort from The Cancer Genome Atlas (TCGA) (n=320). The effect of selected HOX genes on drug sensitivity and reactive oxygen species (ROS) accumulation was examined in vitro. RESULTS: Of 23 HOX genes tested in the training cohort, HOXA4 (HR=1.20, 95% CI=1.07-1.34, P=0.002) and HOXB3 (HR=1.09, 95% CI=1.01-1.17, P=0.027) overexpression were significantly associated with shorter PFS in multivariate analysis. Based on the optimal cutoff of the HOXA4/HOXB3 risk score, median PFS was 16.9months (95% CI=14.6-21.2months) and not reached (>80months) for patients with high and low risk scores, respectively (HR=8.89, 95% CI=2.09-37.74, P<0.001). In TCGA, the HOXA4/HOXB3 risk score was significantly associated with disease-free survival (HR=1.44, 95% CI=1.00-2.09, P=0.048). HOXA4 or HOXB3 overexpression in ovarian cancer cells decreased sensitivity to cisplatin and attenuated the generation of cisplatin-induced ROS (P<0.05). CONCLUSIONS: HOXA4/HOXB3 gene expression-based risk score may be useful for prognostic risk stratification and warrants prospective validation in HGSOC patients.

TWENTY-FIVE-GAUGE CANNULA-ASSISTED FINE-NEEDLE ASPIRATION BIOPSY OF CHOROIDAL MELANOMA: Cytopathological Analysis.

PURPOSE: To report cytopathological observations on the cells retrieved from the 25-G cannula used during prognostic transvitreal fine-needle aspiration biopsy of choroidal melanoma. METHODS: Transvitreal fine-needle aspiration biopsy of choroidal melanoma was performed through a 25-G valved cannula. Twenty samples from 20 consecutive patients were obtained. Most tumors were treated with plaque radiation therapy (16/20, 80%) following standard clinical guidelines. Four enucleated globes (4/20, 20%) were subjected to a similar transvitreal biopsy before enucleation. RESULTS: Cytopathological analysis of the cells retrieved from the cannula revealed the absence of any cells in 4 of 20 samples (20%). In the remaining 16 samples, definite melanoma cells and atypical cells (probable melanoma cells) were observed in 2 samples each (total 4, 25%). Histiocytes (4/16, 25%) and lymphocytes (1/16, 6%) were also observed. Thirteen samples (13/16, 81%) contained conjunctival epithelial epithelium. Prognostication could be performed on all fine-needle aspiration biopsy samples (20, 100%). CONCLUSION: Use of a 25-G valved cannula offers potential advantages by isolating the needle tract and by allowing retrieval of the contaminating cells without affecting the prognostic yield of the fine-needle aspiration biopsy sample.

Expression profile of COL2A1 and the pseudogene SLC6A10P predicts tumor recurrence in high-grade serous ovarian cancer.

Tumor recurrence, following initial response to adjuvant chemotherapy, is a major problem in women with high-grade serous ovarian cancer (HGSOC). Microarray analysis of primary tumors has identified genes that may be useful in risk stratification/overall survival, but are of limited value in predicting the >70% rate for tumor recurrence. In this study, we performed RNA-Seq analysis of primary and recurrent HGSOC to first identify unique differentially expressed genes. From this dataset, we selected 21 archetypical coding genes and one noncoding RNA, based on statistically significant differences in their expression profile between tumors, for validation by qPCR in a larger cohort of 110 ovarian tumors (71 primary and 39 recurrent) and for testing association of specific genes with time-to-recurrence (TTR). Kaplan-Meier tests revealed that high expression of collagen type II, alpha 1 (COL2A1) was associated with delayed TTR (HR = 0.47, 95% CI: 0.27-0.82, p = 0.008), whereas low expression of the pseudogene, solute carrier family 6 member 10 (SLC6A10P), was associated with longer TTR (HR = 0.53, 95% CI: 0.30-0.93, p = 0.027). Notably, TTR was significantly delayed for tumors that simultaneously highly expressed COL2A1 and lowly expressed SLC6A10P (HR = 0.21, 95% CI: 0.082-0.54, p = 0.0011), an estimated median of 95 months as compared to an estimated median of 16 months for subjects expressing other levels of COL2A1 and SLC6A10P. Thus, evaluating expression levels of COL2A1 and SLC6A10P at primary surgery could be beneficial for clinically managing recurrence of HGSOC.

Diagnostic Cytologic Features of Uveal Melanoma.

PURPOSE: To report the cytologic characteristics of uveal melanoma. DESIGN: This is a prospective, single-center study of consecutive patients. SUBJECTS: All patients with a clinical diagnosis of uveal melanoma from May 2009 to July 2013 who underwent prognostication fine-needle aspiration biopsy (FNAB) were included. METHODS: The cytologic characteristics of uveal melanoma were analyzed for 150 consecutive patients with a clinical diagnosis of uveal melanoma who were treated at the Cleveland Clinic Cole Eye Institute between May 2009 and August 2012. MAIN OUTCOME MEASURES: Cellular features of all cases were analyzed for cell type, presence of melanin, nuclear grade, tumor-infiltrating lymphocytes, and necrosis. Cytology was then correlated with histopathology in enucleated eyes. RESULTS: A total of 150 patients were included. Seven samples of tumor resections were excluded from the study because they were studied by impression smears. A total of 143 FNAB samples of 143 patients formed the basis for analysis. Fifty-three percent of the patients were male, and the average age for all patients was 60 years. Transcorneal (n = 8), transscleral (n = 71), and transvitreal (n = 64) approaches were used. Of 143 samples, 131 were adequate. Among these, spindle cells were observed in 98% (63% mixed and 35% spindle only), whereas only epithelioid cells were observed in 2 samples. Melanin granules were observed in 80% of samples. Tumor nuclear grade (atypia) increased with tumor height and by tumor location (least atypia with iris tumors). CONCLUSIONS: Cytologic features such as spindle cells and melanin granules, present in 98% and 80% of samples, respectively, are important cytologic diagnostic features. Tumor nuclear grade (atypia) increased with tumor height. Iris melanoma has bland features compared with ciliary and choroidal melanoma.

Implementation of tumor testing for lynch syndrome in endometrial cancers at a large academic medical center.

OBJECTIVES: Lynch syndrome (LS) is a hereditary condition that increases the risk for endometrial and other cancers. Recognizing women at risk for LS based on personal/family history is burdensome and imprecise. Tumor testing using microsatellite instability (MSI) testing and immunohistochemistry (IHC) for mismatch repair protein expression can be an effective strategy for identifying potential LS in patients presenting with colorectal or endometrial cancer. Here we describe our experience implementing a screening program for endometrial cancers. METHODS: Endometrial cancers diagnosed ≤50 years or those with suspicious personal history or histopathologic features were screened with MSI/IHC, June 2009-June 2011. Criteria were later (July 2011-July 2012) expanded to patients diagnosed <60 years, or at any age with suspicious features, and finally (after August 2012) universal screening was implemented. Screening techniques began with both MSI and IHC for every tumor, and later converted to IHC for two proteins, and MLH1 promoter methylation analysis when indicated. A genetic counselor contacted patients directly to offer genetic counseling appointments. RESULTS: Two hundred and forty-five endometrial cancers (average age, 57 years) were screened. Sixty-two patients (25%) had abnormal results, and 42 patients were referred for genetic counseling. Of the 42 patients, 34 underwent genetic counseling, 28 pursued genetic testing, and 11 were diagnosed with LS. When age and pathology criteria were used, 27 eligible cases were overlooked for screening and 3 cases of LS were found only because a clinician requested screening. CONCLUSIONS: Universal screening of endometrial cancers for LS is practical and successfully implemented with collaboration among genetic counselors, gynecologic oncologists, and pathologists.

RNA Immune Signatures from Pan-Cancer Analysis Are Prognostic for High-Grade Serous Ovarian Cancer and Other Female Cancers.

Immune cell infiltrates within the tumor microenvironment can influence treatment response and outcome in several cancers. In this study, we developed RNA-based immune signatures from pan-cancer analysis that could serve as potential markers across tumor types and tested them for association with outcome in high-grade serous ovarian cancer (HGSOC) and other female cancers. Pan-cancer RNA-Seq cluster analysis of immune-related gene expression profiles in The Cancer Genome Atlas (TCGA) from 29 different solid tumors (4446 specimens) identified distinct but concordant gene signatures. Among these immune signatures, Cytotoxic Lymphocyte Immune Signature (CLIS), T-cell trafficking (TCT), and the TCT to M2 tumor-associated macrophage (M2TAM) ratio (TCT:M2TAM) were significantly (p < 0.05) associated with overall survival (OS), using multivariable Cox proportional hazards regression models, in a discovery cohort and two independent validation cohorts of HGSOC patients. Notably, the TCT:M2TAM ratio was highly significant (p ≤ 0.000001) in two HGSOC cohorts. Immune signatures were also significant (p < 0.05) in the presence of tumor cytoreduction, BRCA1/2 mutation, and COL2A1 expression. Importantly, the CLIS and TCT signatures were also validated for prognostic significance (p < 0.05) in TCGA cohorts for endometrial and high tumor mutational burden (Hi-TMB) breast cancer. These immune signatures also have the potential for being predictive in other cancers and for patients following different treatment strategies.

Significance of atypical endometrial cells in women younger than 40 years of age.

INTRODUCTION: The presence of atypical endometrial cells in the Papanicolaou (Pap) test has been associated with an increased rate of endometrial malignancy, with reported rates ranging from 14% to 47%. However, most reported studies have focused on patients who were aged >40 years. The purpose of the present study was to investigate the clinical significance of identifying atypical endometrial cells in Pap test samples in women aged <40 years of age. MATERIALS AND METHODS: A search of the cytology Pap test database was performed from 2000 to 2014 using the keywords "atypical endometrial cells" or "atypical glandular cells favor endometrial origin" in women aged <40 years. The available ThinPrep slides were reviewed. The patients' clinical presentation, follow-up endometrial biopsy findings, treatment, and clinical follow-up data were recorded. Endometrial carcinoma tissue sections were screened for Lynch syndrome. RESULTS: The database search yielded 63 study cases. Of these 63 patients, 52 had subsequently undergone endometrial biopsy. Of the 52 patients with follow-up biopsy findings available, 9 (17.3%) had premalignant (5 with atypical hyperplasia) or malignant (4 with endometrioid adenocarcinoma) lesions. In addition, 16 patients (30.8%) had other endometrial pathologic features. The 9 patients with premalignant or malignant endometrial lesions (8 white, 1 black) were overweight or obese; 3 of the patients did not have any clinical symptoms. All 4 patients with endometrioid adenocarcinoma had negative Lynch syndrome screening findings. CONCLUSIONS: Our results suggest that it is important to recognize the presence of atypical endometrial cells in the Pap tests from young patients, given its association with the finding of premalignant and malignant pathologic features in subsequent endometrial biopsies.

Pelvic endometriosis is rarely associated with ovarian borderline tumours, cytologic and architectural atypia: a clinicopathologic study.

Endometriotic foci, especially ovarian ones, with epithelial cytologic atypia may be precursors of cancer. This study presents an overview of the atypical cytological and histopathological findings associated with endometriosis. Six cases of endometriosis, with atypical histological and cytological changes, were obtained from the archives of the Department of Pathology at Cleveland Clinic Foundation between year 2000 and 2003. The size of the base from which these cases were drawn was 2000 cases of endometriosis. The age range of the patients was from 29 to 52 years. The clinical presentations included infertility (three cases), pelvic pain (three cases), adenexal and pelvic masses (four cases). Stage IV endometriosis with extensive pelvic involvement was found in two patients. Intraoperatively, the endometriotic lesions involved the ovaries (all cases); Cul de sac (four cases); urinary bladder (two cases); sigmoid colon, hemidiaphragms, and uterine vessels (one case each). The endometriotic lesions were associated with uterine leiomyomas (two patients) and adenocarcinoma of the vagina (one patient). Histologically, in addition to endometrial type glands and stroma, usually found in endometriosis, we observed both cytologic and pattern atypism involving the epithelium in all cases. The features of cytologic atypia included nuclear stratification, hyperchromatism, and pleomorphism. The features of pattern atypia were complex glandular pattern, papillary formations and psammoma bodies. In two cases, these features were sufficient for diagnosis of borderline Mullerian seromucinous tumours. One patient had recurred with metastatic adenocarcinoma of the vault. She died later from disseminated metastatic disease. There is a rare association between pelvic endometriosis and borderline ovarian tumours (three cases), cytologic and pattern atypia (two cases); mesothelial hyperplasia, endosalpingiosis (two cases), and metastasis (one case). Cytologic and pattern atypia can develop in the endometriotic foci and therefore, these lesions should be thoroughly scrutinized for presence of these changes. Our findings recommend surgical excision of these foci rather than their simple cauterization.

Fine-needle aspiration biopsy for suspected uveal metastases.

OBJECTIVE: One indication of fine-needle aspiration biopsy (FNAB) is the diagnostic confirmatory of a clinical suspicion of uveal metastasis. We analyzed our experience in this clinical setting to assess the effectiveness of FNAB technique. DESIGN: Retrospective study. PARTICIPANTS: 28 patients (28 eyes) underwent FNAB biopsy. METHODS: Aspirates were performed using 25-gauge needle and were classified into the following categories: positive, atypical, negative, or nondiagnostic. The electronic medical records provided all clinical data. Subsequent clinical course was considered as the diagnostic standard. RESULTS: Subsequent clinical course was metastatic tumour in 19 cases (68%) and nonmetastatic tumour in other 9 cases, considered as the diagnostic standard. Cytological interpretations for metastases were positive in 19 cases (68%), atypical in 2 cases (7%), negative in 4 cases (14%), and nondiagnostic in 3 cases (11%). The metastasis-positive cases included 9 adenocarcinoma, 3 uveal lymphoma, 3 small cell carcinomas, 3 non-small cell carcinomas, and 1 metastatic paraganglioma. Both of the atypical cases were suggestive for non-Hodgkin lymphoma. The 4 negative cases for metastases included 2 true negative cases, and 2 false negative aspirates that subsequently proved to be metastatic adenocarcinoma. The 3 nondiagnostic cases included 1 schwannoma, 1 low-grade uveal non-Hodgkin lymphoma, and 1 metastatic adenocarcinoma. The overall sensitivity for FNAB was 87.5%, with a specificity of 100%. CONCLUSIONS: FNAB of suspected uveal metastases is a reliable diagnostic technique.

Multifocal Primary Uveal Melanoma: Clinical and Molecular Characteristics.

We report two patients who developed a second distinct choroidal melanoma in the same eye following successful regression of their first choroidal melanoma after iodine-125 plaque brachytherapy. Neither patient demonstrated ocular melanocytosis, local tumor recurrence, or vitreous seeding. One patient had the second tumor arising from a previously documented choroidal nevus, and after undergoing enucleation, there was no detectable connection between the tumors on histopathologic examination. Germline BAP1 mutation was absent in both cases. Multifocal primary uveal melanoma is a rare entity in which the second tumor may occur either de novo or from a malignant transformation of a choroidal nevus. Known risk factors include ocular melanocytosis or germline BAP1 mutation. Additional underlying mechanisms have yet to be elucidated.

Predicting success of endoscopic aspiration for suspected pancreatic cystic neoplasms.

CONTEXT: Analysis of pancreatic cyst fluid can play a role in the management of asymptomatic cystic neoplasms. OBJECTIVE: Our aim was to determine whether cyst size or location can predict the success of cyst fluid collection and analysis. DESIGN: Review of prospective management protocol. SETTING: Tertiary care referral center. PATIENTS: Three-hundreds and 70 patients with suspected pancreatic cystic neoplasms evaluated over 6 years. INTERVENTIONS: Endoscopic ultrasound aspiration for up to 3 variables: cytology including extracellular mucin, CEA, and amylase. MAIN OUTCOME MEASURES: The number of variables obtained were compared with cyst size and location. RESULTS: The distribution of unilocular cystic lesions was: 125 (33.8%) head, 105 (28.4%) tail, 77 (20.8%) body, 37 (10.0%) uncinate and 13 (3.5%) multiple cysts. In addition, 13 (3.5%) patients had uncertain cyst location. There was no association between cyst location and number of variables obtained (P=0.148). An aspirate was obtained in 284 patients (76.8%) with a mean volume of 8.3 mL. There was a significant correlation between cyst size and volume aspirated (P<0.001). The number of variables obtained was significantly correlated with cyst size (P<0.001): 3 variables were obtained in 109 out of 284 (38.4%) with a median size of 3.0 cm. Logistic regression curves predict likelihood of success based on cyst size. An unsuccessful attempt at EUS aspiration for cysts occurred in 31 of the 284 cases (10.9%) with a median size of 1.5 cm. CONCLUSIONS: Successful endoscopic ultrasound aspiration of pancreatic cysts is independent of cyst location, but correlates with size, which can be useful in deciding which patients should undergo endoscopic ultrasound and aspiration.

Reflex UroVysion testing of bladder cancer surveillance patients with equivocal or negative urine cytology: a prospective study with focus on the natural history of anticipatory positive findings.

A proportion of patients under surveillance for recurrent bladder carcinoma with no immediate evidence of bladder tumor recurrence have positive multitarget fluorescence in situ hybridization (FISH; UroVysion, Vysis, Downers Grove, IL) results. The course of these "anticipatory positive" cases and the time to bladder tumor recurrence remains unknown. We followed up 250 patients with urine cytologic results, concurrent multitarget FISH, and cystoscopic examination for recurrent urothelial carcinoma. Of 81 cases (32.4%) with FISH-positive results, tumor recurrence developed in 60 (74.0%). Of 169 (67.6%) FISH-negative cases, recurrent urothelial carcinoma developed in 22 (13.0%). Of 211 patients (84.4%) with negative cystoscopic examination results, 56 (26.5%) had positive FISH results, and in 35 (62.5%) of these patients, recurrent urothelial carcinoma developed. Approximately 27% of patients under bladder carcinoma surveillance without immediate evidence of tumor recurrence will have a positive FISH result, defining the anticipatory positive subset. In about 65% of this anticipatory positive group, recurrent bladder urothelial carcinoma developed within 29 months.

A Pigmented Iris Lesion.

A patient in their mid-60s presented with a left iris pigmented lesion that had been present for decades and remained stable in size. What would you do next?

Reactive Retinal Astrocytic Tumor (Focal Nodular Gliosis): Report of the Clinical Spectrum of 3 Cases.

PURPOSE: To report 3 cases providing insight into clinical progression of reactive retinal astrocytic tumor. METHODS: The clinical, imaging, and when available, the cytologic features of 3 cases of reactive retinal astrocytic tumor (focal nodular gliosis) were reviewed. RESULTS: A 6-year-old female, a 49-year-old man, and a 39-year-old man each developed a white retinal mass associated with laser photocoagulation, lattice degeneration, and treatment of a presumed vascular tumor, respectively. All tumors were white, circumscribed retinal masses that tended to be associated with exudation and either initially or eventually minimal vascularity. CONCLUSION: Reactive retinal astrocytic tumor can be observed in response to a degenerative, inflammatory, or ischemic retinal insult. Such tumors may progress after therapeutic intervention.

Versican Proteolysis by ADAMTS Proteases and Its Influence on Sex Steroid Receptor Expression in Uterine Leiomyoma.

Context: Leiomyomas have abundant extracellular matrix (ECM), with upregulation of versican, a large proteoglycan. Objective: We investigated ADAMTS (a disintegrin-like and metalloprotease with thrombospondin type 1 motifs) protease-mediated versican cleavage in myometrium and leiomyoma and the effect of versican knockdown in leiomyoma cells. Design: We used quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blotting, immunohistochemistry, and RNA in situ hybridization for analysis of myometrium, leiomyoma and immortalized myometrium and leiomyoma cells. Short interfering RNA (siRNA) was used to knockdown versican in leiomyoma cells. Setting: This study was performed in an academic laboratory. Patients: Study subjects were women with symptomatic or asymptomatic leiomyoma. Main Outcome Measures: We quantified messenger RNAs (mRNAs) for versican splice variants. We identified ADAMTS-cleaved versican in myometrium and leiomyoma and ADAMTS messenger RNAs and examined the effect of VCAN siRNA on smooth muscle differentiation and expression of estrogen and progesterone receptors. Results: The women in the symptomatic group (n = 7) had larger leiomyoma (P = 0.01), heavy menstrual bleeding (P < 0.01), and lower hemoglobin levels (P = 0.02) compared with the asymptomatic group (n = 7), but were similar in age and menopausal status. Versican V0 and V1 isoforms were upregulated in the leiomyomas of symptomatic versus asymptomatic women (P = 0.03 and P = 0.04, respectively). Abundant cleaved versican was detected in leiomyoma and myometrium, as well as in myometrial and leiomyoma cell lines. ADAMTS4 (P = 0.03) and ADAMTS15 (P = 0.04) were upregulated in symptomatic leiomyomas. VCAN siRNA did not effect cell proliferation, apoptosis, or smooth muscle markers, but reduced ESR1 and PR-A expression (P = 0.001 and P = 0.002, respectively). Conclusions: Versican in myometrium, leiomyomas and in the corresponding immortalized cells is cleaved by ADAMTS proteases. VCAN siRNA suppresses production of estrogen receptor 1 and progesterone receptor-A. These findings have implications for leiomyoma growth.

Limbal Stem Cell Preservation During Proton Beam Irradiation for Diffuse Iris Melanoma.

PURPOSE: To report the outcome after limbal stem cell preservation during proton beam irradiation for diffuse iris melanoma. METHODS: This is a single-case report of diffuse iris melanoma that was managed with proton beam radiation (53 Gy), wherein preemptively harvested superior and inferior limbal stem cells before radiation were replaced after irradiation. Regeneration of the palisades of Vogt and the limbal stem cells was documented by an optical coherence tomography-based imaging protocol. RESULTS: At 24 months after radiation therapy, best-corrected visual acuity was 20/25. The cornea was clear without evidence of limbal stem cell dysfunction. Clinical examination (including gonioscopy and ultrasound biomicroscopy [UBM]) was indicative of local control, and systemic surveillance was negative for metastatic disease. At posttransplant (21 months), there were more palisade structures visible in both anterior and posterior regions of the superior and inferior limbus, and the linear presentation of the inferior palisades appears to have regenerated. CONCLUSIONS: Diffuse iris melanoma can be managed successfully with proton beam radiation while preserving corneal limbal stem cells by harvesting them before radiation and then replacing them after irradiation. Regeneration of the palisades of Vogt could be documented by an optical coherence tomography-based imaging protocol.

Endosalpingiosis of Axillary Lymph Nodes: A Rare Histopathologic Pitfall with Clinical Relevance for Breast Cancer Staging.

Establishment of accurate axillary lymph node status is of essential importance in determining both prognosis and the potential need for adjuvant therapy in patients with invasive breast cancer. Axillary lymph node heterotopias can in some cases result in overdiagnosis of metastatic disease. Nodal endosalpingiosis is perhaps the least commonly reported type of axially lymph node heterotopia. We herein illustrate a case in which second opinion pathologic interpretation combined with ancillary immunohistochemical studies allowed for a specific diagnosis of axillary nodal müllerian-type inclusions, confirming ypN0 staging and resulting in appropriate disease management and prognostication.