1.Concordance between the Ki-67 and proliferation index of molecular signature tests (MammaPrint and OncotypeDX) among Filipino patients in two St. Luke’s Medical Center facilities: An analytical cross-sectional study.
Rebecca NAGTALON ; Manuelito MADRID
Philippine Journal of Pathology 2026;11(1):20-29
BACKGROUND
Breast cancer remains a leading malignancy among women globally. In addition to established factors like histopathology, hormone receptor status, and lymph node involvement, tools such as immunohistochemistry and molecular tests have been developed to assess tumor behavior and recurrence risk.
OBJECTIVEThis study investigates the concordance between the Ki-67 proliferation index measured by immunohistochemistry and the recurrence risk scores obtained from molecular genomic testing in patients with invasive breast cancer.
METHODOLOGYThis cross-sectional study included patients with invasive breast carcinoma at St. Luke’s Medical Center from 2019 to 2024, who underwent biopsy or mastectomy, with hormone status and Ki-67 index assessed by immunohistochemistry. All patients also had molecular genomic testing using either MammaPrint or OncotypeDX. Concordance between Ki-67 and the genomic recurrence risk score was evaluated using Kappa statistics, and results were further analyzed according to clinical risk and hormone receptor status.
RESULTSFifty-eight (58) patients met the study criteria. Most had grade 2, hormone receptor-positive, HER2-negative, and node-negative tumors, with high clinical risk based on Adjuvant! Online criteria (adapted from the MINDACT trial). The agreement between categorical Ki-67 and molecular recurrence risk was only fair: 66.7% for MammaPrint (kappa=0.35) and 60% for OncotypeDX (kappa = 0.29) using a 30% Ki-67 cutoff.
CONCLUSIONThere is a fair agreement between Ki-67 and the molecular genomic tests. These findings are consistent with prior studies reporting weak to moderate association. Despite the limited sample size, Ki-67 remains a practical and accessible risk stratification tool, particularly where genomic assays are unavailable. The study supports integrating Ki-67 with clinicopathologic and genomic data to guide therapy, reflecting current best-practice recommendations.
Human ; Female ; Breast Neoplasms
2.Exploring the Use of Computer-Aided Imaging for HER2 Immunohistochemistry Scoring in Breast Cancer: A Single-Center Experience in a Developing Country
Josh Matthew B. Chen ; Steffanie Charlyne A. Tamayo ; Manuelito A. Madrid
Philippine Journal of Pathology 2026;(75th PSP Research Competition Abstracts):1-
Background:
Contemporary breast cancer treatment relies on precise diagnostic categorization
for tailored therapy. HER2 status, assessed using immunohistochemistry (IHC), is a key biomarker
guiding the choice for the antibody-drug conjugate trastuzumab deruxtecan, which is effective
even in HER2-low/ ultralow breast cancer (defined as HER2 IHC score 0+, 1+ or 2+ without ISH
amplification). While manual slide interpretation of IHC is subjective and prone to inter- and intraobserver variability, digitization potentially enables computer-assisted image analysis to improve
accuracy. However, implementation and infrastructure barriers persist, especially in low- to middleincome countries such as the Philippines.
Objective:
This study evaluated the concordance between manual and AI-assisted HER2 IHC
scoring at St. Luke’s Medical Center – Quezon City (SLMC QC) and identified areas of discrepancy
and their possible causes.
Methodology:
This retrospective study included all Invasive Breast Carcinoma, No Special Type
(IBC, NST) tumors diagnosed on core needle biopsy and with HER2 IHC performed in SLMC QC
from January 1 to December 31, 2024. Original HER2 IHC slides were independently scored by
two breast pathology consultants; consensus results served as the ground truth. Slides were digitized
using Microvisioneer, and three regions of interest (with ≥ 100 tumor cells) selected by a senior breast
pathologist were analyzed using an AI-based image deconvolution algorithm to produce computer
image-enhanced HER2 scores. After a minimum of two-week washout, the senior breast pathologist
re-evaluated the digitized slides with AI-generated outputs to derive the Computer Image-Enhanced
(AI-Assisted) Scores. Concordance between ground truth and AI scores was then assessed.
Results:
A total of 161 HER2 IHC slides from patients with invasive breast carcinoma were
evaluated. Manual and AI-assisted scoring showed an overall percent agreement of 65.22% and a
Cohen’s kappa of 0.53, indicating moderate concordance. Weighted analysis demonstrated markedly
higher alignment (95.10% agreement; kappa 0.85, almost perfect). Discrepancies were most common
among manual scores of 0 to 2+, largely driven by background staining, whereas manual score 3+
classifications remained highly consistent with AI output.
Conclusion
The study supports the emerging role of AI as a valuable complementary tool in HER2
interpretation. With proper validation and integration, AI-assisted image analysis can strengthen
standardization in HER2 assessment, improving precision in patient care especially in resourcelimited settings.
Artificial Intelligence
3.Beyond the Bone: Extraskeletal Ewing Sarcoma Primary to the Breast in a 13-year-old Male
Jaeson M. Jimenez ; John Nicholas M. Pantoja ; Manuelito A. Madrid
Philippine Journal of Pathology 2026;(75th PSP Research Competition Abstracts):1-2
Introduction:
Extraskeletal Ewing sarcoma (EES) is a rare subtype of Ewing Sarcoma. It
is more common in older age group compared with Classic Ewing Sarcoma that is seen in
pediatric patients. It usually presents in the upper extremities, hips, and pelvis. The breast
is an unusual primary location for this tumor, and there are very few reported cases in the
literature. In the Philippines, there have been no reported cases yet of EES primary to the
breast in the pediatric age group.
Case Description:
This is a case of a right upper chest mass from a 13-year-old male noted
with progression of size for the past 8 months associated with pain. A biopsy was done in
the initial consult and yielded unremarkable results, hence management with unrecalled
antibiotics and pain medications. Continuous worsening of symptoms led to consultation at
our institution, wherein a non-tender, non-erythematous, non-movable, firm, 15 x 13 cm
mass was noted at the right chest during his ER consult and subsequent admission. CT
scan with contrast revealed a right chest wall mass (16.8 x 18.1 x 9.5 cm) with focal areas
of intrathoracic extension and associated pleural thickening. The patient subsequently
underwent an incision biopsy for further workup.
Microscopically, sheets and cords of small round blue cells are seen with scant to ample
amphophilic cytoplasm, increased nuclear to cytoplasmic ratio, coarse chromatin pattern, and
inconspicuous nucleoli set in a background of fibrocollagenous stroma. About 5-10 mitoses
are also seen per 10 high-power fields, some of which are atypical. Based on the patient’s
medical history, radiographic findings and histomorphologic characteristics of the case,
the primary working diagnosis for this case is a malignant small round blue cell neoplasm.
Immunohistochemistry studies showed strong, diffuse, membranous, and cytoplasmic
immunoreactivity to CD99, while the rest of the immunohistochemical stains (Desmin,
Myogenin, Chromogranin, CD45, and SALL4) yielded negative results. Additionally, NKX2.2
was also performed which showed strong, diffuse, nuclear immunoreactivity to the neoplastic
cells. The case is compatible with the diagnosis of Ewing Sarcoma. Subsequent molecular
test on ESWR1 via Fluorescence in-situ hybridization (FISH) revealed an ESWR gene
break apart, which further supports the diagnosis of Ewing Sarcoma. Six months after the biopsy, and having completed 3 cycles of chemotherapy, the patient
subsequently underwent excision of the mass. The excised tumor was submitted for
histopathologic evaluation, which showed good response (89% treatment effect, mainly
composed of extensive necrosis). There is no involvement of the adjacent rib bone, and all
surgical margins are negative for tumor; thus, this has been signed out as a case of Extraskeletal
Ewing Sarcoma of the Breast.
Discussion:
Extraskeletal Ewing Sarcoma (EES) is a highly aggressive tumor seen among
12% of patients with Ewing Sarcoma (ES). It has a wide anatomic distribution.Typically, it is
most common on the upper extremities, hips and pelvic area. It is also seen more among
older age group, usually in the 4th decade of life in some of the reported cases, in comparison
with classic ES. The breast is an unusual location for the tumor for both adult and pediatric
patients. Most tumors of the breast commonly seen in the pediatric age group are metastatic
processes, which include rhabdomyosarcoma and lymphoma. CD99 is an important and
essential immunohistochemical stain (IHC) in the diagnosis of Ewing sarcoma; 95% of cases
of ES has a diffuse, strong membranous expression. NKX2.2 is also useful in the diagnosis, as
it is more specific with ES. S100, ERG and FL1 can also be used to support the diagnosis of ES.
Molecular testing is also a requirement and helpful in the diagnosis of EES. The tumor is
associated with FET-ETS fusion genes. EWSR1-FLI1 fusion is the most common genetic
alteration with EES which resulted from translocation in the t(11;22)(q24;q12). Other mutation
of the tumor include ESWR-ERG1.
EES primary to the breast has a poorer prognosis despite multimodal treatments in comparison
to EES located in different sites with a good prognosis.
There have been nineteen (19) reported cases of EES primary to the breast. This accounts
for less than 1% of overall cases for EES. Currently, there have been no reported cases of EES
primary to the breast in the local setting.
Conclusion
Ewing sarcoma should still be considered as one of the main differential
diagnoses for pediatric patients presenting with soft tissue mass in the breast as well as in other
locations. Due to its aggressive clinical course, prompt diagnosis can help increase survivability,
surveillance of recurrence, and metastasis.
Child
;
Sarcoma, Ewing
;
Mutation
4.Upgrade rate and associated predictive factors of papillary breast lesions on core needle biopsy in a private tertiary institution: A cross-sectional study
Manuelito Madrid ; Nicole Dominique Santos
Philippine Journal of Pathology 2025;10(1):17-25
OBJECTIVE
The aim of this study was to determine the upgrade rate in diagnosis of biopsy-proven papillary breast lesions on core needle biopsy and their respective surgical excisions, and to assess for predictive factors associated with an upgrade at St. Luke’s Medical Center – Global City.
METHODOLOGYA retrospective review of our institution’s database identified 184 papillary breast lesions diagnosed by core needle biopsy. The study population consisted of 71 samples that met the inclusion criteria. The overall upgrade and concordance rates were determined and analyzed if there was any significant association with clinical demographics, radiologic findings, and core diameter on gross examination. Continuous variables were presented as mean and median, and Shapiro-Wilk test was used to assess normality of data. Categorical variables were expressed as frequencies and percentages. Simple logistic regression analysis with Firth’s bias correction was performed to determine the variables associated with a diagnostic upgrade. P values ≤0.05 were considered statistically significant.
RESULTSA total 71 patients, all female, were included in the study. The overall upgrade rate was 8.45% (95% CI: 3.16-17.49%) in comparison with the diagnosis of the initial CNB and SE alone. This translated to 6/71 samples in this study. The overall concordance was 91.55% based on clinical significance, and an individual diagnosis concordance rate of 78.87%. None of the predictive factors (i.e., age, history of breast cancer, BI-RADS score, and gross core diameter) assessed showed an association with a diagnostic upgrade.
CONCLUSIONThe computed overall upgrade rate is within range of currently published literature. The concordance rates for both clinical significance and individual diagnosis were quite high, suggesting good reproducibility of histopathologic diagnosis within our institution. This was also found to be consistent with other studies. Of the predictive factors, none showed an association to a diagnostic upgrade. Despite the latter, our findings may be of value within the medical center in further exploring and expanding the data set at hand, such that it may hopefully contribute to local guidelines in managing PBLs in the future.
Papilloma ; Biopsy, Core Needle
5.Breast panel biomarker changes after neoadjuvant chemotherapy in breast cancer
Kris Raychelle Godoy ; Manuelito Madrid
Philippine Journal of Pathology 2024;9(1):17-20
Objectives:
The aim of this study is to evaluate the breast panel biomarker changes and tumor intrinsic subtype after neoadjuvant chemotherapy among patients with residual invasive breast carcinoma whose breast specimens were processed at St. Luke’s Medical Center - Quezon City SLMC-QC) from 1 January 2017 to 30 June 2023.
Methodology:
Cases of residual invasive breast carcinoma status post neoadjuvant systemic therapy were identified by retrospective review of cases. The baseline characteristics, type of biopsy and resection procedures, pre – and post–neoadjuvant ER, PR and HER2 status and pre – and post–neoadjuvant tumor intrinsic subtype were analyzed using frequency and percentage. The comparison of the changes in pre- and post-neoadjuvant breast panel biomarkers were analyzed by using McNemar test while the changes in the intrinsic tumor subtype was done using Wilcoxon signed-rank test.
Results:
This study encompassed a total of 43 cases of residual invasive breast carcinoma following neoadjuvant systemic therapy. The data disclosed shifts in the breast molecular profile and intrinsic subtype post-administration of neoadjuvant systemic therapy. The alterations in hormone receptor status, ER and PR, were observed in 11.6% of cases, while HER-2 status exhibited changes in 2.3%. A 14% change in the tumor intrinsic subtype is observed. Among the initial 18 Luminal A cases, 1 transitioned to Luminal B, and among the 6 Luminal B cases, 2 become HER2 enriched subtypes. Furthermore, among the initial 12 HER2 enriched cases, three shifted to Luminal B, while all triple-negative cases remained unchanged after chemotherapy.
Conclusion
Based on our findings, alterations in the molecular profile of breast tumors, including shifts in intrinsic subtype after neoadjuvant chemotherapy (NAC), could impact patient prognosis. While the data generated from this study may not exhibit statistical significance, its clinical relevance is noteworthy. In summary, retesting of breast biomarkers in the resection specimen is recommended to accurately ascertain the appropriate use of targeted therapy.
Neoadjuvant Therapy
6.Ileo-Ileal Intussusception with Meckel Diverticulum in a Filipino adolescent
John Nicholas Pantoja ; Manuelito Madrid
Philippine Journal of Pathology 2023;8(2):53-56
Intussusception refers to the invagination (telescoping) of a part of the intestine into itself. Intussusception occurs primarily in infants and toddlers.1 The peak incidence is between 4 and 36 months of age, and it is the most common cause of intestinal obstruction in this age group. 2 Approximately 1 percent of cases are in infants younger than three months, 30 percent between 3 and 12 months, 20 percent between one and two years, 25 percent between two and three years, and 10 percent between three and four years.3 Although intussusception is most common in infants and young children, it is important to consider this diagnosis in children outside this age range. Approximately 10 percent of cases are in children over five years, and 3 to 4 percent in those over 10 years.3,4 We share here images from an actual case of a 15-year-old Filipino male with an ileo-ileal intussusception that is beyond the typical age range, with an incidental finding of an intraluminal mass that was histomorphologically diagnosed as Meckel’s diverticulum (MD). The diagnosis of intussusception is relatively rare in the patient’s age and the diagnosis of MD in the presence of intussusception is sparsely reported in the Philippines.
Intussusception refers to the invagination (telescoping) of a part of the intestine into itself. Intussusception occurs primarily in infants and toddlers.1 The peak incidence is between 4 and 36 months of age, and it is the most common cause of intestinal obstruction in this age group. 2 Approximately 1 percent of cases are in infants younger than three months, 30 percent between 3 and 12 months, 20 percent between one and two years, 25 percent between two and three years, and 10 percent between three and four years.3 Although intussusception is most common in infants and young children, it is important to consider this diagnosis in children outside this age range. Approximately 10 percent of cases are in children over five years, and 3 to 4 percent in those over 10 years.3,4 We share here images from an actual case of a 15-year-old Filipino male with an ileo-ileal intussusception that is beyond the typical age range, with an incidental finding of an intraluminal mass that was histomorphologically diagnosed as Meckel’s diverticulum (MD). The diagnosis of intussusception is relatively rare in the patient’s age and the diagnosis of MD in the presence of intussusception is sparsely reported in the Philippines.
Meckel Diverticulum
;
Strabismus
;
Adolescent
7.Submandibular secretory carcinoma in a 10-year-old Filipino
John Nicholas Pantoja ; Francisco Tria IV ; Manuelito Madrid
Philippine Journal of Pathology 2022;7(2):46-49
Secretory carcinoma is a recently described salivary gland neoplasm reported in the fourth edition of World Health Organization classification of head and neck tumors.1 We report a case of a primary secretory carcinoma arising from the submandibular gland that was completely excised in a 10-year-old. The histomorphologic features and the immunophenotype studies are compatible with secretory carcinoma. Unless proven otherwise by immunohistochemical stains and cytogenetics, secretory carcinoma should be included as a differential in cases of lesion of the major and minor salivary glands that has the primary differential diagnosis of acinic cell carcinoma. This case report aims to contribute to the limited literature about this disease entity and would be one of the few reported cases of the disease in a school-age child.
8.Rapid respiratory panel testing for SARS-CoV-2: Experience in a Private Tertiary Hospital
Steffanie Charlyne Tamayo ; Jose Jasper Andal ; Manuelito Madrid ; Evelina Lagamayo ; Raymundo Lo ; Daphne Ang
Philippine Journal of Pathology 2022;7(2):50-53
SARS-CoV-2 has infected more than 643 million individuals worldwide and accounts for close to 64,950 deaths in the Philippines. Due to COVID-19’s clinical overlap with other diseases and non-specific radiologic findings, its diagnosis rests primarily on laboratory methods, including reverse transcription polymerase chain reaction (RT-PCR) and multiplexed molecular platforms for rapid syndromic testing. Compared to RT-PCR which has a turnaround time of 24 to 72 hours, multiplexed molecular platforms can provide alternative diagnoses to COVID-19 in an average of one hour, providing meaningful data that can impact clinical and resource management when handling acute surge of patients with respiratory symptoms.
COVID-19
;
SARS-CoV-2
9.Metachronous primary cerebral rhabdomyosarcoma after treatment of Oral Primitive Neuroectodermal Tumor/Ewing’s Sarcoma in a school-aged girl: A case report
Danielle Anne Gonong ; Manuelito Madrid
Philippine Journal of Pathology 2020;5(2):53-59
Multiple primary malignancies are defined as two or three malignant neoplasms arising in different organ systems. Several cases of multiple primary malignancies are emerging in recent years due to the advancement in medical therapy and diagnostics. Multiple primary malignancies are not uncommon occurring at 0.7-16% of cancer patients, however, reported cases of multiple primary sarcomas are sparse. Presented in this report is a pediatric patient diagnosed with primary metachronous cerebral
rhabdomyosarcoma after being treated for primitive neuroectodermal tumor/Ewing’s sarcoma of the oral cavity. Despite limited cases addressing multiple primary sarcomas, this entity must not be overlooked as it is associated with a meager outcome compared to an index case of sarcoma alone.
Sarcoma, Ewing
;
Neuroectodermal Tumors, Primitive
;
Rhabdomyosarcoma
;
Immunohistochemistry
10.Clinico-radiologic, laboratory, and histopathologic profile of patients diagnosed with neonatal cholestasis at Philippine Children's Medical Center.
Gil Bryan B. Galvan ; Manuelito A. Madrid
The PCMC Journal 2017;13(1):49-63
BACKGROUND: Neonatal Cholestasiswarrants early, accurate and prompt intervention and comprises a wide spectrum of differential diagnosis which present with overlapping features, thus making a diagnosis difficult.
OBJECTIVE: To evaluate the clinical and laboratory parameters that could aid to differentiate between intrahepatic and extrahepatic neonatal cholestasis.
METHODS: Retrospective and Descriptive study of Neonatal Cholestasis patients who underwent Liver Biopsy and admitted at the Philippine Children's Medical Center from January 2007 to December 2011.
RESULTS: Factors that favor an intrahepatic cause of Cholestasis are ultrasound finding of a normal gallbladder, marked degree of giant cell transformation and presence of extramedullary hematopoiesis. Factors that favor an Extrahepatic cause of Cholestasis are presence of Splenomegaly, markedly elevated GGT, and histopathology findings of Portal and Periportal Ductal proliferation, bile plugs, lesser degree of giant cell transformation, septal fibrosis and cirrhosis, portal and neoductular cholestasis, and Portal-Portal bridges.
CONCLUSION: In this study, meticulous history and physical examination aid in the diagnosis of Neonatal Cholestasis. Splenomegaly and markedly elevated serum GGT are suggestive of Biliary Atresia, and a normal Gallbladder by Ultrasound favors Neonatal Hepatitis. Although there is significant overlap of histopathologic findings of patients with neonatal cholestasis, certain parameters favor an extrahepatic over an intrahepatic process.
Human ; Cholestasis


Result Analysis
Print
Save
E-mail