Phoebe Meredith Hammer

All Publications

• Perivascular Epithelioid Cell-Family Tumors in Children, Adolescents and Young Adults:Clinicopathologic Features in 70 Cases. Archives of pathology & laboratory medicine Hammer, P. M., Toland, A., Shaheen, M., Shenoy, A., Esnakula, A., Hicks, M. J., Warran, M., Al-Ibraheemi, A., Davis, J. L., Tan, S. Y. 2024

  Abstract

  Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors of uncertain histogenesis expressing smooth muscle and melanocytic markers. The clinicopathologic spectrum in young patients is not well documented.To describe a multi-institutional series of PEComas in children, adolescents, and young adults.PEComas, not otherwise specified (NOS); angiomyolipomas (AMLs); lymphangioleiomyomatosis; and clear cell sugar tumors were retrospectively identified from 6 institutions and authors' files.Seventy PEComas in 64 patients (median age, 15 years) were identified. They were more common in females (45 of 64 patients), occurring predominately in kidney (53 of 70), followed by liver (6 of 70). Thirty-four patients had confirmed tuberous sclerosis complex (TSC), 3 suspected TSC mosaicism, 2 Li-Fraumeni syndrome (LFS) and 1 neurofibromatosis type 1. Most common variants were classic (49 of 70) and epithelioid (8 of 70) AML. Among patients with AMLs, most (34 of 47) had TSC, and more TSC patients had multiple AMLs (15 of 36) than non-TSC patients (2 of 13). Two TSC patients developed malignant transformation of classic AMLs: 1 angiosarcomatous and 1 malignant epithelioid. Lymphangioleiomyomatosis (5 of 70) occurred in females only, usually in the TSC context (4 of 5). PEComas-NOS (6 of 70) occurred exclusively in non-TSC patients, 2 of whom had LFS (2 of 6). Three were malignant, 1 had uncertain malignant potential, and 2 were benign. All 4 PEComas-NOS in non-LFS patients had TFE3 rearrangements.Compared to the general population, TSC was more prevalent in our cohort; PEComas-NOS showed more frequent TFE3 rearrangements and possible association with LFS. This series expands the spectrum of PEComas in young patients and demonstrates molecular features and germline contexts that set them apart from older patients.

  View details for DOI 10.5858/arpa.2023-0552-OA

  View details for PubMedID 38547914

• Soft Tissue Perivascular Epithelioid Cell Tumors. Surgical pathology clinics Hammer, P. M., Tan, S. Y. 2024; 17 (1): 105-118

  Abstract

  Perivascular epithelioid cell tumors (PEComas) are a heterogenous group of mesenchymal neoplasms with a mixed myomelanocytic immunophenotype. PEComa-family tumors include angiomyolipoma, lymphangioleiomyomatosis, and a large category of rare neoplasms throughout the body that are now classified under the umbrella term "PEComa." This review focuses on recent advances in the clinicopathological and molecular features of PEComas, with an emphasis on PEComas that originate in soft tissue.

  View details for DOI 10.1016/j.path.2023.06.002

  View details for PubMedID 38278600

• Does lymph node assessment change the prognostic significance of substantial LVSI and p53 status in endometrial endometrioid carcinoma? Gynecologic oncology Hui, C., Mendoza, M. G., von Eyben, R., Dorigo, O., Litkouhi, B., Renz, M., Karam, A., Hammer, P. M., Howitt, B. E., Kidd, E. 2023; 177: 150-156

  Abstract

  The PORTEC-2 update suggested that substantial lymphovascular space invasion (LVSI) and abnormal p53 expression (p53abnl) predict for poorer outcomes and that these patients should be treated with external beam radiation therapy (EBRT). We aim to determine if patients with these risk factors who undergo a lymph node (LN) assessment show similar outcomes.We retrospectively reviewed 126 patients with FIGO 2009 stage IA grade 3, stage IB grade 1-2, and stage IIIC (positive LN but no other stage II/III risk factors) endometrioid endometrial cancer who underwent LN assessment. Local (LR), regional recurrences (RR), and distant metastases were analyzed using competing risk methods, and overall survival (OS) was analyzed using Kaplan-Meier.Median follow-up time was 37.2 months. OS was significantly different between patients with and without p53abnl expression (16.7% versus 3.1% deceased), and between patients with and without LVSI (11.1% versus 1.5% deceased; p < 0.01 for both). The 2-year cumulative incidence of LR for patients with p53abnl versus wild type p53 and LVSI versus no LVSI was 11.1% (95% CI 0-25.6) versus 2.2% (95% CI 0-5.25; p = 0.04), and 11.4% (95% CI 2.0-20.9) versus 0%, respectively (p < 0.01). The 2-year cumulative RR in patients with LVSI versus no LVSI was 6.9% (95% CI 0-14.4) versus 0% (p = 0.05). No patients who completed pelvic RT experienced an in-field recurrence.Despite LN assessment, patients with high-intermediate risk early-stage or stage IIIC (with positive lymph nodes only but no other stage II or III risk factors) endometrial cancer with p53abnl expression and/or LVSI have worse outcomes. These patients may derive benefit from intensification with EBRT to improve local and pelvic control.

  View details for DOI 10.1016/j.ygyno.2023.09.001

  View details for PubMedID 37696217

• Detection of FOXL2 C134W Mutation Status by a Novel BaseScope-ISH Assay is Highly Sensitive and Specific for Adult Granulosa Cell Tumors. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc Hammer, P. M., Wang, A., Beard, C., Zdravkovic, S., Tenney, T., Liang, B., Das, I., Bremer, R., Wang, L. C., McCluggage, W. G., Stewart, C. J., Howitt, B. E. 2023: 100318

  Abstract

  Adult granulosa cell tumors (AGCT) are a molecularly distinct group of malignant ovarian sex cord-stromal tumors (SCST) characterized by a nearly ubiquitous c.402C>G/p.C134W mutation in FOXL2 (hereafter referred to as "C134W"). In some cases, AGCT exhibits marked morphological overlap with other SCSTs, and have an identical immunophenotype, and molecular testing may be necessary to help confirm the diagnosis. However, molecular testing is time-consuming, relatively expensive, and unavailable in many pathology laboratories. We describe the development and validation of an in situ hybridization (ISH) custom BaseScope assay for the detection of the FOXL2 C134W mutation. We evaluated 106 ovarian SCSTs, including 78 AGCT, 9 juvenile granulosa cell tumors, 18 fibromas (cellular and conventional), and 1 SCST, not otherwise specified (NOS), as well as 53 epithelial ovarian tumors (42 endometrioid carcinomas and 11 carcinosarcomas) and 1 STK11 adnexal tumor for the presence or absence of FOXL2 wild-type and FOXL2 C134W RNA expression via Basescope-ISH. Fifty-one tumors had previously undergone DNA sequencing of the FOXL2 gene. Across the entire cohort, the FOXL2 C134W probe staining was positive in 77/78 (98.7%) AGCTs. 2/81 (2.5%) non-AGCT also showed positive staining, both of which were epithelial ovarian tumors. The assay worked in tissue blocks >20 years old. There was 100% concordance between the FOXL2 sequencing and Basescope-ISH results. Overall, assessment of FOXL2 mutation status by custom Basescope-ISH demonstrated 98.7% sensitivity and 97.5% specificity for the diagnosis of AGCT. Basescope-ISH for FOXL2 C134W represents a reasonable alternative to sequencing, is quicker and less expensive, and is more easily incorporated than molecular testing into many pathology laboratories. It also has the advantage of requiring less tissue, and the neoplastic cells can be directly visualized on stained sections.

  View details for DOI 10.1016/j.modpat.2023.100318

  View details for PubMedID 37634867

• Polarization of Endothelial and Epithelial Cell States Predicts Recurrence in Endometrial Endometrioid Carcinoma Nief, C., Hammer, P., Wang, A., Gentles, A., Howitt, B. ELSEVIER SCIENCE INC. 2023: S962-S963

  View details for Web of Science ID 000990969802103

• TCGA Molecular Subgroup Shows Greater Prognostic Significance Than Histologic Diagnosis in High-Grade Endometrial Carcinomas with Spindled, Undifferentiated and Sarcomatous Components Hammer, P., Wang, A., Zdravkovic, S., Heilbroner, L., Ryan, E., Mills, A., Jenkins, T., Howitt, B. ELSEVIER SCIENCE INC. 2023: S913-S914

  View details for Web of Science ID 000990969802055

• A Subset of SMARCB1 (INI-1) Deficient Vulvar Neoplasms Express Germ Cell Markers. Histopathology Hammer, P. M., Kolin, D. L., Charville, G. W., McCluggage, W. G., Howitt, B. E. 2022

  Abstract

  SMARCB1 (INI-1) deficient vulvar neoplasms comprise a group of rare tumors that include epithelioid sarcoma (ES), myoepithelial carcinoma (MEC), the recently described myoepithelioma-like tumor of the vulvar region (MELTVR), and sarcomas which are difficult to classify. It has been suggested that so-called vulvar yolk sac tumors (YST) may represent morphologic variants of SMARCB1-deficient tumors; thus we investigated the immunoreactivity of germ cell markers in SMARCB1-deficient vulvar neoplasms.Ten SMARCB1-deficient vulvar neoplasms were stained with germ cell tumor markers (SALL4, glypican-3, OCT3/4, and AFP) and re-reviewed for morphologic features. The tumors occurred in adult females (median age 41 years) and included ES (n=7), MELTVR (n=2), and MEC (n=1). All cases showed loss of SMARCB1 expression. Four cases (40%) were focally positive for SALL4 in areas with morphology of typical-appearing ES. One of these cases also showed focal staining for OCT3/4. One ES showed a transition from typical-appearing ES to YST-like morphology, with diffuse expression of SALL4 and glypican-3, and focal expression of AFP, in these latter areas. All other tested cases were negative for AFP.Our study reveals that SALL4, glypican-3, and OCT3/4 are positive in a subset of SMARCB1-deficient vulvar neoplasms, which may pose a diagnostic challenge and result in consideration of a germ cell tumor. We also highlight a case with transition from ES to YST-like morphology, lending further support that YSTs of the vulva are somatically derived SMARCB1-deficient neoplasms and do not represent true germ-cell neoplasia.

  View details for DOI 10.1111/his.14709

  View details for PubMedID 35758187

• A Subset of SMARCB1 (INI-1) Deficient Vulvar Neoplasms are Positive for Germ Cell Markers Hammer, P., McCluggage, W., Kolin, D., Howitt, B. SPRINGERNATURE. 2022: 755-756

  View details for Web of Science ID 000770360202043

• A Subset of SMARCB1 (INI-1) Deficient Vulvar Neoplasms are Positive for Germ Cell Markers Hammer, P., McCluggage, W., Kolin, D., Howitt, B. SPRINGERNATURE. 2022: 755-756

  View details for Web of Science ID 000770361802043

• Intravascular adenomyomatosis: a morphologic variant of intravenous leiomyomatosis associated with endometriosis and potential for misdiagnosis. Human pathology Fitzpatrick, M. B., Hammer, P. M., Yang, E. J., Howitt, B. E. 2021

  Abstract

  Intravenous leiomyomatosis (IVL) is a quasi-malignant smooth muscle tumor involving lymphatic and venous spaces of the myometrium. Rare cases of IVL with admixed endometrial glands and stroma have been described, termed intravascular adenomyomatosis. We report four additional cases of intravascular adenomyomatosis and expand the clinicopathologic features of these rare tumors. Patients were 39-45 years old and presented with symptoms of dysmenorrhea, postmenopausal bleeding, or pelvic mass. All cases were associated with endometriosis. Three cases comprised intravascular bland smooth muscle tumors with plexiform features, and in some foci the intravascular tumor contained endometrial type glands and stroma. In one case there was extensive (>10) foci of intravascular adenomyomatosis without evidence of associated smooth muscle neoplasm but did have an endometrial polyp with adenomyomatous features. None of the cases had nuclear atypia, increased mitotic activity, or tumor cell necrosis. The endometrial stromal components were positive for CD10 and negative or weakly positive for desmin by immunohistochemistry. Two cases underwent molecular testing for JAZF1 and PHF1 rearrangements with negative results. Three patients had no evidence of disease at the time of last follow-up, and one had persistent but stable disease 7 years after incomplete surgical removal and megestrol acetate treatment. Intravascular adenomyomatosis is a variant morphology rarely seen in IVL that lacks characteristic morphologic and molecular features of endometrial stromal sarcoma. Like IVL, prognosis is likely linked to completeness of surgical resection. In this study we found that intravascular adenomyomatosis is frequently associated with endometriosis, a novel finding to add to the literature on this rare IVL variant.

  View details for DOI 10.1016/j.humpath.2021.11.009

  View details for PubMedID 34856302

• Black and Blue: Eyes and Dyes Sobel, R., Nirschl, J., Hammer, P., Sanchez, R., Pershing, S., Louie, C., Lin, J. OXFORD UNIV PRESS INC. 2021: 579

  View details for Web of Science ID 000671021700089

• Molecular Classification of Endometrial Carcinomas with Long-Term Follow-up Hammer, P., Albro, J., Squires, C., Peters-Schulze, G., Sharp, B., Charu, V., Cessna, M., Howitt, B. SPRINGERNATURE. 2021: 691–93

  View details for Web of Science ID 000629690900575

• 100 Years of the Pathology Medical Student Fellowship: Impacts on Undergraduate Education and Career Choices Hammer, P., Ireland, K., Houghton, D., Jaggers, A., Coleman, A., Snir, O., Troxell, M., Andeen, N. SPRINGERNATURE. 2021: 332–33

  View details for Web of Science ID 000629694100282

• Well-differentiated lipomatous neoplasms with p53 alterations: A clinicopathologic and molecular study of eight cases with features of atypical pleomorphic lipomatous tumor. Histopathology Hammer, P. M., Kunder, C. A., Howitt, B. E., Charville, G. W. 2021

  Abstract

  Well-differentiated lipomatous neoplasms encompass a broad spectrum of benign and malignant tumors, many of which are characterized by recurrent genetic abnormalities. Although a key regulator of p53 signaling, MDM2, is characteristically amplified in well-differentiated liposarcoma, recurrent abnormalities of p53 itself have not been reported in well-differentiated adipocytic neoplasms. Here, we present a series of well-differentiated lipomatous tumors characterized by p53 alterations and histologic features in keeping with atypical pleomorphic lipomatous tumor (APLT).We reviewed the morphologic, immunohistochemical, and molecular genetic features of eight lipomatous tumors with p53 alterations. Four tumors arose in the thigh, and one case each arose in the shoulder, calf, upper back, and subclavicular regions; six tumors were deep/subfascial and two were subcutaneous. Relevant clinical history included two patients with Li-Fraumeni syndrome. Morphologically, all cases demonstrated well-differentiated adipocytes with prominent nuclear pleomorphism, limited mitotic activity, and no tumor cell necrosis. All cases were negative for MDM2 overexpression and amplification by immunohistochemistry and fluorescence in situ hybridization, respectively. By immunohistochemistry, p16 was diffusely overexpressed in all cases; seven tumors (88%) showed abnormal loss of Rb and p53. TP53 mutation or deletion was identified in 4 of 6 tumors evaluated by exon-targeted hybrid capture-based massively parallel sequencing; RB1 mutation or deletion was present in 5 of 6 cases.We present a series of eight well-differentiated lipomatous neoplasms characterized by p53 alterations in addition to Rb loss and histologic features of APLT. These findings suggest that impaired p53 signaling may contribute to the pathogenesis of APLT in a subset of cases.

  View details for DOI 10.1111/his.14593

  View details for PubMedID 34725851

• One Hundred Years of the Pathology Medical Student Fellowship. Archives of pathology & laboratory medicine Hammer, P., Ireland, K., Houghton, D. C., Jaggers, A., Coleman, A., Snir, O. L., Troxell, M. L., Andeen, N. K. 2021

  Abstract

  The Pathology Medical Student Fellowship (PSF) is a unique, year-long immersive educational experience. Review of institutional archives describes a medical student "Fellowship in Pathology" founded in 1919.To characterize the impacts of this 100-year-old program.We determined subsequent medical specialty of each PSF graduate in our department and surveyed those with available contact information.Of 145 pathology student fellows graduating between 1924 and 2020, a total of 50 (34.4%) matched into pathology; medical, surgical, and radiology subspecialties were also well-represented career choices. Between 2001 and 2020, of 36 students who matched into pathology from our institution, 19 (52.8%) had completed the fellowship. Survey respondents (n = 42) indicated that before the PSF, 11 of 42 students (26.2 %) were undecided in specialty, with only 6 (14.3%) identifying pathology as their primary field of interest. Of survey respondents who had completed training, 26 (61.9%) practice in academic settings. Nonpathology physicians reported frequent utilization of skills gained during the PSF year, with 5 of 23 (21.7%) responding "daily," and 9 (39.1%) responding "weekly." The most useful skills included knowledge of pathophysiology of disease and anatomy, improved communication with multidisciplinary teams, and/or interpretation of pathology results (each selected by 17 to 20 students, 73.9%-87.0%). Free-text responses on impacts of the PSF described enhanced knowledge of disease pathobiology and diagnostic complexity and increased confidence and autonomy.We describe the program structure, educational benefits, graduate specialty choices, and career impacts of 100 years of the PSF at our institution. Although undecided before pathology exposure, many PSF graduates subsequently enter pathology careers. Regardless of specialty choice, PSF graduates have a high rate of subsequently pursuing academic medical careers.

  View details for DOI 10.5858/arpa.2021-0220-OA

  View details for PubMedID 34784414

• Differential Diagnosis of a Unique Vulvar Mass in an Adolescent. Obstetrics and gynecology Chow, S., Doyle, A., Hammer, P., Tyson, N. A. 2021

  Abstract

  Vulvar masses in adolescents have a broad differential diagnosis, yet few reports exist detailing masses of mammary origin.A nulliparous, healthy 16-year-old adolescent presented with a longstanding, ulcerated, 17-cm vulvar mass of unknown origin and pronounced inguinal lymphadenopathy. The patient underwent a left radical partial vulvectomy, with pathology revealing terminal duct lobular units consistent with polymastia.Differential diagnosis of a vulvar mass in an adolescent should include polymastia.

  View details for DOI 10.1097/AOG.0000000000004563

  View details for PubMedID 34735404

• The utility and challenges of histopathologic evaluation in the diagnosis of nonmalignant skin ulcers. Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society Hammer, P., Latour, E., Bohnett, M. C., McKenzie, F., Korcheva, V. B., Mengden, S., White, K. P., Ortega-Loayza, A. G. 2020; 28 (2): 219-223

  Abstract

  Histopathologic evaluation of cutaneous ulcers is indicated when the clinical diagnosis is unclear or when ulcers have not responded to standard of care. Many nonmalignant skin ulcers lack specific histologic findings on biopsy and pose a diagnostic challenge. While the usefulness of skin biopsies to diagnose underlying malignancy in ulcerated lesions has been demonstrated in previous studies, their utility in the diagnosis of ulcers of other etiologies has not been reported. We conducted a retrospective study of 45 nonmalignant ulcer biopsies in a 3-year period to compare the histologic diagnosis with the final diagnosis. Additionally, we assessed the diagnostic concordance among three blinded dermatopathologists when reviewing these cases. The leading histologic diagnosis from each of the three observers agreed with the final clinical diagnosis, on average, for 29.6% of the cases (average pairwise kappa = 0.15). Inflammatory ulcers had the lowest concordance between the observers and final diagnosis with an average of 26.0% of cases (average pairwise kappa = 0.06). The observers agreed with each other for 35.6% of the cases (Fleiss' kappa = 0.32). The highest agreement among observers was in the vascular/vasculopathic category (50%, Fleiss' kappa = 0.44). Our results indicate that skin biopsies alone are useful in the evaluation of nonmalignant ulcers to rule out other conditions (e.g. neoplasm) but frequently not sufficient to establish a definitive diagnosis. Additional clinicopathologic correlation is necessary in the final assessment of nonmalignant ulcers to determine the diagnosis. Future research endeavors should explore alternative approaches to more efficiently diagnose nonmalignant skin ulcers.

  View details for DOI 10.1111/wrr.12780

  View details for PubMedID 31705777

• Characterisation and diagnosis of ulcers in inpatient dermatology consultation services: A multi-centre study. International wound journal Haynes, D., Hammer, P., Malachowski, S. J., Kaffenberger, B., Yi, J. S., Vera, N., Calhoun, C., Shinohara, M. M., Seminario-Vidal, L., Trinidad, J. C., Keller, J. J., Ortega-Loayza, A. G. 2019; 16 (6): 1440-1444

  Abstract

  Accurate and prompt diagnosis of skin ulcers is critical to optimise management; however, studies in hospitalised patients are limited. This retrospective review of dermatologic consultations included 272 inpatients with skin ulcers between July 2015 and July 2018 in four U.S. academic hospitals. The median age was 54 years and 45% were male. In 49.3% of the patients, skin ulcers were considered the primary reason for admission. Ulcers of 62% were chronic and 49.6% were located on the lower extremities. Pyoderma gangrenosum (17.3%), infection (12.5%), and exogenous causes (11.8%) were the leading aetiologies; 12% remained diagnostically inconclusive after consultation. Diagnostic agreements pre-dermatology and post-dermatology consult ranged from 0.104 (n = 77, 95% CI 0.051-0.194) to 0.553 (n = 76, 95% CI 0.440-0.659), indicating poor-modest agreement. This study highlights the diagnostic complexity and relative incidences of skin ulcers in the inpatient setting.

  View details for DOI 10.1111/iwj.13211

  View details for PubMedID 31475449

• Nipple leiomyoma: A rare neoplasm with a broad spectrum of histologic appearances. Journal of cutaneous pathology Hammer, P., White, K., Mengden, S., Korcheva, V., Raess, P. W. 2019; 46 (5): 343-346

  Abstract

  Cutaneous leiomyomas are rare benign smooth-muscle tumors. These lesions are distinguished based on their cell of origin and are subclassified as pilar leiomyoma, angioleiomyoma, and genital-type leiomyoma. Nipple leiomyoma is the least common genital-type leiomyoma, arising from the dartoic muscle cell of the nipple. Histologic examination of the lesion is necessary for definitive diagnosis, and these uncommon tumors can pose a diagnostic challenge. We describe herein a series of six nipple leiomyomas with a spectrum of histologic appearances.

  View details for DOI 10.1111/cup.13423

  View details for PubMedID 30663114