PurposeGenetic mutations in the tumor suppressor gene APC and the oncogene KRAS are an initial event in the colorectal adenoma-carcinoma sequence. Multistep carcinogenesis has been discovered through the study of familial adenomatous polyposis (FAP), an inherited disease with a germline APC variant. We aimed to determine the premalignant mutational genotypes that progress to colorectal neoplasia using target sequencing to compare the characteristics of FAP patients with sporadic cases.Experimental designA total of 197 samples from 20 FAP and 13 sporadic cases were analyzed using next-generation sequencing (NGS) with a cancer panel. The analysis of APC germline variants identified FAP patients with a germline variant, those with whole APC deletion, and those with no alterations. The association between pathogenic germline variants and somatic mutations was assessed.ResultsColorectal tumors of FAP and non-polyposis patients showed a similar frequency of mutations (APC, 76% and 75%; KRAS, 32% and 25%). Somatic APC mutations in FAP patients was observed in the mutation cluster region (63.3%). In FAP, many colorectal tumors (57.5%) harbored two APC hits, whereas in sporadic cases, one or two hits were more common (44.4% and 22.2%, respectively). Of the 99 tumors in FAP patients with APC germline variants as the first hit, 74 tumors (74.7%) acquired somatic mutations as the second hit, and 9 tumors (9.9%) further gained a third hit, indicating a ‘three-hit’ alteration.ConclusionAn identical cancer pathway may be associated with multistep carcinogenesis, accompanied by APC mutations in mutation hotspots. A combined analysis of germline and somatic alterations revealed ‘three-hit’ alterations in the APC gene among the FAP patients, suggesting that the heterogeneity of colorectal carcinogenesis contribute to these genetic changes.

Solitary fibrous tumors (SFTs) of the central nervous system (CNS) are rare mesenchymal tumors characterized by a fusion of the NGFI-A-binding protein 2 (NAB2) gene and the signal transducer and activator of transcription 6 (STAT6) gene, immunohistochemically resulting in nuclear expression of STAT6 - an immunohistochemical hallmark essential for diagnosis, as outlined in the fifth edition of the World Health Organization Classification of Tumors. Dedifferentiation, where low-grade tumors transform into high-grade forms, has been observed in SFTs, with documented cases involving sarcomatous or rarely epithelial transformations. We report the first case of a CNS SFT exhibiting "transdedifferentiation" into epithelioid neuroendocrine differentiation. A 36-year-old woman presented with worsening frontal headaches and vision deterioration due to an 8.2-cm frontal tumor with skull erosion. Histologically, the tumor consisted of predominantly high-grade undifferentiated epithelioid round cells that expressed STAT6, along with multifocal synaptophysin and chromogranin A positivity, and occasional cytokeratin and claudin-4 reactivity, resembling large cell neuroendocrine carcinoma. A minor bland spindle cell component with STAT 6 immunoreactivity was also noted. This case highlights the rare occurrence of neuroendocrine "transdedifferentiation" in CNS SFTs. This case highlights the importance of recognizing dedifferentiation in CSF SFTs, which often correlates with aggressive tumor behavior and poor prognosis. Given the rarity of neuroendocrine "transdedifferentiation," this case adds valuable insight into the diverse dedifferentiation patterns seen in CNS SFTs, emphasizing the need for accurate diagnosis to guide appropriate treatment strategies.

Meningiomas are the most diagnosed primary central nervous system tumor. Currently, 15 different subtypes of meningioma exist with various characteristics. One extremely rare subtype is myxoid meningioma, which is a World Health Organization grade 1 benign meningioma. These specific meningiomas have only been reported 12 times in the literature. In this representative case, we present a 46-year-old female patient with a left frontal myxoid meningioma, describe the findings on imaging, and provide the histopathological features that are needed for diagnosis. Furthermore, this report discusses the other existing myxoid meningioma case reports found throughout the literature.

A 60-year-old woman presented with a 3-year history of a slow-growing, painless mass in their left parotid gland. Ultrasonography revealed a well-circumscribed, lobulated, hypoechoic mass measuring 19x12x10 mm in the left parotid gland. Computed tomography revealed a well-circumscribed, solid mass with homogeneous enhancement. Fluorodeoxyglucose-positron emission tomography revealed uptake by the tumor but no uptake in other organs, including the nasopharynx. The patient underwent superficial parotidectomy with adequate safety margins and selective neck dissection followed by radiotherapy. No facial paralysis or recurrence of the tumor had been observed as of 20 months post-operation. Histologically, the tumor was composed of sheets of syncytial cancer cells with prominent nucleoli in a dense lymphoplasmacytic background. Epstein-Barr virus (EBV)-encoded RNA in situ hybridization was diffusely positive in the tumor cells. These findings indicated that the tumor was an EBV-associated lymphoepithelial carcinoma. Metastasis, especially from the nasopharynx, was excluded endoscopically and radiologically. Targeted next-generation sequencing of 160 cancer-related genes using the surgical specimen revealed no mutations, including known significant mutations detected in EBV-associated nasopharyngeal carcinoma.

Human telomerase reverse transcriptase (hTERT) is highly expressed in various cancers, including breast cancer. Although telomere elongation is an essential role for hTERT, the nuclear export after oxdative stress has also been shown in several cancer cell lines and is associated with drug-resistance in vitro. As only a few reports focused on the subcellular localization of hTERT in clinical specimens, we performed immunohistochemistry (IHC) and analyzed the correlation between intracellular hTERT expression and the clinicopathological characteristics to identify the clinical significance of hTERT subcellular expression in breast cancers. 144 invasive breast cancers classified by IHC subtype without primary systemic therapy (PST), were selected from a surgical resection cohort and were immunostained for hTERT, p-STAT3, p-AKT and p-ERK. The nuclear and/or cytoplasmic staining intensity and proportion of hTERT were scored and compared with clinicopathological parameters. The nuclear hTERT expression was significantly correlated with HER2 expression (p=0.00156), and the scores were significantly correlated with p-STAT3 and p-AKT expression scores (r=0.532, p=0.000587 and r=0.345, p=0.0339, respectively) in the HER-2 immunopositive breast cancer including luminal-HER2 and HER2 subtypes. Furthermore, hTERT was expressed more in cytoplasm in the specimens after PST than those before PST, and the score tended to be negatively correlated with tumor shrinkage rate in HER2 subtype (r=-0.593, p=0.0705). These results suggest that nuclear and/or cytoplasmic hTERT may play a different role before and after PST including the tumorigenesis and drug-resistance in breast cancer. Suppression of cytoplasmic hTERT expression may lead to more effective strategy for drug-resistant HER2 subtype in breast cancer.

Polymorphous adenocarcinoma (PAC) is a rare variant of minor salivary gland tumors. Because of its architectural diversity, histological diagnosis of PAC can be difficult especially for small biopsies, and immunohistochemistry is of great help in differentiating it from its histologic mimics. The aim of this study is to conduct a systematic literature review to identify reliable immunohistochemical markers for PAC. We conducted an electronic literature search of the MEDLINE, ScienceDirect, SpringerLink, and Wiley Online Library databases, covering the literature published in the period between 1988 and 2021. The eligibility criteria included case reports and retrospective studies of PAC cases with details of immunohistochemical markers. Following the search and selection process, 32 studies with 409 cases were included in this systematic review. Overall, > 90% positivity was observed for pan-cytokeratin (CK) (97.3%), CK7 (96.8%), CK7/8 (97.4%), E-cadherin (90.0%), Vimentin (92.5%), S100 (97.0%), p63 (91.7%), and SOX10 (100%), while little to no positivity was observed for CK20 (0.0%), p40 (0.0%), and GFAP (5.0%). The average MIB-1 labeling index was 3.78%. The results of this systematic review indicate that CK7+/CK20-, p63+/p40-, S100+, Vimentin+, and GFAP- immunophenotype have diagnostic value for PAC. In addition, the use of S100, MSA, p40, and c-Kit provide additional layers of information helpful to differentiate PAC from adenoid cystic carcinoma, one of challenging differential diagnoses.

A 15-year-old old Japanese male with a 2-month history of swelling of his left subauricular area was admitted to our department. A thumb-sized, hard mass with mild tenderness was palpated on the left parotid gland. Ultrasonography revealed a well-circumscribed, hypoechoic mass exhibiting heterogeneity in the left parotid gland measuring 1.7 × 1.5 × 1.3 cm. Computed tomography scan revealed a well-circumscribed, solid mass exhibiting slight peripheral enhancement in the left parotid gland. Magnetic resonance imaging revealed a hypointense mass in the left parotid gland on both T1- and T2-weighted images. Clinicoradiologic findings suggested a benign or low-grade malignant parotid tumor. The patient underwent left superficial parotidectomy with adequate safety margins. The facial nerve was identified and preserved. Neither facial paralysis nor tumor recurrence was observed as of 1 year postoperatively. Histologically, the nodule consisted of a vaguely nodular arrangement of variably sized ducts and acini in a hyalinized fibrous background with focal myxoid changes. The ductal/acinar component exhibited a bilayered arrangement of cuboidal luminal and flattened abluminal cells exhibiting a variety of epithelial proliferative patterns, including micropapillary and cribriform. Areas of oncocyte-like changes with intracellular coarse eosinophilic granules, apocrine-like feature, foamy/vacuolated changes, and clear cells were noted in the proliferating epithelium. Immunohistologically, the luminal cells were positive for gross cystic disease fluid protein-15. The Ki-67 labeling index was 2–3%. The histologic features and immunohistologic profile were consistent with sclerosing polycystic adenosis. Targeted next-generation sequencing of 160 cancer-related genes using the surgical specimen revealed no mutations, including known significant mutations in PTEN, PIK3CA , or PIK3R1 .

Abstract Background: Since the discovery of the oncogenic mutation B-Raf proto-oncogene, serine threonine kinase (BRAF) V600E, dabrafenib and trametinib (DT) combination therapies have been shown to have great anti-tumor activities against V600E-mutated non-small cell lung cancers (NSCLC). However, the resistant mechanisms for DT therapies are not fully understood. Single nucleotide mutation in KRAS, NRAS, MEK1, which locate in the universal growth pathway RAF-RAS-MEK-ERK, or frameshift stop of PTEN had been reported as acquired resistances previously. We had been aimed to search a new therapeutic target for clinically DT resistant, and have been performed comprehensive cancer drug screening by establishment of the clinically resistant patient's derived cell lines. In the process, we focused on a positive regulator of cell cycle cyclin dependent kinase 4 (CDK4) as a potential role in resistant acquisition. Materials: Two patients' pleural effusion-derived NSCLC cell lines of BRAF V600E-mutant who were clinically resistant for DT therapies (LC-1, LC-6) were established and used for post-DT samples. The same patients' derived tissue samples collected at diagnosis (tLC-1, tLC-6) were used for pre-DT samples as comparison. Encompassing cancer drug screening were performed by MTS assay. Copy number variant (CNV) and single nucleotide variant (SNV) were analyzed by amplicon-captured next generation sequence (NGS). Each mRNA expression was quantified using TaqMan Array of human cancer drug panel. Protein expression were evaluated by western blotting and immunohistochemistry (IHC). As references for protein expression, we used patient's derived cell lines of BRAF K601E-mutant (LC-12), and BRAF V600E-mutant (OY) both of which were DT naive. Results: Patient 1 was treated with DT for 3 months and progressed with pleural effusions. Patient 6 was treated with DT for 11 months and progressed with pleural effusions. In both LC-1 and LC-6, dabrafenib and trametinib showed resistance in each 1microM screening in vitro. Analysis of CNV and SNV pre- and post-treatment in each patient, copy number of CDK4 was significantly gained in the patient 1 after DT therapies. qPCR and western blotting revealed high expression of CDK4 in LC-1 while not remarkable in LC-6, LC-12 and OY. Protein expression assessed by IHC revealed that in pre- and post-DT sample, increased protein expression of CDK4, cyclinD1 phosphorylated-Rb were observed in LC-1, but remarkable change were not observed in the patient 6. Conclusions: We highlight CDK4 copy number gain as a possible clinical resistant mechanism for DT therapies in BRAF V600E-mutated NSCLC. We are currently investigating how CDK4 contribute as the acquired resistance. Citation Format: Noriko Hirai, Takaaki Sasaki, Shinichi Chiba, Yuji Uno, Hidehiro Takei. CDK4 copy number gain in BRAF V600E-mutated non-small cell lung cancers resistant to dabrafenib plus trametinib [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1103.

Purpose: To report a case of external ophthalmoplegia due to an uncommon form of amyloidosis exclusively affecting the lateral rectus muscle, and to discuss the clinical manifestation, diagnostic challenges, and management pitfalls of isolated amyloidosis in the extraocular muscle. Observations: A 64-year-old woman presented with diplopia in her left gaze lasting for six months. She had orthophoria in the primary position and abduction limitation in the left eye. Routine laboratory examinations were unremarkable. Orbital magnetic resonance imaging showed fusiform enlargement of the left lateral rectus muscle, without tendon involvement. Extraocular muscle biopsy was recommended to make a diagnosis, which revealed amyloid deposition in the lateral rectus muscle. A systemic work-up showed no evidence of systemic amyloidosis. Therefore, a diagnosis of primary isolated amyloidosis was made. Orthophoria in the primary position and diplopia in the lateral gaze persisted at the six-month follow-up. Conclusions and importance: Atypical extraocular muscle enlargement should alert clinicians to the need for tissue biopsy to identify uncommon etiologies, such as amyloidosis. There are no pathognomonic or radiological features to distinguish localized from systemic amyloidosis. Therefore, if amyloidosis of the extraocular muscles is diagnosed, a systemic work-up is needed to rule out systemic amyloidosis, which is potentially life-threatening.

Triple-negative breast cancer (TNBC) has a poorer prognosis than other breast cancer subtypes; therefore, identifying markers of early recurrence is important. The present study aimed to establish a liquid biopsy protocol for droplet digital PCR-based detection of frequently mutated genes in patients with TNBC. Tumor DNA from 36 patients with TNBC who relapsed within 2 years after surgical resection was retrospectively analyzed. Somatic mutational profiles were evaluated using targeted sequencing to identify frequently mutated genes and genes associated with molecularly targeted therapies. The association between genetic alterations and associated protein phosphorylation was investigated using immunohistochemical analysis. Recurrent hot spot mutations in the plasma were monitored over time. Mutation-specific probes were used to successfully detect mutations in the blood samples of patients who were positive for PIK3CA H1047R and AKT1 E17K mutations. Somatic mutations in AKT1 (14.9%) and PIK3CA (25.5%) were frequently identified in the data. Robust phosphorylation of AKT and S6RP was more common in tumors with PIK3CA H1047R and AKT1 E17K mutational background than in tumors with wild-type PIK3CA and AKT1. In conclusion, the present study evaluated a high-sensitivity detection system for frequently mutated genes that was also applicable for cell-free DNA. The PI3K/AKT pathway was revealed to be activated in patients harboring PIK3CA H1047R and AKT1 E17K mutations; therefore, the PI3K/AKT pathway may be a promising candidate for targeted therapy in these patients.

Few cases of malignant transformation of supposedly low-grade gliomas were described in patients with neurofibromatosis type 1 (NF1). A 27-year-old man with NF1 presented with weakness of his lower extremities and was radiologically found to have a spinal intramedullary tumor primarily involving the Th11 level. The tumor histologically demonstrated features diagnosed as a low-grade astrocytoma, subtype indeterminate (WHO grade II). Immunohistochemically, GFAP was positive, and IDH1 R132H and BRAF V600E were negative. ATRX immunoreactivity was retained. Five years after the surgery, the intramedullary tumor extended to the levels from Th8 to L1 and was partially resected. It showed histologic features similar to those of the first tumor. Two years after the second surgery, the residual spinal cord tumor was found to widely involve the levels from Th5 to L3. Spinal cordectomy was subsequently undertaken and revealed anaplastic glial cells infiltrating diffusely into the spinal cord parenchyma, with prominent subarachnoid spreading and nerve root involvement. Both necrosis and microvascular proliferation were observed. This recurrent tumor was histologically indistinguishable from glioblastoma. Loss of ATRX was noted in the second and third surgical specimens. This is the first histologically proven case of malignant transformation of NF1-associated astrocytoma with ATRX loss during the course.

Abstract Gastric cancer is a heterogenous disease with different phenotypes, genotypes, and clinical outcomes, including sensitivity to treatments and prognoses. Recent medical advances have enabled the classification of this heterogenous disease into several groups and the consequent analysis of their clinicopathological characteristics. Gastric cancer associated with Epstein–Barr virus (EBV) and microsatellite‐unstable tumors are considered to be the two major subtypes as they are clearly defined by well‐established methodologies, such as in situ hybridization and polymerase chain reaction‐based analyses, respectively. However, discrepancies in the histological diagnosis of gastric neoplasms remain problematic, and international harmonization should be performed to improve our understanding of gastric carcinogenesis. We re‐evaluated Japanese cases of early gastric cancer according to the current World Health Organization (WHO) criteria and classified them into genomic subtypes based on microsatellite instability (MSI) and EBV positivity to determine the initial genetic events in gastric carcinogenesis. A total of 113 Japanese early gastric cancers (including low‐ and high‐grade dysplasias) treated with endoscopic resection over 5 years were archived in our hospital. A histological re‐evaluation according to the WHO criteria revealed 54 adenocarcinomas, which were divided into 6 EBV‐positive (11.1%), 7 MSI‐high (MSI‐H, 13.0%), and 41 microsatellite stable cases (75.9%). MSI‐H adenocarcinoma was confirmed by an immunohistochemistry assay of mismatch repair proteins. Programmed death‐ligand 1 immunostaining with two antibodies (E1L3N and SP263) was positive in tumor cells of one MSI‐H adenocarcinoma case (1/7, 14.3%). The proportion of stained cells was higher with clone SP263 than with E1L3N. Histologically, EBV‐positive carcinomas were poorly differentiated (83.8%), and MSI‐H cancers were frequent in well to moderately differentiated adenocarcinoma (85.7%), indicating that the EBV‐positive subtype presented with high‐grade morphology even when an early lesion. Our study indicates that the WHO criteria are useful for subdividing Japanese early gastric cancers, and this subdivision may be useful for comparative analysis of precursor lesions and early carcinoma.

A 68-year-old man with a history of superior mesenteric arterial thromboembolism due to chronic atrial fibrillation had experienced intermittent claudication (IC) of his left leg for 3 years. Computed tomography angiography showed focal occlusive lesions in the left distal popliteal artery and proximal segments of the infrapopliteal arteries. Endarterectomy was performed for these localized arterial lesions, and a drastic symptomatic improvement of IC after revascularization was achieved. The endarterectomized segments remained patent for 4 years after the surgery. Endarterectomy could be a useful alternative to bypass surgery and endovascular therapy for the treatment of localized infragenicular arterial lesions.

Desmoid-type fibromatosis (DF) is a rare, locally infiltrative, and fibroblastic proliferative disease. DF usually arises from abdominal fascial tissue, but in rare cases, it can occur in extra-abdominal areas. A 73-year-old Japanese male complained of a painless, left anterior neck mass of 3-month duration. Computed tomography revealed the mass measured 9 × 7 × 6 cm and extended to the anterior mediastinum, with invasion of the left clavicle. En bloc resection of the tumor with the left sternoclavicular joint and the medial portion of the left clavicle was performed by cervico-thoracic approach with L-shaped partial sternotomy. Histopathologic examination showed fascicular growth of spindle-shaped cells separated by abundant collagen. Immunohistologic examination revealed nuclear staining of β-catenin and cytoplasmic staining of vimentin. Genetic analysis of 160 cancer-related genes by next-generation sequencing (NGS) demonstrated only a missense mutation in the CTNNB1 gene (c.133T>C, p.S45P). DF extending from the neck to the anterior mediastinum is rare. We report the complete resection of a large-sized DF with the clavicular invasion. A low-frequency CTNNB1 mutation of DF was identified. Genetic analysis with NGS was beneficial for the diagnosis.

背景 : Adult granulosa cell tumor (AGCT) は, 全卵巣腫瘍の約 1%を占める低悪性度性索間質性腫瘍で, 長期経過後の再発がよく知られている. 今回, 既往不明で組織診断に苦慮した 17 年後の AGCT 再発症例で, 剖検時の細胞学的所見が確定診断の一助となった 1 例を報告する.

BACKGROUND:Cancer genome profiling of cytology specimens using next-generation sequencing (NGS) requires adequate and good-quality DNA. Genomic examination of cytology samples was conventionally performed on cell block (CB) or smear specimens than on residual liquid-based cytology (LBC) specimens, which are high-quality DNA sources even after long-term storage.METHODS:We estimated tumor fractions of 37 residual LBC specimens, including 30 fine needle aspiration (FNA) samples from the thyroid (12 papillary thyroid carcinomas and two malignant lymphomas), lymph node (13 metastatic carcinomas and one malignant lymphoma), and breast cancer (one phyllodes tumor and one invasive ductal carcinoma), two pancreatic carcinoma samples, and five liquid (ascites, pleural effusion, and cerebrospinal fluid) samples. The DNA was extracted from all samples and subjected to NGS using a customized cancer gene panel comprising 28 cancer-related genes.RESULTS:NGS analysis revealed somatic mutations corresponding to pathological diagnosis with adequate variant allele frequency (VAF) in 24 LBC specimens, which had significantly higher tumor fraction (72.5% ± 4.9%). Ten cases, including the five fluid samples, had very small tumor fractions (7.5% ± 2.3%) to obtain sufficient VAF. Other two samples had high tumor fractions but showed very low VAF, indicating the presence of fusion genes. The remaining one sample yielded no DNA recovery.CONCLUSION:The residual LBC specimens collected by FNA from the thyroid gland and lymph node were verified to carry high tumor fraction and could serve as an alternate source for molecular testing to screen and diagnose cancers without the use of CB or smears.

Rationale: Gastric mixed adenoneuroendocrine carcinoma (gMANEC) is a rare malignant tumor. Most gMANECs are diagnosed at an advanced stage and have a worse prognosis than gastric adenocarcinoma. In order to improve the prognosis, it is necessary to diagnose gMANEC at an early stage. However, the endoscopic features of early gMANECs are unclear. We, herein, report a case of early gMANEC that showed characteristic magnifying endoscopic findings. Patient concerns: A 78-year-old man was referred to our institution for endoscopic resection of a gastric lesion. He had a medical history of distal gastrectomy due to early gastric cancer with negative surgical margins 9 years previously. Diagnosis: Esophagogastroduodenoscopy showed a reddish depressed lesion on the suture line of the gastric remnant, which was classified as type 0-IIc according to the Paris classification. ME-NBI at the oral side of the lesion revealed the absence of the microsurface pattern (MSP) and scattered microvessels with dilation and caliber variation, while ME-NBI at the anal side showed an irregularly tubular MSP. An endoscopic forceps biopsy showed a well- to moderately differentiated adenocarcinoma. Interventions: We performed endoscopic submucosal dissection, anden blocresection of the tumor was successfully achieved. Outcomes: The histological findings showed two distinct components: neuroendocrine carcinoma (NEC) and well-differentiated adenocarcinoma, which comprised similar to 60% and 40% of the tumor, respectively. The NEC component corresponded to the site with the absence of an MSP and scattered microvessels on ME-NBI, while the well-differentiated adenocarcinoma component corresponded to the site with an irregularly tubular MSP. The pathological diagnosis was mixed adenoneuroendocrine carcinoma, infiltrating into the deep submucosal layer. Lessons: We propose that the absence of an MSP plus an irregular MSP is characteristics of gMANEC, which was useful for the diagnosis of gMANEC before treatment.

INTRODUCTION:Familial adenomatous polyposis (FAP) is typically characterized by more than hundred adenomatous polyps in the colorectum, caused by germline APC mutation. A small proportion of the polyps progress to colorectal adenocarcinoma via adenoma-carcinoma sequence. Serrated lesions and polyps, characterized by a serrated architecture of the epithelium, are noted for two types of genetic pathways in colorectal carcinogenesis. BRAF and KRAS mutations are observed in the serrated pathway.CASE REPORT:We report a young FAP patient with rectal serrated adenomas that were removed by colonoscopic procedures. The histological features with villiform projections and slit-like serration indicated traditional serrated adenoma. A genetic examination with next-generation sequencing showed a somatic BRAF mutation in the serrated adenoma and APC mutations in the tubular adenomas. His germline mutation was found at APC p.Q1928fs*.CONCLUSION:Serrated adenomas with dual genetic alterations in a FAP patient may be associated with colorectal carcinogenesis and should be considered a target lesion for treatment. The present study demonstrated the malignant potential of serrated adenoma in a FAP patient.

OBJECTIVE:Intraoperative evaluation of sentinel lymph nodes (SLNs) for patients with breast cancer is widely performed with frozen section (FS), cytology, or a combination of both. Touch imprint cytology (TIC) reportedly has an equivalent sensitivity to FS. We studied its diagnostic utility to detect SLN metastases.MATERIALS AND METHODS:Cases of 367 patients with breast cancer who underwent intraoperative valuation of SLNs (507 LNs) were evaluated. All FS and corresponding TIC slides of SLNs of each case were reviewed microscopically for the presence of metastases of any size. If present, the metastatic focus was measured on the FS.RESULTS:Of these 507 SLNs, 82 LNs (16.2%) from 69 women were found to have metastases in the FS and consisted of 5 LNs of isolated tumor cells, 15 of micrometastasis, and 62 of macrometastasis. TIC identified metastases in 69 of these 82 SLNs (sensitivity: 84.1%, specificity: 100%, and accuracy: 97.4%). All macrometastases could be detected by TIC, whereas TIC identified approximately 50% of micrometastases and none of isolated tumor cells. The size detection limit of metastatic foci, defined as the smallest dimension of metastasis detected without false negatives, was 2 mm. The smallest metastatic focus identified was 0.8 mm.CONCLUSIONS:TIC of SLNs is of great use given its negative predictive value of 100% for identification of macrometastasis in our study. For intraoperative evaluation of SLNs, based on our data, a practical two-step approach is proposed: SLN evaluation should be initially performed by TIC and then proceed to FS histological analysis only when cytologically positive to determine the size of metastatic focus.