Basaloid squamous cell carcinoma with adenoid cystic-like features of the head and neck region: A report of two cases.

The histology of basaloid squamous cell carcinoma (BSCC) can resemble that of adenoid cystic carcinoma (AdCC). Herein, we report two cases of BSCC with adenoid cystic-like features (BSCC-AdC). We collected cases of AdCC and BSCC of the head and neck region, extracted two cases with unusual histology, and reexamined them histologically and immunohistochemically. Case 1 involved an 81-year-old Japanese male, who had an elastic-hard mass on the left side of his tongue, and a biopsy examination suggested AdCC. Case 2 involved a 63-year-old Japanese male, who had a polypoid mass on his right hypopharynx. He was diagnosed with AdCC with high-grade transformation. Histologically, atypical cells in a myxoid stroma, which exhibited trabecular, nest-like, and/or cribriform growth patterns, and necrosis were observed in both cases. Case 2 displayed more marked cellular atypia than Case 1. Immunohistochemically, the tumor cells were diffusely positive for cytokeratin 5/6, p63/p40, SRY-related HMG-box 10 and Ki-67, but negative for other myoepithelial markers and p16. Finally, both cases were rediagnosed as BSCC-AdC. It is known that esophageal BSCC displays adenoid cystic-like features, and BSCC-AdC also sometimes occurs in the head and neck region. Clinicians should carefully differentiate BSCC-AdC from AdCC of the minor salivary glands and human papillomavirus-related carcinoma.

A case of small hepatocellular carcinoma with malignant ductular reaction.

Herein reported is the unique case of a small hepatocellular carcinoma (HCC) with several foci of a minor (10% in area) component of "malignant ductular reactions". The patient was 51-year-old man who was a drinker. HBV/HCV were negative. The tumor was small (12×10×11 mm), solid, expansile and reddish-brown, and contained fibrous septa. The background was cirrhotic without alcoholic features. Histologically, the tumor was well differentiated HCC, and, besides the HCC, it contained several small foci consisting of the following four biliary epithelial elements: clusters of small cells (CSC), ductules (D), ductular hepatocytes (DH), and bile ducts (BD). The proportion of area was as follows: HCC 90%, CSC 3%, D 3%, DH 2%, and BD 2%. These non-HCC elements were intimately admixed and formed several foci that were characteristically located in the fibrous septa (FS), except for CSC which were situated among HCC cells close to FS. There were gradual merges between HCC and CSC, CSC and D, D and DH, and D and BD, respectively. Cells of CSC and D resembled rat oval cells. Cells of these four elements had atypical features regarded as malignant. Immunohistochemically (IHC), HCC were positive for arginase, HepPar1, and less frequently CK7. CSC were positive for CK7. D were positive for arginase, HepPar1, CK7, CK19, EMA, and EpCAM. DH were positive for arginase, HepPar1, and CK7. BD were positive for CK7, CK19, EMA, EpCAM and mucin. Although such tumors as this have been termed stem cell-related cancers, our case lacked definite evidence for stem cell origin in histology as well as in the IHC that showed negativity for KIT, CD34, and OCT3/4. The above findings suggest that CSC, D, DH and BD are analogous to the ductular reaction seen in hepatic inflammation. Therefore, we termed the phenomenon "malignant ductular reaction". It is suggested in the present tumor that at first only HCC developed, and then HCC cells in the interface with FS transformed to CSC, like a fetal ductal plate. Then, the CSC gave rise to D, which in turn led to DH and BD in FS, all findings of which are most likely sequential considering embryonic biliary development. The idea that the present tumor was at first D carcinoma and then D developed on one hand into CSC and HCC, and on the other into DH and BD seems possible, but its probability appears low because the vast majority of the present tumor had the phenotype of HCC.

A case of small well-differentiated hepatocellular carcinoma with marked lymphocytic infiltrate.

We herein report a case of well-differentiated small hepatocellular carcinoma (HCC) with severe lymphocytic infiltrate (SLI) in a 55-year-old male patient with HCV-related cirrhosis. The patient had been followed-up because of HCV-related cirrhosis. He was found to have two small nodules in S8 by imaging techniques, and he underwent S8 segmentectomy. The resected liver showed two small nodules. Both were encapsulated, well-defined, solid, reddish and expansive nodules with fibrous septa. They measured 8 × 8 mm and 15 × 10 mm, respectively. Histologically, both tumours were pure HCC; the smaller showed SLI with lymphocytes/HCC cells ratio over 20, while the larger showed mild lymphocytic infiltration with lymphocytes/HCC cells ratio of 0.8. The smaller HCC was well-differentiated (trabecular thickness <3) HCC-SLI with Edmondson II = I cytologic atypia, while the larger was moderately-differentiated (trabeculae >3) HCC (Edmondson II>III>I). Extremely well-differentiated Edmondson I HCC or adenomatous hyperplasia areas were seen in the periphery of both HCCs. The patterns of SLI could be classified into the following three: sinusoids (S) type, portal tract (PT) type, lymph follicle (LF) type. In S-type, lymphocytes were infiltrated between the trabeculae. In PT-type, SLI was found to arise from extension from already inflamed PT within HCC or neighboring PT. The HCC cells frequently exhibited moth-eaten or piece meal necrosis in PT-type. In LF-type, lymphocytes were activated, and nuclear dusts were noted. It appeared that LF-type has arisen from preexisting S-type and/or PT-type. We speculated that the entry of SLI was from S in S-type, from incorporated inflamed PT in PT-type, and from both in LF-type. The approximate overall positive ratios of lymphoid cells among inflammatory cells were as follows: CD20 50%, CD3 70%, CD4 50%, CD8 30%, CD138 3%, CD163 40%, granzyme B 2%, smooth muscle actin (SMA) 30%, CD31 30%, CD21 2%, S100 3%, bcl-2 10%, CK19 1%, CD10 1%, CD30 0%, CD56 0% and Ki67 labeling index = 5%. EBV-ISH and HPV IHC were negative. Interestingly, Kupffer cells had myofibroblastic antigen in addition to macrophage antigens, and stellate cells expressed macrophage antigens aside from myofibroblastic antigens. These data suggest that, in the present case, pan-B-cells, pan-T-cells, helper T-cells, cytotoxic T-cells, plasma cells, macrophages, Kupffer cells, stellate cells, myofibroblasts, fibroblasts, endothelial cells, dendritic cells, Langerhans cells, and toxic molecules may play roles in tumour immunology.

Human ductal plate and its derivatives express antigens of cholangiocellular, hepatocellular, hepatic stellate/progenitor cell, stem cell, and neuroendocrine lineages, and proliferative antigens.

Molecular mechanisms of human ductal plate (DP) development and differentiation (DD) are unclear. The author immunohistochemically investigated expressions of cholangiocellular antigens (CEA, CA19-9, EMA, MUC1, MUC2, MUC5AC, MUC6, mucins, CK7, and CK19), hepatocellular antigens (HepPar1, AFP, CK8, and CK18), hepatic stellate/progenitor cell (HSC) antigens or stem cell (SC) antigens (C-erbB2, CD56, chromogranin, synaptophysin, bcl2, NSE, NCAM, KIT, and PDGFRA), and proliferating antigen (Ki67) in 32 human fetal livers (HFL). The DD of human intrahepatic bile duct (IBD) could be categorized into four stages: DP, remodeling DP, remodeled DP, and immature IBD. All the molecules examined were expressed in the DP and DP derivatives. These results suggest that human DP or DP derivatives have capacities to differentiate into cholangiocellular, hepatocellular, HSC, SC, and neuroendocrine lineages. The data also suggest that NCAM, KIT/SC factor-signaling, NSE, HGF/MET signaling, PDGFa/PDGFRA signaling, chromogranin, synaptophysin, and CD56 play important roles in DD of DP and biliary cells of HFL. DP, DP derivatives, and IBD in HFL have proliferative capacity.

Histopathological study using computer database of 10 000 consecutive gastric specimens: (2) malignant lesions.

Using a computer database, the author investigated the histopathology of 10 000 consecutive gastric specimens collected in the last 12 years 2002-2013 at his pathology laboratory in a relatively large hospital in Japan. Examination of histological sections was done when appropriate. The gastric specimens were made up of 8579 benign conditions and 1421 malignant lesions. The latter comprised gastric carcinoma in 1342 cases (94.4%), gastrointestinal stromal tumor (GIST) in 34 (2.4%), mucosal-associated lymphoid tissue (MALT) lymphoma in 25 (1.8%), non-Hodgkin's malignant lymphoma in 19 (1.3%), and metastatic carcinoma in 1 case (0.1%). Of the 1342 cases of gastric carcinoma, the histological type was as follows: tubular adenocarcinoma in 755 cases, papillary adenocarcinoma in 176, mucinous adenocarcinoma in 147, signet ring cell carcinoma in 145, poorly differentiated adenocarcinoma in 114, adenosquamous carcinoma in 4, and metastatic small cell carcinoma from the lung in 1. In surgically resected cases, the number of early gastric carcinomas was 258 and of advanced carcinoma, 521 cases. In GIST (n = 34), there were 2 cases of the epithelioid type and 32 of the spindle cell type. The size of GIST ranged from 1-15 cm, with a mean of 5.6 cm. KIT (CD117) was positive in 34/34 cases, CD34 in 31/34, desmin 2/34, and S100 4/34. A genetic analysis was performed in 6 cases of GIST, all of which showed point mutation of KIT and/or PDGFRA genes. In MALT lymphoma (n = 25), centrocyte-like cells and lymphoepithelial lesions were seen in every case. Helicobactor pylori infection was noted in 92%. In non-Hodgkin's lymphoma (n = 19), 17 cases were of diffuse large B-cell lymphoma, and 1 was peripheral T-cell lymphoma, while 1 was NK-cell lymphoma.

Multiple verrucous carcinomas of the oral cavity.

The author herein reports a case of multiple verrucous carcinomas (VCs) of the left lower gingiva. A 78-year-old man was admitted to our hospital because of gingival tumor. A biopsy revealed severe dysplasia. Surgical resection was performed. Grossly, there were three verrucous lesions (25, 20, 10 mm) in the left lower gingiva. Histologically, 2 tumors (4, 2 mm) were found in addition to the grossly visible 3 tumors. All the 5 tumors were VCs. The tumors showed verrucous and papillary proliferation of squamous epithelium with little cellular atypia. No invasive features were recognized. The dermis showed lymphocytic infiltration. The surrounding mucosa showed many broad foci of squamous cell carcinoma in situ and severe dysplasia (high grade intraepithelial neoplasm). Gradual merges between the VCs and squamous cell carcinoma in situ or severe dysplasia were frequently recognized. Immunohistochemically, the VC tumor cells and squamous lesions were negative for human papilloma virus antigens. P53 protein was expressed in all the VCs and squamous epithelial lesions: it was accentuated in the basal and suprabasal cells of VC. Ki-67 antigen was also expressed in the 5 VCs and in the squamous lesion, and Ki-67 labeling index ranged from 8 to 16 % in VC and from 37 to 62 % in the squamous lesions. These data support the multicentric nature of VC and that the severe dysplasia-carcinoma in situ sequence have been proposed in the etiology of VC.

Histopathological study using computer database of 10 000 consecutive gastric specimens: (1) benign conditions.

Using a computer database, the author investigated the histopathology of 10 000 consecutive gastric specimens, taken in the last 12 years (2002-2013) at the pathology laboratory of a Japanese hospital. Re-observation of the already examined histological sections was done when the histological diagnosis and findings on the computer data base were not very obvious. The gastric specimens were identified as 8579 benign conditions and 1421 malignant lesions. The 8579 benign conditions were comprised almost normal stomach in 74 cases (0.9%), chronic gastritis in 4374 (51.0%), benign gastric peptic ulcer in 2195 (25.6%), foveolar hyperplastic polyp in 1004 (11.7%), fundic gland polyp in 421 (4.9%), adenoma in 487 (5.6%), heterotopic pancreas in 9 (0.1%), pancreatic acinar metaplasia (PAM) in 8 (0.1%), and amyloidosis in 7 (0.1%). Chronic gastritis showed lymphocytic infiltration and frequently showed erosions and intestinal metaplasia. Gastric peptic ulcer showed exudate, necrosis, active inflammation, and regenerative atypia of the epithelium. Foveolar hyperplastic polyp revealed 23 malignant changes and frequently showed dysplastic glands and intestinal metaplasia. Fundic gland polyp demonstrated cystic dilations of fundic gland ducts. Gastric adenoma showed adenomatous proliferation in the superficial mucosa and cystic dilation of the epithelium under the adenoma. Heterotopic pancreas was located in the submucosa and consisted of acinar cells, ducts, and occasionally islets. PAM was a tiny lesion in the mucosa and consisted of only pancreatic acinar cells. Amyloidosis was primary amyloidosis with positive reaction with Congo-red stain.

Expression of cytokeratins in glioblastoma multiforme.

Little is known about the cytokeratin (CK) expressions in glioblastoma multiforme (GBM). The aim is to explore the CK expression in GM using immunohistochemistry (IHC). IHC study in 30 cases (median = 68 years, SE = 12.6) of GBM in brain. CK expression using AE1/3 antidody was seen in 29/30 (97 %) cases. There were no expressions of CK34BE12, CK5, CK6, CK7, CK8, CK14, CK 18, CK19, and CK20. Expression of p53 and glial fibrillary acidic protein (GFAP) were recognized in all 30 cases (100 %). All cases showed Ki-67 antigen labeling, index of which ranged from 6 to 43 % (m ± SD = 24 + 16). The IHC using CKAE1/3 in GBM very frequently shows positive reaction. The expression may cause difficulty in pathologic diagnosis in GBM, particularly in discrimination between GBM and metastatic carcinoma. The CK positivity in GM may be due to CK molecules other than CK34BE12, CK5, CK6, CK7, CK8, CK14, CK18, CK19 and CK20. GBM frequently expression p53 and high Ki-67 labeling.

Primary small cell carcinoma of prostate without immunoreactive neuroendocrine proteins but with expressions of KIT and platelet-derived growth factor-α.

Primary small cell carcinoma of the prostate is extremely rare. Herein reported is a case of primary small cell carcinoma of the prostate with immunohistochemical examination of KIT and platelet-derived growth factor-α. The present case is unique in that the small cell carcinoma did not express neuroendocrine antigens. A 68-year-old man was found to have high serum prostate-specific antigen, and biopsy showed malignant small tumor cells fulfilling the small cell carcinoma criteria of the World Health Organization. Immunohistochemically, tumor cells were positive for pan-cytokeratin, KIT, platelet-derived growth factor-α, p53, Ki-67 labeling = 65%, prostate-specific antigen and alpha-methylacyl-CoA racemase. Tumor cells were negative for vimentin, CD56, synaptophysin, chromogranin and neuron-specific enolase. Imaging modalities showed multiple metastases, and the patient was treated by chemotherapy. The present report is the fifth with immunohistochemistry of prostatic small cell carcinoma.

Ontogenic development of nerve fibers in human fetal livers: an immunohistochemical study using neural cell adhesion molecule (NCAM) and neuron-specific enolase (NSE).

The aim of the study was to investigate nerve fibers (NF) in human fetal livers. An immunohistochemical study was performed. NF were classified into portal tract innervation (PoI) and parenchymal innervation (PaI). The hilum area showed many Pol NF at 7 GW, and NF increased with gestational week (GW). Direct innervations to biliary epithelium were recognized. In large portal tracts, a few NCAM-positive mesenchymal cells were seen at 8 GW and many mesenchymal cells were noted around 12 GW. Apparent NF emerged around 15 GW, and NF increased with GW. Many NF plexuses were seen in 30-40 GW. In small portal tracts, no NF were seen in 7-10 GW. A few NCAM-positive mesenchymal cells emerged in 11 GW, and they increased thereafter. Apparent NF were seen around 20 GW and NF increased with GW. At term (40 GW), PoI NF were still immature. Ductal plate (DP) was positive for NCAM, NSE, chromogranin and synaptophysin, and direct innervations to DP were seen. The direct innervations to developing bile ducts and peribiliary glands were also seen. PaI NF were first seen at 21 GW and was consistent until 40 GW in which a few NF were seen in PaI. These observations suggest that PoI NF arise from committed portal mesenchyme. PaI NF are very immature at 40 GW. There are direct innervations to bile ducts, peribiliary glands, portal veins, hepatic arteries, and DP.