Evaluation of programmed cell death ligand 1 expression in a contemporary cohort of penile squamous cell carcinoma and its correlation with clinicopathologic and survival parameters: A study of 134 patients.

OBJECTIVES: Penile squamous cell carcinomas (PCs) are rare malignancies with a dismal prognosis in a metastatic setting; therefore, novel immunotherapeutic modalities are an unmet need. One such modality is the immune checkpoint molecule programmed cell death ligand 1 (PD-L1). We sought to analyze PD-L1 expression and its correlation with various clinicopathologic parameters in a contemporary cohort of 134 patients with PC. METHODS: A cohort of 134 patients with PC was studied for PD-L1 immunohistochemistry. The PD-L1 expression was evaluated using a combined proportion score with a cutoff of 1 or higher to define positivity. The results were correlated with various clinicopathologic parameters. RESULTS: Overall, 77 (57%) patients had positive PD-L1 expression. Significantly high PD-L1 expression was observed in high-grade tumors (P = .006). We found that 37% of human papillomavirus (HPV)-associated subtypes and 73% of other histotype tumors expressed PD-L1, while 63% of HPV-associated tumors and 27% of other histotype tumors did not (odds ratio, 1.35; P = .002 when compared for HPV-associated groups vs all others). Similarly, PD-L1-positive tumors had a 3.61-times higher chance of being node positive than PD-L1-negative tumors (P = .0009). In addition, PD-L1 high-positive tumors had a 5-times higher chance of being p16ink4a negative than PD-L1 low-positive tumors (P = .004). The PD-L1-positive tumors had a lower overall survival and cancer-specific survival than PD-L1-negative tumors. CONCLUSIONS: Overall, PD-L1 expression is associated with high-grade and metastatic tumors. Lower PD-L1 expression is observed more frequently in HPV-associated (warty or basaloid) subtypes than in other, predominantly HPV-independent types. As a result, PD-L1 positivity, including higher expression, portends lower overall and cancer-specific survival. These data provide a rational for further investigating PD-L1-based immunotherapeutics in PC.

Multifaceted Spindle Cell/Sclerosing Rhabdomyosarcoma With Role of Immunohistochemistry in Avoiding Misdiagnosis: A Multi-Institutional Study of 45 Distinct Tumors.

Background. Spindle cell/sclerosing rhabdomyosarcoma is a rare neoplasm and has an aggressive clinical course. Because of its rarity, we performed a multi-institutional collaboration to comprehend the overarching clinical, histopathological, and immunohistochemical characteristics of a cohort of spindle cell/sclerosing rhabdomyosarcoma. Materials and Methods. Forty-five patients with spindle cell/sclerosing rhabdomyosarcoma were identified. Demographics, clinical, histopathological, and immunohistochemistry data were reviewed and recorded. Results. The patients' age ranged from 1 to 85 years with a male to female ratio of 1.2:1. There were 15 children/adolescents and 30 adults. Eighteen (40%) tumors were located in the head and neck region. Twenty-four (53%) tumors displayed a bimorphic cellular arrangement with hypercellular areas having short, long, and sweeping fascicular and herringbone pattern, and hypocellular areas with stromal sclerosis and associated hyalinized and/or chondromyxoid matrix. Histomorphological differentials considered were leiomyosarcoma, malignant peripheral nerve sheath tumor, fibrosarcoma, nodular fasciitis, liposarcoma, synovial sarcoma, sarcomatoid carcinoma, solitary fibrous tumor, dermatofibrosarcoma protuberans, and schwannoma. Six tumors exhibited marked stromal sclerosis. The myogenic nature was confirmed by immunohistochemistry. Positivity for at least one skeletal muscle-associated marker (MyoD1 and/or myogenin) was observed. Conclusion. Spindle cell/sclerosing rhabdomyosarcoma diagnosis can be challenging as a number of malignant spindle cell neoplasm mimic this entity. Thus a correct diagnosis requires immunohistochemical work up with a broad panel of antibodies. In view of rarity of this neoplasm, further studies on a large cohort of patients with clinical follow-up data are needed for a better understanding of this tumor.

Diagnostic Utility of GATA3 and ISL1 in Differentiating Neuroblastoma From Other Pediatric Malignant Small Round Blue Cell Tumors.

Accurate diagnosis of neuroblastoma may be challenging, especially with limited or inadequate specimen and at the metastatic sites due to overlapping imaging, histopathologic, and immunohistochemical (immunohistochemistry [IHC]; infidelity among various lineage-associated transcription factors eg FLI1, transducin-like enhancer 1, etc) features. GATA3 and ISL1 have recently been described as markers of neuroblastic differentiation. This study aims at determining the diagnostic utility of GATA3 and ISL1 in differentiating neuroblastoma from other pediatric malignant small round blue cell tumors.We evaluated GATA3 and ISL1 expression in 74 pediatric small round blue cell tumors that included 23 NMYC-amplified neuroblastomas, 11 EWSR1-rearranged round cell sarcomas, 7 SYT::SSX1-rearranged synovial sarcomas, 5 embryonal rhabdomyosarcomas, 10 Wilms tumors (nephroblastomas), 7 lymphoblastic lymphoma, 7 medulloblastoma, and 4 desmoplastic small round cell tumor.All 23 neuroblastomas (moderate to strong staining in >50% of the tumor cells), 5 T-lymphoblastic lymphomas (moderate to strong staining in 40%-90% of the tumor cells), and 2 desmoplastic small round cell tumors (weak to moderate staining in 20%-30% of the tumor cells) expressed GATA3, while other tumors were negative. ISL1 immunoreactivity was observed in 22 (96%) neuroblastomas (strong staining in in >50% of the tumor cells, n = 17; moderate to strong staining in 26%-50% of the tumor cells, n = 5), 3 embryonal rhabdomyosarcoma (moderate to strong staining in 30%-85% of the tumor cells), 1 synovial sarcoma (weak staining in 20% of the tumor cells), and 7 medulloblastoma (strong staining in 60%-90% of the tumor cells). Other tumors were negative. Overall, GATA3 showed 86% specificity, 100% sensitivity, and 90% accuracy for neuroblastoma, with a positive predictive value (PPV) and negative predictive value (NPV) of 77% and 100%, respectively. ISLI showed 72% specificity, 96% sensitivity, and 81% accuracy for neuroblastoma, with a PPV and NPV of 67% and 97%, respectively. After the exclusion of T-lymphoblastic lymphoma and desmoplastic small round cell tumors, GATA3 had 100% specificity, sensitivity, accuracy, and PPV and NPV for neuroblastoma. Similarly, in pediatric small round blue cell tumors, ISL1 had 100% specificity, sensitivity, accuracy, PPV, and NPV for neuroblastoma, after embryonal rhabdomyosarcoma, synovial sarcoma, and medulloblastoma were excluded. CONCLUSIONS: GATA3 and ISL1 may be valuable in the diagnostic work-up of neuroblastoma and may reliably be used to support the neuroblastic lineage of pediatric small round blue cell tumors. Furthermore, dual positivity helps in challenging scenarios, when there is equivocal imaging, overlapping IHC features, limited specimen, and the lack of facility for a molecular work up.

Solitary Fibrous Tumor of the Kidney With Pure Round Cell Features: A Case Report With Review of Literature.

Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm known to occur at various soft tissue and visceral locations. Kidney is a rarely reported site for these tumors. Most of the SFTs described in the kidney exhibit a classical CD34-positive patternless spindle cell histology. Focal round cell morphology is seldom reported. Herein, we describe a 48-year-old male patient with renal SFT. This tumor had pure round cell morphology with a CD34-/STAT6+ immunophenotype. Fluorescent in situ hybridization and a multiplexed sequencing assay performed on an Illumina® HiSeq 4000 platform revealed NAB2 and STAT6 gene rearrangement. Renal tumors with round cell morphology are diagnostically challenging and SFT is not often considered in the differential diagnosis of a round cell tumor of the kidney. Moreover, a CD34-negative profile can be rather confounding while diagnosing such lesions. In such scenarios, a strong nuclear STAT6 immunostaining is extremely helpful in clinching the diagnosis. SFT should always be considered in the differential diagnosis of round cell tumors of the kidney due to significant diagnostic and therapeutic implications.

Precision Medicine in Bladder Cancer: Present Challenges and Future Directions.

Bladder cancer (BC) is characterized by significant histopathologic and molecular heterogeneity. The discovery of molecular pathways and knowledge of cellular mechanisms have grown exponentially and may allow for better disease classification, prognostication, and development of novel and more efficacious noninvasive detection and surveillance strategies, as well as selection of therapeutic targets, which can be used in BC, particularly in a neoadjuvant or adjuvant setting. This article outlines recent advances in the molecular pathology of BC with a better understanding and deeper focus on the development and deployment of promising biomarkers and therapeutic avenues that may soon make a transition into the domain of precision medicine and clinical management for patients with BC.

SS18-SSX Expression in a Contemporary Cohort of Primary Renal Synovial Sarcoma: A Multi-Institutional Experience of Fourteen Patients.

Primary renal synovial sarcoma is a rare aggressive mesenchymal neoplasm of the kidney that accounts for less than 1% of renal sarcomas. Herein, we describe the clinicopathologic and molecular findings of 14 renal synovial sarcoma patients in one of the largest case series to date and to our knowledge, the only renal synovial sarcoma series to use novel SS18-SSX IHC. Clinicopathologic, IHC, molecular, management, and follow-up data were reviewed and analyzed. Macroscopically, the tumors had either homogeneous, tan-white, and solid (n = 10), variegated and solid (n = 3), or variegated and solid-cystic (n = 1) cut surfaces. Spindle cell (n = 10), round cell (n = 3), and round to epithelioid morphologies (n = 1) were observed. SS18-SSX IHC was positive in all 14 tumors (diffuse, n = 10; multifocal, n = 2; focal, n = 2). All the tumors harbored SS18::SSX1/2 gene rearrangement. Metastases to the liver, brain, and lung (n = 1); liver and bone (n = 1); liver and diaphragm (n = 1) were identified. Adjuvant chemotherapy was administered in 11/12 patients. Follow-up was available for 10 patients (time period range: 5 to 24 months). Four patients died of disease, and six patients are alive with no recurrence or metastasis. As SS18-SSX IHC showed an excellent concordance with the FISH results, this may reliably be used in the IHC panel of spindle/round cell sarcomas of the kidney and as a molecular surrogate for renal synovial sarcoma, particularly in a resource-limited setting. Also, the tumors with focal SS18-SSX expression had lower break apart signals in the FISH assay (19% and 23% in two tumors with focal SS18-SSX IHC positivity).

Multicystic Solitary Fibrous Tumor of the Kidney: A Case Report With Review of Literature.

Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm known to occur at various soft tissue and visceral locations. Kidney is one of the rare locations for these tumors with around 64 cases being available in the literature. Most of the renal SFTs are tan-white, solid, firm, unencapsulated, and lobulated masses. A predominantly cystic renal SFT has never been reported in the literature. Herein we describe a case of multicystic renal SFT in a 44-year-old male with the characteristic CD34 + /STAT6 + immunophenotype. A careful gross and microscopic examination is warranted while dealing with cystic spindle cell neoplasms of the kidney and SFT should always be considered in the differential diagnosis. STAT6 immunohistochemistry is quite specific for the diagnosis. Moreso, a detailed immunopanel is necessary to exclude other spindle cell neoplasms of the kidney because of significant therapeutic and prognostic implications.

The 2022 revision of the World Health Organization classification of tumors of the urinary system and male genital organs: advances and challenges.

The fifth edition of the World Health Organization (WHO) classification of urinary and male genital organ tumors has been recently published in 2022. The application of molecular profiling has made a substantial impact on the classification of urologic tumors. The new WHO classification introduces a group of molecularly well-defined renal tumor subtypes. The significant changes include addition of a category of "other oncocytic tumors" with oncocytoma/chromophobe renal cell carcinoma (chRCC)-like features, elimination of the subcategorization of type 1/2 papillary RCC, and inclusion of eosinophilic solid and cystic RCC as an independent tumor entity. The WHO/ISUP grading now has been recommended for all RCCs. Major nomenclature changes include replacement of histologic "variants" by "subtypes," "clear cell papillary renal cell carcinoma" to "clear cell renal cell tumor," "TCEB1-mutated RCC" to "ELOC-mutated RCC," "hereditary leiomyomatosis and renal cell carcinoma" to "fumarate hydratase-deficient RCC," "RCC-Unclassified" to "RCC-NOS," "primitive neuroectodermal tumor" to "embryonic neuroectodermal tumor," "testicular carcinoid" to "testicular neuroendocrine tumor," and "basal cell carcinoma of the prostate" to "adenoid-cystic (basal-cell) carcinoma of the prostate." Metastatic, hematolymphoid, mesenchymal, melanocytic, soft tissue, and neuroendocrine tumors are collectively discussed in separate chapters. It has been suggested that the morphological classification of urothelial cancer be replaced with a new molecular taxonomic classification system.

Reporting Trends, Practices, and Resource Utilization in Neuroendocrine Tumors of the Prostate Gland: A Survey among Thirty-Nine Genitourinary Pathologists.

Background. Neuroendocrine differentiation in the prostate gland ranges from clinically insignificant neuroendocrine differentiation detected with markers in an otherwise conventional prostatic adenocarcinoma to a lethal high-grade small/large cell neuroendocrine carcinoma. The concept of neuroendocrine differentiation in prostatic adenocarcinoma has gained considerable importance due to its prognostic and therapeutic ramifications and pathologists play a pivotal role in its recognition. However, its awareness, reporting, and resource utilization practice patterns among pathologists are largely unknown. Methods. Representative examples of different spectrums of neuroendocrine differentiation along with a detailed questionnaire were shared among 39 urologic pathologists using the survey monkey software. Participants were specifically questioned about the use and awareness of the 2016 WHO classification of neuroendocrine tumors of the prostate, understanding of the clinical significance of each entity, and use of different immunohistochemical (IHC) markers. De-identified respondent data were analyzed. Results. A vast majority (90%) of the participants utilize IHC markers to confirm the diagnosis of small cell neuroendocrine carcinoma. A majority (87%) of the respondents were in agreement regarding the utilization of type of IHC markers for small cell neuroendocrine carcinoma for which 85% of the pathologists agreed that determination of the site of origin of a high-grade neuroendocrine carcinoma is not critical, as these are treated similarly. In the setting of mixed carcinomas, 62% of respondents indicated that they provide quantification and grading of the acinar component. There were varied responses regarding the prognostic implication of focal neuroendocrine cells in an otherwise conventional acinar adenocarcinoma and for Paneth cell-like differentiation. The classification of large cell neuroendocrine carcinoma was highly varied, with only 38% agreement in the illustrated case. Finally, despite the recommendation not to perform neuroendocrine markers in the absence of morphologic evidence of neuroendocrine differentiation, 62% would routinely utilize IHC in the work-up of a Gleason score 5 + 5 = 10 acinar adenocarcinoma and its differentiation from high-grade neuroendocrine carcinoma. Conclusion. There is a disparity in the practice utilization patterns among the urologic pathologists with regard to diagnosing high-grade neuroendocrine carcinoma and in understanding the clinical significance of focal neuroendocrine cells in an otherwise conventional acinar adenocarcinoma and Paneth cell-like neuroendocrine differentiation. There seems to have a trend towards overutilization of IHC to determine neuroendocrine differentiation in the absence of neuroendocrine features on morphology. The survey results suggest a need for further refinement and development of standardized guidelines for the classification and reporting of neuroendocrine differentiation in the prostate gland.

Solitary Fibrous Tumor of the Adrenal Gland.

OBJECTIVES: Solitary fibrous tumor (SFT) is a mesenchymal neoplasm that can arise at various anatomic locations. It is characterized by inv12(q13q13)-derived NAB2::STAT6 fusion, resulting in the nuclear expression of STAT6. Primary SFT of the adrenal gland is rare. We launched a multi-institutional collaboration to comprehend the overarching demographics, clinical and follow-up, macroscopic, microscopic, IHC, and FISH features of 9 patients with SFT of the adrenal gland. METHODS: We added a series of 9 patients to the collection of adrenal SFTs where the clinicopathologic parameters, including clinical presentation, imaging, histopathology, IHC, molecular profiles, and management and follow-up data, were analyzed comprehensively. A modified 4-variable risk stratification model, including age, tumor size, and necrosis, was applied. RESULTS: Our series consisted of 6 male and 3 female patients, ranging in age from 19 to 64 years (mean, 49.3 years). Abdominal pain (4) and fever with abdominal pain (1) were the presenting symptoms in 5 patients. In the remaining 4 patients, the tumors were detected by abdominal imaging for hypertension and diabetes. The size of the tumor ranged from 2 cm to 10.5 cm in maximum dimension. All tumors exhibited the morphology of a spindle cell SFT with a patternless architecture; 3 had a focal storiform arrangement. STAT6 positivity was observed in all tumors, and 7 were positive for CD34. Surgical resection was the primary modality of treatment. No adjuvant therapy was administered. Follow-up ranging from 7 months to 23 months was available for 7 patients. All were alive without disease recurrence or metastasis. Risk stratification placed 8 (88.9%) patients into a low-risk category and 1 into an intermediate-risk category. CONCLUSIONS: This series is the largest of adrenal SFTs to date. These tumors of the adrenal gland are predominantly spindle cell neoplasms with indolent behavior, with a wide age distribution and a slight male preponderance. Combining our cohort with the previously published cases, the majority of tumors fall into the low-risk category for the propensity to develop metastases. Owing to the rarity and age distribution associated with these tumors, the differential diagnosis is wide and requires a systematic approach for ruling out key differential diagnoses aided by STAT6 IHC.

Primary extraskeletal myxoid chondrosarcoma of the breast: report of a case and literature review.

Primary extraskeletal myxoid chondrosarcoma (pEMC) of the breast is rare and only a few cases have been reported to date. Herein, we report a case of primary EMC of the breast in a 45-year-old female. The patient presented with a left breast mass for 1 month. Mammogram revealed a fairly circumscribed mass with spicules of calcifications. The core biopsy and resection specimen showed a myxoid soft tissue neoplasm with histologic features of a myxoid chondrosarcoma. Necrosis, hemorrhage, and brisk mitotic activity were present. No malignant epithelial element was identified even after extensive sampling. The tumor cells exhibited immunoreactivity for vimentin, S100, neuron specific enolase, CD99, and synaptophysin, while the epithelial, myoepithelial, and mammary lineage-associated markers were negative. As up to 81% of EMC cases harbor t(9;22)(q22;q12), this results in a fusion of EWS RNA-binding protein 1 gene (EWSR1) at 22q12 to the nuclear receptor subfamily 4, group A, member 3 gene at 9q22. A rearrangement involving the EWSR1 locus was detected in our case. Whole body PET-CT did not reveal any other mass. A diagnosis of pEMC was rendered. The patient received six cycles of 5-Fluorouracil, Cyclophosphamide, and Adriamycin. The patient was in clinical and radiologic remission at the last follow-up (18 months post surgery). PET-CT and brain MRI were negative. In conclusion, surgical pathologists should include EMC in their differential while dealing with a myxoid soft tissue lesion of the breast, particularly in the core needle biopsies. An expeditious diagnosis of EMC of the breast would allow the surgeon to carry out conservative breast surgery instead of more radical approaches taken in cases of other primary malignant mammary neoplasms.

Does Immunohistochemistry Add to Morphology in Differentiating Trichoepithelioma, Desmoplastic Trichoepithelioma, Morpheaform Basal Cell Carcinoma, and Microcystic Adnexal Carcinoma?

BACKGROUND: The distinction among cutaneous basaloid neoplasms such as trichoepithelioma (TE), desmoplastic trichoepithelioma (DTE), morpheaform basal cell carcinoma (MBCC), and microcystic adnexal carcinoma (MAC) can be difficult, especially in superficial biopsies. As the treatment plan of each entity is different, accurate characterization is important for appropriate management. While TE and DTE are benign neoplasms with indolent behavior, MBCC and MAC are typically locally aggressive. The expression of several recently described immunohistochemical (IHC) markers, including p40, IMP3, and ProEx C, has not been adequately established in cutaneous neoplasms. We explored the potential utility of a broad IHC panel, including previously reported and novel markers to differentiate TE, DTE, MBCC, and MAC. DESIGN: A total of 35 archival cases [TE (n=14), DTE (n=9), MBCC (n=6), and MAC (n=6)] were stained with 9 IHC markers: p40, IMP3, ProEx C, p16, CK20, Ki-67, androgen receptor, D2-40, and beta-catenin. Tumors with >5% immunoreactivity were scored as positive. The intensity was scored on a scale from 1+ to 3+. The pattern of positivity- nuclear, cytoplasmic, membranous, or in combination; peripheral or central distribution with lesion was also recorded. RESULTS: CK20 (in contrast to prior studies) and IMP3 were negative in all cases. Likewise, with the exception of one case of TE, androgen receptor showed no immunoreactivity in all categories. No significant difference was observed in the expression of beta-catenin, p16, ProEx C, and p40 among the four groups of cutaneous neoplasms. The mean Ki-67 labeling index for MBCC (8%) was slightly higher than DTE (3%). Interestingly, the proliferation index for TE (15%) was significantly higher than that of MBCC. All six cases of MAC and 36% of TEs expressed D2-40; neither the MBCC nor DE cases showed D2-40immunoreactivity. Also, we confirmed the previously published observation of scattered CK20 positive Merkel cells in the epidermis of all cases of DTE; whereas, no Merkel cells were identified in MBCC and MAC cases. CONCLUSIONS: Except Ki-67, our IHC panel showed no significant added diagnostic utility of IHC in discriminating among TE, DTE, MBCC, and MAC. Among the four cutaneous neoplasms, DTE and MBCC show a small but discernible difference in Ki-67.

COVID-19 pandemic impact on cytopathology practice in the post-lockdown period: An international, multicenter study.

BACKGROUND: In a previous worldwide survey, the authors showed a drastic reduction in the number of cytological specimens processed during the coronavirus disease 2019 "lockdown" period along with an increase in malignancy rates. To assess the continued impact of the pandemic on cytological practices around the world, they undertook a second follow-up worldwide survey collecting data from the post-lockdown period (2020). METHODS: Participants were asked to provide data regarding their cytopathology activity during the first 12 weeks of their respective national post-lockdown period (2020), which ranged from April 4 to October 31. Differences between the post-lockdown period and the corresponding 2019 period were evaluated, and the authors specifically focused on rates of malignant diagnoses. RESULTS: A total of 29 respondents from 17 countries worldwide joined the survey. Overall, a lower number of cytological specimens (n = 236,352) were processed in comparison with the same period in 2019 (n = 321,466) for a relative reduction of 26.5%. The overall malignancy rate showed a statistically significant increase (12,442 [5.26%] vs 12,882 [4.01%]; P < .001) during the same time period. Similar results were obtained if both malignancy and suspicious for malignancy rates were considered together (15,759 [6.58%] vs 16,011 [4.98%]; P < .001). CONCLUSIONS: The data showed a persistent reduction in the cytological specimen volume during the post-lockdown period (2020). However, the relative increase in the cytological workload in the late part of the post-lockdown is a promising finding of a slow return to normality.

Global impact of the COVID-19 pandemic on cytopathology practice: Results from an international survey of laboratories in 23 countries.

BACKGROUND: To the authors' knowledge, the impact of the coronavirus disease 2019 (COVID-19) pandemic on cytopathology practices worldwide has not been investigated formally. In the current study, data from 41 respondents from 23 countries were reported. METHODS: Data regarding the activity of each cytopathology laboratory during 4 weeks of COVID-19 lockdown were collected and compared with those obtained during the corresponding period in 2019. The overall number and percentage of exfoliative and fine-needle aspiration cytology samples from each anatomic site were recorded. Differences in the malignancy and suspicious rates between the 2 periods were analyzed using a meta-analytical approach. RESULTS: Overall, the sample volume was lower compared with 2019 (104,319 samples vs 190,225 samples), with an average volume reduction of 45.3% (range, 0.1%-98.0%). The percentage of samples from the cervicovaginal tract, thyroid, and anorectal region was significantly reduced (P < .05). Conversely, the percentage of samples from the urinary tract, serous cavities, breast, lymph nodes, respiratory tract, salivary glands, central nervous system, gastrointestinal tract, pancreas, liver, and biliary tract increased (P < .05). An overall increase of 5.56% (95% CI, 3.77%-7.35%) in the malignancy rate in nongynecological samples during the COVID-19 pandemic was observed. When the suspicious category was included, the overall increase was 6.95% (95% CI, 4.63%-9.27%). CONCLUSIONS: The COVID-19 pandemic resulted in a drastic reduction in the total number of cytology specimens regardless of anatomic site or specimen type. The rate of malignancy increased, reflecting the prioritization of patients with cancer who were considered to be at high risk. Prospective monitoring of the effect of delays in access to health services during the lockdown period is warranted.