Yoshifumi Iwahashi

Clinicopathological significance of podocalyxin and phosphorylated ezrin in uterine endometrioid adenocarcinoma

Background Podocalyxin is an anti-adhesive glycoprotein that has been associated with highly aggressive forms of cancers. Podocalyxin increases the migration and invasive properties of cancer cells through its interaction with ezrin, which undergoes an increase in phosphorylation through podocalyxin. Aims To study the roles of podocalyxin and phosphorylated ezrin (pEzrin) in uterine endometrioid adenocarcinoma (UEA). Methods Using immunohistochemisty the authors investigated the expression of podocalyxin and pEzrin along with some well-known markers of tumour aggressiveness including p53, oestrogen receptor and Ki-67 in UEA. Results Podocalyxin and pEzrin expression levels were positive in 36.1% (22 of 61 patients) and 50.8% (31 of 61 patients) of UEA cases, respectively. Further, podocalyxin expression was correlated with tumour grade (p=0.0001), FIGO stage (p=0.0062), p53 expression (p=0.0050) and Ki-67 index (p=0.0069). In addition, pEzrin expression was associated with FIGO stage (p=0.0231), p53 expression (p<0.0001) and Ki-67 index (p=0.0010). The expression of podocalyxin was also correlated with that of pEzrin (p=0.0102). Conclusions These results suggest that overexpression of podocalyxin and pEzrin may indicate a more aggressive phenotype; thus, evaluation of these proteins may be useful in prediction of disease progression in UEA cases.

Tumor budding is an independent risk factor for lymph node metastasis in cutaneous squamous cell carcinoma: a single center retrospective study.

Although tumor budding is acknowledged as a risk factor for lymph node metastasis in certain types of carcinoma, it is not well investigated in cutaneous squamous cell carcinomas (SCCs). In this study, we analyzed the correlation between tumor budding and nodal metastasis in cutaneous SCC.

Monoclonality of composite large-cell neuroendocrine carcinoma and invasive intestinal-type mucinous adenocarcinoma of the cervix: a case study.

A rare case of mixed carcinoma of the cervix is reported, composed of a large-cell neuroendocrine carcinoma and an invasive intestinal-type mucinous adenocarcinoma. The large-cell neuroendocrine carcinoma was composed of solid nests, sheets, and trabeculae of medium-sized to large-sized cells, and was positive for chromogranin-A and CD56. The invasive intestinal-type mucinous adenocarcinoma showed sparsely scattered immunoreactivity for chromogranin-A. Using an X-chromosome clonality assay, these 2 components showed patterns of monoclonality. These results suggest that the large-cell neuroendocrine carcinoma may have arisen from the invasive mucinous adenocarcinoma.

Case report of aquagenic wrinkling of the palms associated with impaired stratum corneum function.

Dear Editor, Aquagenic wrinkling of the palms (AWP) is an uncommon disease characterized by the rapid formation of transient edematous and whitish plaques on the palms after exposure to water. AWP usually occurs in young females with family history, and thus heredity may be related. Although the pathophysiology of AWP remains unknown, aberrant sweat glands and alterations of the stratum corneum are thought to be involved. Herein, we report a case of AWP in which histological and functional studies were carried out.

Adipophilin expression in cutaneous malignant melanoma

The lipogenic pathway is upregulated in cancer cells, including melanomas. However, the pathological significance of cellular lipids in melanocytic lesions has yet to be determined. In this study, we evaluated intracytoplasmic lipid droplets in melanocytic nevi (MNs) and malignant melanomas via immunohistochemical analysis of adipophilin (ADP), which coats lipid droplets.

Macrocystic ductal adenocarcinoma of prostate: A rare gross appearance of prostate cancer

Macroscopic cyst-formation by prostatic adenocarcinoma, herein referred to as macrocystic prostatic adenocarcinoma (MPA), is extremely rare. To date, no studies of prostate cancer performed based on gross cystic appearance have been reported. MPA can include various diseases, one of which is cystadenocarcinoma. Several cases of ductal adenocarcinoma exhibiting a macrocystic appearance have recently been reported; however, the histological and clinicopathological characteristics of MPAs have yet to be characterized and established. Therefore, we aimed to determine the histological and clinicopathological characteristics of MPA, via a multi-institutional investigation. We discovered five patients with MPA out of 1559 treated patients (0.32%); all cases were ductal adenocarcinomas. MPA was found to have three growth patterns: Two cases showed a prevalence of exuberant papillary proliferation with a fibrovascular core in the macroscopic multilocular cysts. Two others predominantly exhibited multilocular cysts lined by flat epithelium with foci of low papillae, and the fifth had a cystic lesion with intracancerous necrosis. Three of the cases showed extraprostatic invasion; however, none of the patients experienced recurrence during the follow-up period. Each predominant growth pattern tended to exhibit unique clinicopathological characteristics with respect to serum prostate specific antigen level and tumor size and location. In conclusion, we demonstrated that MPA is a ductal adenocarcinoma that is composed of intracystic exuberant papillary proliferation and flat proliferation with foci of low papillae, both of which might exhibit different clinicopathololgical appearances.

2016 measles outbreak in Japan: A report of two cases with reappraisal of histological features

Dear Editor, Measles is a highly contagious airborne viral disease causing more than 100 000 deaths per year worldwide. Although measles is a rare disease in developed countries including Japan, a measles outbreak at the Kansai International Airport occurred in 2016, infecting 33 people in total. Herein, we describe two of these patients who were working at the airport with a focus on their pathological findings. Case 1 was a Japanese woman in her 20s who was nonimmunized for measles. On the day of onset, she consulted a local doctor and was prescribed acetaminophen, dextromethorphan, loxoprofen and cefcapene for her fever and headache. On the next day, multiple erythematous skin papules developed on her face, gradually spreading all over her body (Fig. 1a). She consulted our hospital 8 days after onset. On admission, erosions of the cornea and lip were observed in addition to systemic erythema. Laboratory studies revealed positivity for measles immunoglobulin M and reverse transcription polymerase chain reaction (RT–PCR) test from a pharyngeal swab specimen. Results of drug lymphocyte stimulation tests were all negative. Case 2 was a Japanese man in his 30s who was also non-immunized for measles. His clinical history and cutaneous presentation was similar to case 1 (Fig. 1d). Again, he was diagnosed with measles by RT–PCR test. Both patients recovered with rest and an i.v. infusion only. Because of its rarity, diagnosis of measles is challenging in developed countries and its histological findings are underrecognized. In present cases, drug eruption was a serious diagnostic concern and we performed skin biopsies. Histologically, both cases presented vacuolar type interface dermatitis with dyskeratotic keratinocytes, and differentiation from viral infection did not seem possible at first. In retrospective glass slide review, however, we noticed that multinucleated keratinocytes existed in the hair follicles of both patients (Fig. 1b,c,e,f), which has been previously documented in measles infection. In case 1, multinucleated keratinocytes were also found in the epidermis. Subsequently, we reviewed 30 cases of skin biopsies previously diagnosed as a drug eruption, but no follicular multinucleated keratinocytes were observed in any of the cases reviewed. Measles virus is an RNA virus of the genus Morbillivirus within the paramyxovirus family. Fusion protein expressed by paramyxovirus-infected cells further leads to the merger of the cells resulting in multinucleated infected cells. In addition, the measles virus is a folliculotropic virus that often infects the follicular epidermis. Therefore, it is reasonable to find multinucleated keratinocytes in a hair follicle biopsied from the skin rash of measles patients. It should be noted that multinucleated keratinocytes are also seen in other viral diseases, such as the herpes simplex virus (HSV) and varicella zoster virus (VZV). Compared with measles, however, multinucleated keratinocytes seen in HSV/ VZV are larger, with molding of ground glass nuclei and marginated chromatin. Additionally, several non-infectious inflammatory dermatoses can also have multinucleated keratinocytes but are usually not observed in drug eruption. In summary, follicular multinucleated keratinocytes are a valuable pathological clue to differentiate measles from a drug eruption which would aid the early diagnosis and prevent spreading.

HER2 is frequently overexpressed in hepatoid adenocarcinoma and gastric carcinoma with enteroblastic differentiation: a comparison of 35 cases to 334 gastric carcinomas of other histological types

Aims α-Fetoprotein (AFP)-producing gastric carcinoma (AFPGC) is one of the most aggressive GC subtypes. Frequent expression of human epidermal growth factor receptor 2 (HER2) has previously been reported in hepatoid adenocarcinoma (HAC), a major histological subtype of AFPGC originating from common-type GC (CGC). However, HER2 expression levels in other AFPGC histological subtypes are unknown. In this study, we analysed HER2 expression in GCs with primitive phenotypes in addition to HAC. Methods HER2 expression was evaluated in representative complete sections from 16 HACs, 19 GCs with enteroblastic differentiation (GCEDs) and 334 GCs of other histological types as controls. The Ruschoff/Hofmann method was used to score HER2 immunohistochemistry. Samples with a HER2 score of 2+ were further assessed using fluorescence in situ hybridisation. Oncofetal protein (OFP) expression in HAC and GCED was tested via immunohistochemical staining for AFP, glypican 3 and Sal-like protein 4. Results Thirty of 35 HAC/GCED cases comprised more than two histological patterns. The HER2 positivity rates of each histological component in the HACs/GCEDs were 25.0% for HAC (n=16), 34.6% for GCED (n=26) and 48.1% for CGC (n=27), which were higher than those of the control group (13.8%). Additionally, the majority of CGC components in HACs/GCEDs were positive for OFP (88.9%). Conclusions HER2 is frequently overexpressed not only in HAC but also in GCED and CGC components of HACs/GCEDs, which suggests an association between HER2 and OFP expression. Moreover, our findings suggest that HER2-positive CGC has a higher risk of progression to HAC/GCED than HER2-negative GC.

Novel Application of Loop-mediated Isothermal Amplification for Rapid Detection of Gene Translocation

Identification of fusion genes in cancer is essential for pathological diagnosis and clinical therapy. Although methods for detection of fusion genes, such as fluorescence in situ hybridization (FISH) and real-time polymerase chain reaction (PCR), have been developed in last two decades, these methods are not ideal for detection of these genetic alterations owing to their high cost and time-consuming procedures. In this study, we developed novel application for detection of gene translocations using loop-mediated isothermal amplification (LAMP). We verified the amplified DNA products of echinoderm microtubule-associated protein-like 4 and anaplastic lymphoma kinase (EML4-ALK), synaptotagmin and synovial sarcoma, X breakpoint (SYT-SSX), and immunoglobulin heavy chain gene and B cell leukemia/lymphoma 2 (IgH/BCL2) by real-time PCR, agarose-gel electrophoresis, and the naked eye after the LAMP procedure. Fusion genes were detected in samples diluted 103 times within 60 min. Because of the advantages of rapid amplification, simple operation, and easy detection without requiring sophisticated equipment or technical skill, LAMP may have potential applications as an on-site analytical approach in hospitals for pathological diagnosis and decision making regarding appropriate therapeutic approachs.

A case of rheumatoid vasculitis with acquired reactive perforating collagenosis

Abstract A 55-year-old man with rheumatoid arthritis (RA) presented hyperkeratotic erythematous papules with crusts or blisters on his limbs and buttocks. A histological study showed acquired reactive perforating collagenosis. Soon, skin lesions changed to umbilicated lesions with black necrosis, and the scar from his skin biopsy ulcerated with induration due to rheumatoid vasculitis. Systemic corticosteroids and tacrolimus administration resolved the RA and skin lesions. Rheumatoid vasculitis with acquired reactive perforating collagenosis has not been reported previously.