Yoji Kukita

Introduction: DEK::AFF2 fusion-associated papillary squamous cell carcinoma is a recently characterized sinonasal neoplasm that closely mimics Schneiderian papilloma. Although one report has described fine-needle aspiration cytology of a metastatic lymph node, scrape cytological features from the primary site remain undocumented. Case Presentation: We report the scrape cytology of this tumor in a 26-year-old woman. While certain features (perivascular arrangement and intracytoplasmic nuclear debris-like structures) overlapped with Schneiderian papilloma, several findings diverged: a predominantly discohesive pattern, nuclear enlargement with anisonucleosis, prominent nucleoli, stippled chromatin distinct from the neuroendocrine pattern, and a crackled cytoplasmic appearance. Immunohistochemistry for synaptophysin and chromogranin A was negative, excluding neuroendocrine differentiation. CD163 immunohistochemistry confirmed that the debris-containing cells were not histiocytes. E-cadherin showed heterogeneous downregulation in the initial biopsy, suggesting a candidate molecular basis for the discohesive pattern. The diagnosis was confirmed by AFF2 immunohistochemistry, DEK break-apart fluorescence in situ hybridization, and reverse transcription polymerase chain reaction with Sanger sequencing. Retrospective AFF2 immunohistochemistry of the initial biopsy, originally diagnosed as Schneiderian papilloma, was positive. The patient remained free of disease progression 34 months after completion of chemoradiotherapy for the antecedent lacrimal sac carcinoma. Conclusion: These findings provide the first comprehensive cytological documentation of this entity from a primary sinonasal site and delineate features diverging from Schneiderian papilloma that may prompt ancillary investigations.

Aims: The nosology of primary cutaneous apocrine carcinoma remains controversial, as the term has often been used as a heterogeneous diagnostic category. The aim of this study was to clarify the clinicopathological and molecular features of strictly defined apocrine carcinoma using modified diagnostic criteria. Methods and results: Thirty cases were collected from three institutions. Male predominance (28/30, 93%), predominance in elderly patients (median age, 72 years; range, 33–89 years) and the favourite site of the axilla (29/30, 97%) were observed. Lymph node and distant metastases occurred in 64% (16/25) and 28% (7/25) of cases, respectively. Two patients died of the disease (2/25, 8%), with a median follow‐up period of 2 years and 1 month. Histopathologically, all tumours harboured cytoplasmic zymogen‐like granules; however, some (8/30, 27%) lacked apocrine secretion features. Nucleoli were either moderately prominent ( n = 17) or prominent ( n = 13). Apocrine gland hyperplasia was identified in 5 (17%) of the 30 cases. Immunoexpression of androgen receptor, BerEP4, cytokeratin 7, GATA3 and GCDFP15 was observed in all tested cases. In contrast, BCL2, CEA, oestrogen receptor and progesterone receptors were negative in all tested cases. Only 13 cases underwent molecular studies. PIK3CA hotspot mutations were detected in 8 of the 13 cases. Panel sequencing revealed KMT2D ( MLL2/4 ) mutations in three cases, all of which have no PIK3CA mutations. Conclusions: Primary cutaneous apocrine carcinoma is a distinct entity characterized by remarkably consistent clinical, cytopathological, immunohistochemical and molecular features.

Accurate detection of gene fusions is critical for the diagnosis of bone and soft tissue tumors, yet conventional gene panel testing remains costly and impractical when processing small sample numbers. Here, we present a cost‐effective and scalable in‐house workflow using a custom capture panel combined with nanopore sequencing and TEQUILA‐based probe synthesis. We analyzed 24 sarcoma samples with known gene fusions, comprising frozen and formalin‐fixed paraffin‐embedded (FFPE) specimens. Expected fusions were detected in all 7 frozen samples and in 16 of 17 FFPE samples. Long‐read sequencing enabled direct characterization of full‐length fusion transcripts, providing structural information beyond fusion junctions. Gene expression quantification showed strong concordance with short‐read sequencing (Spearman r = 0.770–0.976), supporting quantitative reliability. Down‐sampling analysis demonstrated that 100–200 Mb of sequencing data per sample was sufficient for reliable fusion detection, while deeper sequencing improved sensitivity for lowly expressed fusions. In addition, reuse of flow cells supported flexible and efficient sequencing for small sample batches. This approach provides a practical and extensible framework for in‐house fusion detection and improves the accessibility of molecular diagnostics for rare cancers.

The classification of inverted follicular keratosis (IFK) remains controversial, with debate on whether it represents a variant of seborrheic keratosis, a follicular poroma (folliculosebaceous poroma), or a distinct tumor type. To clarify, we conducted genetic analyses to detect FGFR3 and PIK3CA mutations, as well as PAK1/2/3 rearrangements, in IFK cases. IFK was diagnosed based on exo‐endophytic or endophytic growth; biphasic basaloid and squamoid keratinocytes with acantholysis and squamous eddies; and absence of adnexal differentiation. Using these histopathological criteria, 12 IFK cases were identified in our two hospitals. The cohort comprised 10 male and 2 female patients, with a median age of 59.5 years (range: 42–89). Most tumors were located on the face ( n = 11, 92%) and were small in size (median: 6.5 mm; range: 2–13 mm). No cases demonstrated local recurrence or metastasis. Histologically, tumor architecture was classified into three patterns: papillomatous wart‐like ( n = 5), keratoacanthoma‐like ( n = 3), and solid nodular ( n = 4). Sanger sequencing revealed the presence of FGFR3 p.R248C ( n = 1/10, 10%), PIK3CA p.E545K ( n = 1/10, 10%), and PIK3CA p.H1047Y ( n = 1/10, 10%), although analysis failed in the two oldest cases owing to degraded DNA. PAK1/2/3 break‐apart fluorescence in situ hybridization (FISH) showed no split signals in any case; PAK3 FISH also failed in the same two older specimens. Thus, IFK may represent a distinct clinicopathologic variant of seborrheic keratosis under our proposed diagnostic criteria.

Aims: Apocrine carcinoma ( AC ) is a rare and distinct subtype of invasive breast carcinoma, typically characterized by androgen receptor ( AR ) positivity and negative expression of oestrogen and progesterone receptors. This study aimed to clarify the metabolic and molecular characteristics of AC , with a particular focus on protein expression related to lipid metabolism and the frequency and nature of PIK3CA mutations. Methods: We analysed tissue specimens from 40 cases with AC and 59 cases with other breast cancer subtypes ( ER +/ HER2 −, ER +/ HER2 +, ER −/ HER2 + and triple‐negative breast cancer [ TNBC ]). Immunohistochemistry was performed for a panel of lipid metabolism‐related proteins including FASN , AMACR , ACOX1 , ACSL1 and catalase. mRNA Expression of ACSL1 was assessed by RT ‐ qPCR and PIK3CA mutations were analysed via targeted sequencing. Results: AC showed significantly higher expression of enzymes involved in fatty acid synthesis and peroxisomal β‐oxidation compared to other subtypes. Notably, ACSL1 was upregulated at both protein and mRNA levels, and catalase was upregulated at the protein level, indicating an increase in peroxisomes. PIK3CA Mutations, particularly the hotspot p. H1047R variant, were detected at a significantly higher frequency in AC (68.4%) compared to the other subtypes: ER +/ HER2 − (52.6%), ER +/ HER2 + (27.3%), ER −/ HER2 + (50.0%) and TNBC (33.3%) ( P < 0.05). Conclusions: AC is characterized by distinct metabolic reprogramming, with preferential upregulation of peroxisomal β‐oxidation rather than mitochondrial pathways. These metabolic features are accompanied by a high prevalence of activating PIK3CA mutations, suggesting a link between genomic alterations and metabolic phenotype. These findings provide new insights into the pathobiology of AC and may assist in its histopathological differentiation from other breast cancer subtypes.