Histology of Bronchiolar Tumor Spread Through Air Spaces.

The clinical significance of lung tumor spread through air spaces (STAS) has been extensively studied, and is recognized as a unique pattern of invasion. Previous studies of STAS have focused primarily on STAS in alveolar spaces, whereas STAS in the bronchiolar spaces (bronchiolar STAS) has been described in only a few case reports only. Here, we examined 306 cases of primary lung adenocarcinoma and found that bronchiolar STAS was present in 18%. Bronchiolar STAS was associated with an inferior prognosis, more advanced stage, and higher histologic grade. No significant difference in clinicopathological factors or prognosis was observed between cases with bronchiolar STAS and those with alveolar STAS alone. Notably, bronchiolar STAS often occurred simultaneously with alveolar STAS and endobronchial spread of adenocarcinoma, particularly when bronchiolar STAS was present outside the main tumor. We also identified cases where bronchiolar STAS and endobronchial spread of adenocarcinoma occurred simultaneously in the same bronchi or bronchioles located outside the main tumor, as well as cases with bronchiolar STAS adjacent to intrapulmonary metastatic nodules. Our results highlight the significant role of bronchiolar STAS in the aerogenous spread of adenocarcinoma cells. Bronchiolar STAS can be regarded as a histologic variant of alveolar STAS. This study also supports the idea that STAS is not a tissue processing artifact, but a true biological process with clinical implications, offering histologic evidence of aerogenous spread in lung adenocarcinoma.

Endobronchial spread of adenocarcinoma is a distinct pattern of invasion and associated with inferior clinical outcomes in lung adenocarcinoma.

AIM: The spread of lung adenocarcinoma cells into the bronchi and bronchioles is not well documented. We termed this histological finding "endobronchial spreading of adenocarcinoma" (EBSA) and investigated its prevalence and clinical significance. METHODS AND RESULTS: We reviewed 320 resected specimens from patients diagnosed with invasive adenocarcinoma, and EBSA was observed in 144 patients (45%). EBSA was significantly associated with advanced pathological stage, higher histological grade, larger tumour invasion, lymphovascular infiltration, and spread through air spaces. Patients with EBSA had significantly shorter relapse-free survival (RFS) and cancer-specific survival (CSS) in univariate analysis (P < 0.001). In a subgroup analysis of patient with small-sized (invasion size ≤30 mm) adenocarcinoma in the localized stage, EBSA was an independent inferior prognostic indicator in multivariate analysis. In a subgroup analysis of patients with small-sized Grade 1 nonmucinous adenocarcinoma (n = 61), EBSA was observed in 11 patients, and the presence of EBSA was associated with significantly shorter RFS and CSS (P = 0.026 and P = 0.001, respectively). CONCLUSION: Our results demonstrated that EBSA is a significant risk factor for disease recurrence and cancer-related deaths. EBSA can be regarded as a distinctive pattern of invasion and its recognition can be beneficial in the diagnosis of lung adenocarcinoma.

PTEN loss in intraductal carcinoma of the prostate has low incidence in Japanese patients.

Clinical and genomic features of prostate cancer (PCa) vary considerably between Asian and Western populations. PTEN loss is the most frequent abnormality in intraductal carcinoma of the prostate (IDC-P) in Western populations. However, its prevalence and significance in Asian populations have not yet been well studied. In the present study, we evaluated PTEN expression in IDC-P in a Japanese population and its association with ERG expression. This study included 45 and 59 patients with PCa with and without IDC-P, respectively, who underwent radical prostatectomy. PTEN loss was observed in 10 patients with PCa with IDC-P (22%) and nine patients with PCa without IDC-P (17%). ERG expression was relatively frequent in patients with PCa with PTEN loss, although a significant difference was not observed. The co-occurrence of PTEN loss and ERG expression was observed in four patients with PCa with IDC-P and one without IDC-P. PTEN loss and ERG expression did not affect progression-free survival, regardless of the presence of IDC-P. The frequency of PTEN loss in IDC-P is lower in Asian patients than in Western patients. Our results indicate that mechanisms underlying IDC-P in Asian populations are different from those of Western populations.

Adenocarcinoma arising in branchioma with a KRAS and TP53 mutation.

Branchioma is a rare benign neoplasm occurring in the lower neck. Occurrence of malignant neoplasms arising in branchioma is extremely rare. Here, we report a case of adenocarcinoma arising in branchioma. A 62-year-old man had a right supraclavicular mass measuring 7.5 cm in diameter. The tumor contained an adenocarcinoma component encapsulated in a benign branchioma component. The adenocarcinoma component consisted of high- and low-grade components, with the former accounting for 80% of the adenocarcinoma. The high-grade component was immunohistochemically characterized by diffuse strong p53 expression, while the low-grade component and branchioma component were negative for p53. Targeted sequencing analysis for the branchioma and adenocarcinoma components revealed that the adenocarcinoma component harbored pathogenic mutations in KRAS and TP53. No definitive oncogenic drivers were detected in the branchioma component. Based on these immunohistochemical and molecular findings, we suggest that the KRAS mutation contributed to the pathogenesis of the adenocarcinoma, and the TP53 mutation played a key role in the transition from low-grade to high-grade adenocarcinoma.

Enhanced PD-L1 expression on tumor cells in primary CD30-positive cutaneous large T-cell lymphoma: a report of lymph node lesions of four cases.

Scarce data are available regarding neoplastic PD-L1 (nPD-L1, clone SP142) expression in cutaneous T-cell lymphoma. We recently documented a possible association of increased nPD-L1 expression with tumor progression to secondary nodal involvement in two cases of CD30-positive primary cutaneous large T-cell lymphoma (PC-LTCL) (Pathol Int 2020;70:804). Notably, the nodal sites exhibited classic Hodgkin lymphoma (CHL) mimicry related to both morphology and tumor microenvironment (TME), i.e., abundant PD-L1-positive tumor-associated macrophages and low-level PD-1 expression on T-cells. Immunohistochemistry highlighted distinctly different nPD-L1 positivity between the cutaneous and nodal lesions. In the present study, we aimed to validate this unique phenomenon in a larger series of four cases with FISH and targeted-capture sequencing (targeted-seq) analysis. We retrospectively identified two more cases of CD30-positive PC-LTCL with secondary nodal involvement among all patients consecutively diagnosed between 2001-2021. All cases immunohistochemically exhibited elevated nPD-L1 expression on ≥50% of lymphoma cells in nodal tumors, clearly contrasting with the scarce nPD-L1 positivity (≤1%) in cutaneous tumors. Moreover, all nodal lesions exhibited CHL-like TME, with abundant PD-L1-positive tumor-associated macrophages and low-level PD-1 expression on T cells, although the CHL-like morphology was limited in the two original cases. None showed CD274/PD-L1 copy number alteration by FISH analysis, or structural variations of PD-L1 3'-UTR by targeted-seq analysis. These findings indicated that nPD-L1 expression is linked with tumor progression and CHL-like TME in nodal involvement of PC-LTCL. Interestingly, one autopsied case exhibited heterogeneity of nPD-L1 expression at different disease sites.

Pure ductal adenocarcinoma of the prostate protruding into the prostatic urethra: A case report of MRI findings and literature review.

Ductal adenocarcinoma of the prostate (DCa) is the histological variant of prostatic carcinoma. The macroscopic finding of DCa arising from primary duct by urethroscopy is papillary excrescences in the prostatic urethra. But the finding of MRI remains poorly understood, since there is no coherent report on the MRI finding of DCa arising from primary duct. We herein report a case of DCa arising from primary duct and forming papillary excrescences in the prostatic urethra. The patient was a male in his 70s and presented with gross hematuria a few days ago. Blood test showed elevated prostate specific antigen (PSA). Prostate MRI was performed. There were two lesions in the prostatic urethra and the right transition zone (TZ). On T 2-weighted image (T2WI), the lesion in the prostatic urethra was identifiable, but the lesion in the right TZ was difficult to identify. On diffusion-weighted image (DWI), both lesions showed hyperintense signal and could be identified, and there was continuity between them. Urethroscopy was performed, there was the lesion with papillary excrescences developing from the right dorsal side of prostatic urethra. Transurethral resection of the prostate was performed. The pathological diagnosis was DCa (pure type). A review of previous literature showed that DCa had a slightly hypointense signal on T2WI. It may be difficult to identify DCa in the TZ because DCa and the TZ show similar signals on T2WI. DWI may be useful to accurately assess DCa arising from primary duct.

Cytokeratin 5/6 expression in pT1 bladder cancer predicts intravesical recurrence in patients treated with bacillus Calmette-Guérin instillation.

Bacillus Calmette-Guérin (BCG) instillation is the gold standard for the treatment of patients with pT1 bladder cancer but causes severe adverse effects. Few predictive factors have been established for intravesical recurrence and/or stage progression in bladder cancer. We analysed 138 patients who underwent transurethral resection of bladder tumour and were pathologically confirmed to have stage pT1 bladder cancer. Of these, 72 patients (52.2%) received intravesical BCG instillation, 12 patients (8.7%) demonstrated stage progression, and five patients (3.6%) died of the disease. The number of patients who received BCG instillation was more in the group with multifocal tumours than that in the group with unifocal tumours (p=0.0034). Among 53 patients (38.4%) who demonstrated cytokeratin 5/6 (CK5/6) expression, 15 patients (28.3%) showed CK5/6 expression in more than 10% of tumour cells and 38 patients (71.7%) showed CK5/6 expression in 1-10% of tumour cells. CK5/6 expression was observed in both invasive and non-invasive components in 15 patients (28.3%), only in invasive components in 30 patients (56.6%), and only in non-invasive components in eight patients (15.1%). Furthermore, CK5/6 expression was observed in tumour cells only in front of the invasive component and stroma in 24 patients. The proportion of CK5/6-expressing tumour cells in the invasive component was significantly higher than that in the non-invasive component (p<0.001). The follow-up period for patients who received BCG tended to be shorter than that in the non-BCG patients. The CK5/6-positive group displayed significantly shorter recurrence-free survival (RFS) than the CK5/6-negative group (p=0.0412). Importantly, CK5/6 expression was a significant predictive factor of inferior RFS in the BCG instillation group (p=0.0197). In contrast, CK5/6 expression was not significantly associated with RFS in the non-BCG instillation group (p=0.841). Thus, CK5/6 expression can be a predictive marker for RFS in patients with pT1 bladder cancer and can provide critical information for patient care.

Bronchial carcinoid tumor managed with bronchial artery embolization before endobronchial resection: A case report.

Endobronchial resection using a bronchoscope is often selected as treatment for carcinoid tumors located in the central airways. However, massive bleeding is one of the most serious complications during bronchoscopic surgery. Here, we report the case of a 77-year-old female with a typical carcinoid tumor located in the right truncus intermedius who underwent bronchial artery embolization (BAE) one day before endobronchial intervention using a flexible bronchoscope. The tumor was successfully resected without bleeding. BAE prior to endobronchial resection of carcinoid tumors may be useful for reducing the risk of bleeding.

Clinicopathologic analysis of malignant or premalignant cutaneous neoplasms in Japanese kidney transplant recipients.

It is well known that recipients of kidney transplants are at an increased risk of developing malignant or premalignant cutaneous neoplasms (MPCNs) after transplantation. However, the pathogenesis of MPCNs after kidney transplant has not been well-studied in Asian populations. This study aimed to describe the clinicopathologiccharacteristics of MPCNs in an Asian population. We retrospectively reviewed the medical records of 1956 patients who received kidney transplants at two hospitals in Japan, between 2003 and 2019. Among these patients, 24 developed 50 MPCN lesions, including 14 squamous cell carcinoma (SCC, 28%), 23 Bowen's disease (BD, 46%), 11 actinic keratosis (AK, 22%), and two basal cell carcinoma (BCC, 4%). No patient had malignant melanoma. The duration from transplantation to the diagnosis was significantly longer for SCC than for BD or AK (P=0.021, 0.036, respectively). Seven patients had multiple MPCNs in sun-exposed areas of skin. Among the 50 MPCNs, 40 (80%) were located in sun-exposed areas, and 10 (20%) were located in sun-protected areas. MPCNs in sun-exposed skin were frequently accompanied by dermal solar elastosis (90%, 36/40). We found high-risk human papillomavirus (HR-HPV) infections in two anogenital lesions (100%, 2/2). In contrast, HR-HPV infections were not detected in any extragenital lesions (0%, 0/30). Our results suggested that, among Japanese recipients of kidney transplant, MPCNs in sun-exposed skin areas may be associated with immunosuppression and ultraviolet exposure.

Pathological and Virological Studies of p16-Positive Oropharyngeal Carcinoma with a Good Response to Neoadjuvant Chemotherapy.

Human papillomavirus (HPV)-related, p16-positive oropharyngeal carcinoma is considered to be sensitive to anticancer drugs, and the standard treatment is therefore chemoradiotherapy, rather than surgery, especially for aggressive disease. However, with this higher sensitivity, chemotherapy alone may achieve a pathological complete response (CR), making radiation therapy unnecessary. A 46-year-old man with p16-positive squamous cell carcinoma (SCC) of the lateral oropharynx (palatine tonsil) underwent neoadjuvant chemotherapy. This achieved clinically significant tumor shrinkage and therefore surgery was performed for subsequent definitive treatment. Clinical and CT findings indicated a good effect of neoadjuvant chemotherapy on the tumor. A biopsy prior to chemotherapy revealed SCC, which demonstrated p16 immunoreactivity and positive signals for high-risk HPV by RNA in situ hybridization. The post-chemotherapy surgical specimen showed pathological CR and no p16 positive cells nor positive signals for high-risk HPV those were detected in the pre-chemotherapy specimen. There are some reports of chemotherapy alone achieving pathological CR in cases of p16-positive oropharyngeal carcinoma, but none have included high-risk HPV RNA findings. This is the first report of the disappearance of cancer cells as well as p16 staining and a positive signal for high-risk HPV. Achieving pathological CR confirmed by immunohistochemistry and high-risk HPV RNA in situ hybridization in a solid tumor with chemotherapy alone suggests that chemotherapy may have both an antitumor effect and an antiviral effect. Forgoing subsequent radiotherapy and undergoing surgery might be unnecessary and follow-up instead might be sufficient in such cases. Into the future, in an optimal tailored treatment approach, the option of neoadjuvant chemotherapy should be considered for management of p16-positive oropharyngeal carcinoma. Other options such as tumor immunotherapy are also expected to be effective.

Gender difference in factors affecting the medial longitudinal arch height of the foot in healthy young adults.

[Purpose] Medial longitudinal arch (MLA) height is associated with various injuries and diseases and gender differences, if any. This study aimed to examine factors affecting the MLA height associated with gender differences in healthy subjects with no orthopedic disorders. [Subjects and Methods] This study included 36 healthy adults (19 males, 17 females; mean age, 21.8 ± 3.6 years; body mass index, 21.1 ± 2.0 kg/m2). Their height, body weight, foot length, muscle strength of the tibialis posterior muscle (TPM), toe-gripping strength, hallux valgus angle, inversion microdactylia angle, angle of leg-heel alignment, femoro-tibial angle, and navicular height were measured. Correlation between the ratio of arch height and other measurement parameters was examined. [Results] In females, the ratio of arch height was significantly positively correlated with muscle strength of the TPM and toe-gripping strength and negatively correlated with the hallux valgus angle and the leg-heel alignment, whereas in males, only a positive correlation between the ratio of arch height and muscle strength of the TPM was observed. [Conclusion] These results reveal that etiological mechanisms determining MLA height are different between males and females. Overall, the present results indicate that further studies identifying causes of MLA height variation must include gender-based analysis.