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The nuclear lamina protein, Lamin A and inner nuclear membrane protein, emerin participate in maintaining nuclear morphology. However, their correlations with the nuclear shape in the four representative ovarian epithelial cancer subtypes, high-grade serous carcinoma (HGSCa), clear cell carcinoma (CCCa), endometrioid carcinoma (EMCa) and mucinous carcinoma (MUCa), remains unclear. The present study aimed to investigate the association between nuclear morphology and nuclear membrane protein expression in four histological subtypes of ovarian epithelial cancer. A total of 140 surgically resected ovarian cancer specimens were subjected to Feulgen staining to evaluate nuclear morphology, and immunohistochemistry analysis to assess Lamin A and emerin expression. The histological images were analyzed via computer-assisted image analysis (CAIA). The results demonstrated that the mean nuclear area of EMCa was significantly smaller compared with CCCa (P=0.0009). The standard deviation of the mean nuclear area was used to assess nuclear size variation, and the results indicated that EMCa lesions were significantly smaller than CCCa lesions (P=0.0006). Regarding the correlation between the Lamin A-positive rate and nuclear morphological factors, positive correlations were observed with nuclear area in CCCa and EMCa (R=0.2855 and R=0.2858, respectively) and nuclear perimeter in CCCa, EMCa and MUCa (R=0.2409, R=0.4054 and R=0.2370, respectively); however, a negative correlation with nuclear shape factor was observed in HGSCa and EMCa (R=-0.2079 and R=-0.3707, respectively). With regards to the correlation between emerin positivity and nuclear morphological factors, positive correlations were observed with nuclear shape factor in HGSCa (R=0.2673) and nuclear area in CCCa (R=0.3310). It is well-known that HGSCa and CCCa have conspicuous nuclear size variation, and EMCa has small nuclei without strong atypia. These findings were verified in the present study via CAIA. Taken together, the results of the present study suggest that Lamin A strongly contributes to the maintenance of nuclear morphology in ovarian epithelial cancer compared with emerin, although their contributions differ based on tumor subtype., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Watabe et al.)

Carcinomatous meningitis is a condition in which tumor cells spread to the subarachnoid space. Leukocyte counting and typing of cerebrospinal fluid (CSF) cell components are performed manually or using flow cytometry. However, a detailed analysis of these variables using cytological specimens has not yet been reported. The present study analyzed cytological specimens using Giemsa staining and whole slide imaging with computer-assisted image analysis (CAIA) to clarify the characteristics of the leukocyte population in CSF, especially in carcinomatous meningitis. Manual evaluation was performed using 280 Giemsa-stained cytological CSF specimens. For 49 samples, CAIA was used for the whole area of Papanicolaou (Pap) staining, and Giemsa-stained specimens of the same samples were imaged using a virtual slide scanner. The nuclear morphology of the leukocytes was assessed, and the total leukocyte and leukocyte subset (lymphocytes, neutrophils and macrophages) counts were evaluated. Then, the number and percentage of each leukocyte subset population were evaluated. The total leukocyte count was significantly higher in Giemsa-stained specimens compared with in Pap-stained specimens. The percentage of macrophages was significantly higher in samples from patients with non-hematological tumors compared with in samples from patients without tumors, which was confirmed by manual evaluation of the specimens. In addition, the cut-off value of the percentage of macrophages that could discriminate between the tumor history negative cases and cytologically tumor positive cases was determined, revealing that a higher proportion of macrophages reflected the existence of atypical/malignant epithelial tumor cells in CSF samples. Thus, atypical cell screening and analysis of the background characteristics of the leukocyte population should be the focus of cytological specimen screening, especially not to miss carcinomatous meningitis., (Copyright: © Kobayashi et al.)

Second primary malignancy (SPM) is a severe issue for cancer survivors, particularly for osteosarcoma (OS) survivors. To date, the associations between subsequent SPM and OS have been well reported. Hematogenic and solid malignancies tend to occur following OS treatment. Reportedly, 2-[ 18 F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) is mainly used in OS patients for initial cancer staging, to evaluate the response of neoadjuvant chemotherapy, and when recurrence or metastasis is clinically suspected. The present case report describes a 70-year-old man diagnosed with three primary malignancies: jaw OS, myelodysplastic syndrome and colorectal adenocarcinoma. To the best of our knowledge, this combination of malignancies has not been reported previously. Until now, there is no specific protocol of postoperative FDG-PET for OS patients. Few studies have described OS follow-up methods; therefore, there is no consensus on proper follow-up methods. In the present case report, the colorectal early-stage SPM was observed, without any symptoms, by FDG-PET/computed tomography. To avoid overlooking solid SPMs, it is suggested that FDG-PET should be performed in the long-term follow-up of OS patients.

Recent advances in computer technology have been made and image analysis (IA) has been introduced into pathological fields. The present study aimed to investigate the utility of IA for the evaluation of nuclear features and staining of immunohistochemistry (IHC) for Ki-67, p53 and GATA-binding protein 3 (GATA-3) in urothelial carcinoma tissue samples. A total of 49 cases of urothelial carcinoma tissue samples were obtained by transurethral resection of bladder tumors, which included 11 low-grade papillary urothelial carcinomas (LGPUCs), 1 non-invasive high-grade urothelial carcinoma and 37 infiltrating urothelial carcinomas (IUCs). Whole slide imaging (WSI) and IA were performed in Feulgen reaction and IHC-stained tissue samples. There was a significant difference in the average nuclear density, standard deviation (SD) of nuclear size and SD of nuclear minimum and maximum diameter between LGPUC and IUC, which is equivalent to the diagnostic features of IUC in nuclear variability, and hyperchromatic nuclei. In addition, the present study revealed that the SD of nuclear density was significantly different between the two groups. Regarding IA in IHC-stained tissue samples, Ki-67 was significantly overexpressed in IUC. Furthermore, the GATA-3 expression level in IUC samples with muscle invasion was significantly downregulated compared with that in non-muscle invasive tumors. The results of the present study suggest that IA in combination with WSI may be a beneficial tool for evaluating morphometric characteristics and performing semi-quantitative analysis of IHC.

Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare self-limiting disorder typically affecting the cervical lymph nodes (LNs), which is often misdiagnosed as other LN-associated diseases. KFD frequently presents with necrotic lesions and recurrences, which are also features of metastatic LNs. Clinicians may thus suspect LN metastasis when they encounter ipsilateral cervical lymphadenopathy in a patient with head and neck cancer. The present study reports the case of a 48-year-old man with tongue cancer and KFD affecting the right edge of his tongue and ipsilateral cervical LNs. LN metastasis was initially suspected, but pathological examination of the dissected LNs revealed one necrotic metastatic lesion and two necrotic KFD lesions. Ipsilateral cervical lymphadenopathy recurred 6 years after the initial surgery, and it was not possible to differentiate clinically between a second primary tumor and recurrent KFD prior to treatment. To the best of our knowledge, this is the first reported case of simultaneous tongue cancer, regional LN metastasis and KFD. This highlights the requirement to consider KFD in the event of LNs with necrotic lesions but no cancerous cells. A combination of clinical and pathological approaches may aid in the diagnosis of KFD, in addition to ruling out LN metastasis in initial and recurrent lymphadenopathies. The present study indicate that a diagnosis of KFD should be considered in patients with head and neck cancer that exhibit necrotic LNs lacking cancerous cells. This is important, as misdiagnosis of KFD as LN metastasis may lead to unnecessary adjuvant therapy.

In view of the small number of recurrent and metastatic cases of female adnexal tumors of probable Wolffian origin (FATWO), there is a distinct lack of evidence to support recommendations regarding treatment. In the present study, a 37-year-old female was diagnosed with a left adnexal tumor and underwent a left salpingo-oophorectomy (SO). The tumor was found to arise from the left tubal fimbria and extend to the posterior leaf of the broad ligament. Pathological examination identified a number of solid, tubular and cystic architectures, with areas of hyalinization, hemorrhage and necrosis. Immunohistochemistry detected that the tumor cells were positive for cytokeratin (CK)7, vimentin, inhibin and calretinin, and negative for CK20, epithelial membrane antigen, and the estrogen and progesterone receptors. Thus, the patient was diagnosed with FATWO. Following 15 months, the patient developed recurrent tumors and subsequently underwent a total abdominal hysterectomy, a right SO and extirpation of the disseminated tumors, but with incomplete debulking. The tumor cells were immunoreactive for KIT. As there are a limited number of treatment options and few reported cases, limiting the therapy recommendations, imatinib mesylate was administered for 6 months and the tumors were temporarily stabilized for 4 months until the disease progressed. The patient underwent a further debulking surgery that did not achieve complete debulking and was subsequently administered a combination chemotherapy of paclitaxel and carboplatin. This regimen resulted in an almost complete response after 10 cycles. The tumors continued to decrease in size, and the tumors in the left side of the Douglas pouch and the right para-colic gutter were no longer detectable. To the best of our knowledge, the current study is the first to report carboplatin and paclitaxel combination therapy demonstrating a response of this degree to recurrent FATWO following the failure of imatinib treatment. However, surgical debulking remains the most effective treatment for FATWO when is it is possible. The precise role of chemotherapy, radiotherapy and molecular-targeting therapy in the treatment of recurrent or metastatic FATWO remains to be elucidated, and therefore, novel strategies to overcome this disease must be prioritized.