White Adipocytes of the Uterine Cervix Tend to Appear in Women of Older Age, Postmenopause Status, and Higher Body Mass Index.

The human uterine cervix consists mainly of epithelium and stroma, including smooth muscle cells and fibrovascular tissues. Fat cells in the uterine cervix have been rarely reported, and the only previous research article has shown that intracervical adipocytes are unrelated to clinical factors. The aim of this study was to investigate the frequency of fat cells in the uterine cervix, as well as to evaluate the relationship between intracervical adipocytes and clinicopathologic factors. We retrospectively selected 405 cases in Japanese women who received cervical conization at our hospital between 2003 and 2017. Cervical conization was not performed during pregnancy or within 1 yr after childbirth. The prepared histologic specimens for pathologic diagnosis were available in all cases. Age, menopause status, body mass index, gravidity, and parity were selected clinical factors, which were obtained in 214 patients. The mean patient age was 42 yr (range, 22-80 yr). Intracervical white adipocytes were observed in 13% of patients (53/405), with no brown adipocytes detected. The existence of intracervical adipocytes was significantly correlated to older age (P<0.0001), postmenopause status (P<0.0001), and higher body mass index (P=0.0018). Intracervical adipocytes might undergo adipocytic metaplasia from cervical stromal cells in accordance with aging, postmenopause status, or weight gain. Our result also suggest that cervical malignancy involving fat cells does not necessarily imply parametrial invasion.

Clinical characteristics of adult T-cell leukemia/lymphoma infiltration in the gastrointestinal tract.

BACKGROUND: Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell malignancy caused by human T-cell leukemia virus type 1. The clinical course of ATLL is very heterogeneous, and many organs, including the gastrointestinal (GI) tract, can be involved. However, there are few detailed reports on ATLL infiltration in the GI tract. We investigated the clinical characteristics of ATLL infiltration in the GI tract. METHODS: This retrospective observational single-center study included 40 consecutive ATLL patients who underwent GI endoscopy. The patients' demographic and clinical characteristics and endoscopic findings were analyzed retrospectively. Patients with ATLL who were diagnosed by histological examination were divided into two groups based on GI tract infiltration. RESULTS: Multivariate analysis revealed that the absence of skin lesions was significantly associated with GI infiltration (P < 0.05). Furthermore, the infiltration group tended to have similar macroscopic lesions in the upper and lower GI tracts, such as diffuse type, tumor-forming type, and giant-fold type. CONCLUSIONS: GI endoscopy may be considered for ATLL patients without skin lesions.

Vocal cord inflammatory myofibroblastic tumor with mucoid deposits harboring TIMP3-ALK fusion: A potential diagnostic pitfall.

A 35-year-old Japanese man who had experienced hoarseness for 10 years presented with a vocal cord lesion. A gross examination revealed a left vocal cord polyp occupying two-thirds of the vocal space. The endoscopically resected lesion contained scattered atypical fibroblastic, stellate, or ganglion-like cells with mucoid stroma. Vacuolated cells were also seen. Lymphoplasmacytic infiltrate was largely undetectable. A vocal cord polyp was first suspected, but well-differentiated liposarcoma and inflammatory myofibroblastic tumor (IMT) were included in the differential diagnoses. The tumor cells were positive for anaplastic lymphoma kinase (ALK), calponin, and vimentin, and negative for other smooth muscle markers by immunohistochemistry. Structures resembling myofibroblasts were not observed by electron microscopy, which confirmed abundant rough endoplasmic reticulum in the tumor cells and accumulated lipid droplets in some tumor cells. ALK gene rearrangement was detected by fluorescence in situ hybridization, and TIMP3-ALK fusion was confirmed by 5' rapid amplification of cDNA ends. We diagnosed the lesion as an IMT, and an ALK-rearranged stellate cell tumor may be postulated. This is the first report of a fusion partner gene of ALK in a case of laryngeal IMT.

[A case of pancreatic cancer with clusters of invasive micropapillary carcinoma markedly reduced by chemotherapy].

A man in his 60s was hospitalized with multiple cerebral infarctions and referred for Trousseau's syndrome. Computerized tomography confirmed a 60-mm mass in the pancreatic head and swollen lymph nodes around the abdominal aorta. Fine needle aspiration cytology of the pancreatic lesion and laparoscopic para-aortic lymph node biopsy revealed adenocarcinoma, including clusters of invasive micropapillary carcinoma (IMPC). Chemotherapy (gemcitabine and nab-paclitaxel) markedly decreased the primary and metastatic lesions, and no recurrence was clinically detected 24 months later. To the best of our knowledge, reports of pancreatic IMPCs are rare. Our case was the seventeenth case of pancreatic cancer with IMPC. In this case, chemotherapy was markedly effective.

Penile warty mucoepidermoid carcinoma with features of stratified mucin-producing intra-epithelial lesion and invasive stratified mucin-producing carcinoma.

AIMS: Stratified mucin-producing intra-epithelial lesion (SMILE) and invasive stratified mucin-producing carcinoma (ISMC) are recently described cervical and penile lesions. We report an unusual case of mixed variant of penile squamous cell carcinomas with warty, usual and mucoepidermoid SMILE/ISMC features. METHODS AND RESULTS: A 62-year-old Japanese man had a glans penis lesion of one-and-a-half years' duration, suggesting malignancy. Partial penectomy and left inguinal lymphadenectomy were performed. Pathological evaluation revealed a mixed squamous cell carcinoma with warty, mucinous and usual features. The mucinous component resembled mucoepidermoid carcinoma (MEC) and SMILE/ISMC. Glandular differentiation was absent. All the diverse tumour components were negative for p16, which was confirmed by negative human papillomavirus (HPV) genotyping. The mucinous component was diffusely positive for cytokeratin 7 and largely negative for cytokeratin 5 and p63. Fluorescence in-situ hybridisation did not detect rearrangement in the MAML2 or EWSR1 genes. The tumour was pathological stage pT2, pN1 (AJCC prognostic stage group IIIA) and was disease-free 26 months after surgery. CONCLUSIONS: The lack of glands in the mucinous areas suggested that MEC should be separated from adenosquamous carcinoma (ASC). Penile SMILE/ISMC may occur without dependence upon HPV status. Further studies will be necessary to determine the pathogenesis and definition of penile SMILE/ISMC, the presence of true MEC arising from the glans penis and the clinicopathological differences of penile ASC, MEC and SMILE/ISMC. Herein, we refer to the SMILE-like penile lesion as 'mucinous penile intra-epithelial neoplasia'.

Acantholytic squamous cell carcinoma of the lung with marked lymphogenous metastases and high titers of myeloperoxidase-antineutrophil cytoplasmic antibodies: a case report.

BACKGROUND: Acantholytic squamous cell carcinoma (ASQCC), histologically characterized by intercellular bridge loosening, is recognized as a rare variant of squamous cell carcinoma (SQCC). ASQCC may demonstrate a worse prognosis than conventional SQCC. Pulmonary ASQCC is particularly rare; its biological behavior and prognostic data have not been reported. CASE PRESENTATION: We report the clinical and autopsy findings of a 71-year-old Japanese man with pulmonary ASQCC. Pulmonary lesions, suggestive of idiopathic interstitial pneumonia, were radiologically observed 3 and 6 years prior to the patient's most recent hospitalization; however, the patient did not undergo further medical examinations. Upon being discovered unconscious, the patient was admitted to our hospital. Dehydration and lower limb muscle weakness were noted, as were laboratory findings of coagulation abnormalities and renal dysfunction. Computed tomography helped confirm a 21-mm peripheral nodule in the upper left lobe of the lung, with associated swollen lymph nodes in the bilateral hilar, mediastinal, and para-aortic regions. Brain and spinal lesions, suggestive of neurological disturbances, were not found. Small cell lung carcinoma was suspected, upon admission, but high serum levels of squamous cell carcinoma antigen and cytokeratin-19 fragments were present. Therefore, advanced lung cancer, possibly SQCC, was diagnosed. The patient was treated with best supportive therapy, and died one month after admission. Hypercalcemia and high serum levels of parathyroid hormone-related protein (PTHrP) and myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) titers were observed. Progressive renal insufficiency was absent due to improved renal function subsequent to hydration. An autopsy helped confirm the left lung tumor as an ASQCC associated with pulmonary lymphangitic carcinomatosis and multiple metastases in the lungs and lymph nodes. Skin lesions suggesting malignant tumors were absent. The metastatic lesions consisted largely of acantholytic tumor cells, and the lungs showed usual interstitial pneumonia pattern; vasculitis was absent. CONCLUSIONS: This is the first reported case of pulmonary ASQCC resulting in an aggressive clinical course, with marked lymphogenous metastases and PTHrP-associated hypercalcemia. The high serum MPO-ANCA titers were clinicopathologically insignificant, but may have been related to the pulmonary interstitial lesion. Pulmonary ASQCC represents a highly malignant subset of lung cancer.

Anaplastic variant of diffuse large B-cell lymphoma with hallmark cell appearance: Two cases highlighting a broad diversity in the diagnostics.

The anaplastic variant of diffuse large B-cell lymphoma (A-DLBCL) is morphologically defined but remains an enigmatic disease in its clinicopathologic distinctiveness. Here, we report two cases involving Japanese women aged 59 years, both with A-DLBCL with the hallmark cell appearance and both indistinguishable from common and giant cell-rich patterns, respectively, of anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma. Case 1 was immunohistochemically positive for CD20, CD79a and OCT-2 but not for the other pan-B-cell markers, CD30 and ALK. Case 2 showed CD20 and CD30 positivity for 50% and 20% of tumor cells in addition to strong expression of p53 and MYC. Both were positive for fascin without Epstein-Barr virus association. Our cases provide additional support for the earlier reports that A-DLBCL exhibits clinicopathologic features distinct from ordinal diffuse large B-cell lymphoma (DLBCL), and documented its broader morphologic diversity than previously recognized. They also shed light on the unique feature of absent expression of pan-B-cell markers except for CD20 and CD79a, suggesting that A-DLBCL may biologically mimic a gray zone or intermediate lymphoma between DLBCL and classic Hodgkin lymphoma.

Characteristic findings of high-grade cervical intraepithelial neoplasia or more on magnifying endoscopy with narrow band imaging.

BACKGROUND: Colposcopy, which is a standard modality for diagnosing cervical intraepithelial neoplasia (CIN), can have limited accuracy owing to poor visibility. Flexible magnifying endoscopy with narrow band imaging (ME-NBI) has excellent diagnostic accuracy for early gastrointestinal neoplasms and is expected to be highly useful for CIN diagnosis. This study aimed to determine the characteristic findings and evaluate the diagnostic ability of ME-NBI for lesions ≥ CIN 3. METHODS: A well-designed prospective diagnostic case series conducted at multiple tertiary-care centers. A total of 24 patients who underwent cervical conization with a preoperative diagnosis of high-grade squamous cell intraepithelial lesions (HSILs) or lesions ≥ CIN 3 were enrolled. Prior to conization, still images and video of ME-NBI were captured to investigate the cervical lesions. The images were reviewed based on histological examination of the resected specimens. RESULTS: The NBI-ME images revealed the following abnormal findings: (1) light white epithelium (l-WE), (2) heavy white epithelium (h-WE), and (3) atypical intra-epithelial papillary capillary loop (IPCL). Pathological examination of the resected specimens confirmed cervical lesions ≥ CIN 3 in 21 patients. The ME-NBI findings were classified into four groups: l-WE, l-WE with atypical IPCL, h-WE, and h-WE with atypical IPCL, at rates of 0, 23.8, 9.5, and 66.7%, respectively. Additionally, all 3 patients with micro-invasive carcinoma showed a strong irregularity of IPCLs. CONCLUSION: The lesions ≥ CIN 3 demonstrated characteristic ME-NBI findings of h-WE alone, or l-/h-WE with atypical micro-vessels. This study indicates that ME-NBI may have novel value for CIN diagnosis.

Clinicopathologic study of 10 cases of gastric adenocarcinoma with hepatoid or enteroblastic differentiation.

Gastric adenocarcinoma with hepatoid or enteroblastic differentiation (GAHED), known also as AFP-producing carcinoma, is a rare neoplasm. Ten cases with GAHED and 209 cases without GAHED were selected. Clinicopathological features of GAHED were investigated. The disease-free survival (DFS) of the GAHED group was compared with that of the non-GAHED group. Grossly, the tumours consisted of two early types and eight advanced types. Histologically, all tumours were composed of various proportions of tubular, cribriform, papillary, solid, and/or trabecular growth patterns of clear to slightly eosinophilic tumour cells. Hyaline globules were observed in all tumours. AFP and Hep-Par1 were immunoreactive in all tumours. In fluorescence in situ hybridisation of HER2 gene/chromosome 17, the amplification of HER2 gene was observed in two cases that showed positive reaction for HER2 protein. Clinical follow-up was available in nine cases. Regarding the clinical outcome, 3 and 6 patients were alive without disease and alive with disease, respectively. In a statistical analysis, the DFS of the GAHED group was significantly worse than that of the non-GAHED group. GAHED is morphologically characterised by various growth patterns of clear to slightly eosinophilic tumour cells and intracytoplasmic possession of hyaline globules. This tumour may have the potential to behave in an aggressive clinical fashion.

Various patterns of acute alveolar haemorrhage in patients with microscopic polyangiitis: a clinicopathological study of four cases.

It is well known that acute alveolar haemorrhage (AAH) is attributed to capillaritis in most cases with microscopic polyangiitis (MPA). In this article, we explore the cause of alveolar haemorrhage in MPA patients. In the present study, we extracted four autopsy cases of MPA with AAH. Patient's sex and age, cause of alveolar haemorrhage, therapy, follow-up duration, and cause of death were investigated. As a result, alveolar haemorrhage was caused by diffuse alveolar damage (DAD) due to candidiasis or influenza virus infection, haemorrhagic infarct due to aspergillosis, capillaritis due to MPA, vasculitis due to cytomegalovirus (CMV), and herpes simplex virus (HSV) infection. All patients received corticosteroid therapy, and one patient additionally underwent administration of cyclophosphamide. The duration of follow-up ranged from one to 26 months with a mean of eight months. All patients died of respiratory failure. In summary, clinicians and pathologists should recognise some causes of alveolar haemorrhage in MPA patients, which include DAD, haemorrhagic infarct, virus-associated vasculitis, or MPA-associated capillaritis.

A review of ALK-rearranged renal cell carcinomas with a focus on clinical and pathobiological aspects.

ALK-rearranged renal cell carcinoma (ALK-RCC) has been recently proposed and incorporated into the recent World Health Organisation Classification of renal tumours as a provisional entity. In this article, we review ALK-RCC with a focus on clinical and pathobiological aspects. Seventeen cases have been described to date. ALK-RCC accounts for less than 1% of all renal tumours. The age of patients ranges from 6 to 61 years with a mean age of 29.6 years. Grossly, the tumour forms were ill-demarcated or well demarcated solid mass in the renal medulla. Histologically, RCC with VCL-ALK translocation resembles renal medullary carcinoma and mucinous cribriform pattern, signet-ring cell pattern and solid rhabdoid pattern are often observed in RCC with non-VCL-ALK fusion. Immunohistochemically, ALK protein diffusely expresses and TFE3 is often expressed. ALK gene can fuse to VCL, TPM3, EML4, HOOK1 or STRN gene. A break-apart fluorescence in situ hybridisation study is clinically available for the practice of definite diagnosis. ALK inhibitor therapy will provide great benefit for patients with advanced stage of ALK-RCC in the near future.

Colon cancer with micropapillary carcinoma component: a clinopathologic study of 9 cases.

Recently, colon cancer with micropapillary pattern (MPP) has been identified. MPP is defined as tight tufts surrounded by cleft-like space and lacking true fibrovascular cores and showing reverse polarity. In this article, we studied nine cases of colon cancer with MPP. MPP usually accounted for a minor component in total tumour volume, which ranged from 3 to 40% with a mean percentage of 19.2%. Associated histological subtype showed moderately differentiated tubular adenocarcinoma in all cases. The reverse polarity of villin (9/9, diffuse) in MPP component was superior to that of CA125 (5/9, focal) or CD10 (5/9, diffuse 2/9, focal 3/9). In clinicopathological indicators such as sex, tumour location, tumour depth, lymphovascular invasion, lymph node metastasis, or pathological stage and clinical behaviour, there was statistically no difference between the MPP group and the non-MPP group of the colon. In conclusion, colon cancer with MPP is characterised by frequent association with moderately differentiated tubular adenocarcinoma as a minor component. Villin immunohistochemistry is useful in the detection of reverse polarity of MPP of colon cancer.

Acquired cystic disease-associated renal cell carcinoma: a clinicopathological study of seven cases.

The disease entity of acquired cystic disease (ACD)-associated renal cell carcinoma (RCC) has been recently incorporated into the international renal tumor classification. However, there are a few descriptions on clinicopathologic features. We performed a clinicopathologic study of seven cases with ACD-RCC. All tumors were incidentally found. Histologically, the tumor consisted of microcystic or cribriform pattern of neoplastic cells with deeply eosinophilic to oncocytic cytoplasm in the stroma of oxalate crystal deposition. Three cases contained the area of sarcomatoid transformation, of which one case also demonstrated rhabdoid phenotype foci. Six among seven patients had a hemodialysis history of more than 10 years and two patients showing the dedifferentiation had a hemodialysis history of more than 20 years. The follow-up duration ranged from 18 to 107 months with a mean of 59.1 months. Regarding the outcome, four patients were alive without disease. One patient was alive with metastasis 10 months after the operation. No patient died of disease. Finally, ACD-RCC generally pursues a favorable clinical course, but tumors with a hemodialysis history of more than 20 years may cause the dedifferentiation such as sarcomatoid change or rhabdoid features and this phenomenon may lead to worse clinical outcome.

Clinicopathological study of 5 cases of renal cell carcinoma with t(6;11)(p21;q12).

Renal cell carcinoma (RCC) with t(6;11)(p21;q12) has been incorporated into the recent WHO classification. We performed a clinicopathological study of 5 cases with such a tumor. The patients consisted of 4 males and 1 female. The age of patients ranged from 17 to 57 years with a mean age of 38.6 years. Tumor sizes ranged from 2.8 to 11 cm with a mean value of 6.5 cm. Despite immunotherapy and molecular-targeted therapy, one patient died of the disease 28 months after the surgery. Grossly, the cut surface of this tumor showed grayish white color in at least the focal area of all tumors. Furthermore, hemorrhage, daughter nodules and cystic changes were observed in two, three, and two tumors, respectively. Morphologically, all the tumors consisted of two components of large cells and small cells, and the latter surrounded basement membrane-like materials, forming rosette-like structures. Immunohistochemically, nuclei of tumor cells in all cases were positive for TFEB. Fluorescence in situ hybridization study confirmed the TFEB gene break in two tumors. Finally, urologists and pathologists should bear in mind that this tumor may occur in young adults to adults and might behave in an aggressive fashion. Break-apart FISH is useful for the definite diagnosis.

A novel case presenting with an unusual ureteral diverticular lesion similar to adenomyomatous hyperplasia of the gallbladder.

We present the first case of an unusual ureteral diverticular lesion demonstrating similarities to adenomyomatous hyperplasia of the gallbladder. A 68-year-old asymptomatic Japanese man with high prostate-specific antigen levels was clinically evaluated. Left hydronephrosis and benign prostatic hyperplasia were detected. A bilateral retrograde pyelogram revealed that the upper and middle portions of the left ureter exhibited an irregular narrow lumen and some pooling of contrast material, which was compatible with ureteral pseudodiverticulosis. Although no malignant cells were seen on cytology, computed tomography detected a fusiform shaped lesion with a circumferential thick wall including multiple diverticulae. Left nephroureterectomy was performed because malignancy could not be ruled out. Pathology demonstrated that the ureteral lesion showed a localized thick wall consisting of multilocules and/or multicysts and a hyperplastic muscularis propria. The cysts were mostly seen in the muscularis propria or a deeper site. The inner layers of the cysts were lined with normal urothelium, and some cysts opened onto the mucosal surface, indicating that they were derived from invaginated mucosal epithelium. We believe that this lesion may be a novel form of diverticular disorder demonstrating similarities to adenomyomatous hyperplasia of the gallbladder.

High preoperative levels of serum glypican-3 containing N-terminal subunit are associated with poor prognosis in patients with hepatocellular carcinoma after partial hepatectomy.

Glypican-3 (GPC3) is a glycosylphosphatidylinositol-anchored cell surface glycoprotein overexpressed in hepatocellular carcinoma (HCC) cells and may serve as a potential molecular target for therapeutic intervention. This study evaluated the prognostic significance of serum GPC3 in HCC patients receiving curative surgery. A novel sandwich enzyme-linked immunosorbent assay for the quantitative and sensitive determination of serum GPC3 N-terminal subunit antigen (sGPC3N) was developed and used to measure sGPC3N levels in 25 healthy volunteers and 115 HCC patients who underwent curative partial hepatectomy. The relationships between sGPC3N and clinicopathologic features were analyzed and the prognostic impact on overall survival (OS) or disease-free survival (DFS) was also investigated. Mean and median levels of sGPC3N in healthy controls were 110.12 and 115.95 pg mL(-1) , respectively, with 185.52 pg mL(-1) (mean + 2 SD) being set as the upper limit of the normal range. In HCC patients, sGPC3N levels were significantly increased (mean/median, 405.16/236.19 pg mL(-1) ) compared to healthy controls (p < 0.0001), and 60% of HCC cases (69/115) showed sGPC3N levels that were higher than the upper normal limit. High sGPC3N levels were significantly associated with serum AFP level, high Child-Pugh score and positive HCV. Kaplan-Meier analysis indicated that elevated pre-operative sGPC3N was associated with shorter OS and DFS after hepatectomy (p ≤ 0.01). Multivariate analysis revealed elevated sGPC3N as an independent poor prognostic marker for OS (p < 0.05) and DFS (p < 0.01). The pre-operative sGPC3N level serves as an independent prognostic biomarker in HCC patients.

Primary pulmonary angiosarcoma: A case report.

Primary sarcoma is uncommon in the lung, and primary angiosarcoma is exceedingly rare. We report a case of primary pulmonary angiosarcoma of the left lung with emphasis on its growth pattern in the lung. A 48-year-old Japanese man was admitted to our hospital because of dyspnea on exertion. He was subsequently found to have left pleural effusion. Computed tomography shows a nodular lesion measuring 7 × 4 cm in his left lung. Obstruction of the left inferior lobar bronchus was observed, and endobronchial biopsy suggested angiosarcoma. Left pneumonectomy was performed. On macroscopic examination of the cut surface, multiple nodular lesions were observed particularly in portions around branches of pulmonary artery along bronchioles. Histological examination revealed vascular channel-like structure with vague lumen formations by atypical polygonal or spindle-shaped neoplastic cells. Immunohistochemically, the neoplastic cells are positive for FLI-1, ERG, CD31 and von Willebrand factor/factor VIII-related antigen, but not CD34. Angiosarcoma is a particularly rare form of primary pulmonary tumors, and this case report describes its unique macroscopic growth pattern in the lung.

Unusual cystic hamartomatous lung lesion with clinical manifestation of subpleural bullae in a woman of reproductive age: A case report.

Pulmonary hamartoma is a common benign lung disorder, and most cases show solid nodules. Here, we documented the clinicopathological features of a growing, bulla-like, multilocular hamartomatous lung lesion in a woman of reproductive age. To the best of our knowledge, this disorder has not been reported in the literature to date. An asymptomatic 29-year-old Japanese woman with no significant past medical history was referred to our institution for surgical treatment of a bullous lesion in the right upper lobe because the pulmonary lesion had enlarged to multilocular cysts, including a giant bulla, within 1 year, leading to compression of the right lung. The bullous lesion, which was projected from the apex of the lung via a narrow stalk, showed nonemphysematous, multiloculated tissue. The wall mimicked a bronchiolar structure with ciliated, nonatypical epithelium and layers of nonatypical spindle cells that were positive for smooth muscle markers and sex steroid hormone receptors. No cartilage was included in the lesion. We believe that this may be a novel form of hamartoma. This disorder may be included in a differential diagnosis of subpleural bullous diseases in women of reproductive age.

Aberrant expression of monocarboxylate transporter 4 in tumour cells predicts an unfavourable outcome in patients with hepatocellular carcinoma.

BACKGROUND & AIMS: The tumour cell microenvironment, which includes local oxygen saturation, pericellular pH and stromal cells, can modulate tumour progression. This study determined the prognostic impact of infiltrating tumour-associated macrophages and the expression of monocarboxylate transporter 4 (MCT4) and glypican 3 (GPC3) in hepatocellular carcinoma (HCC) clinical specimens. METHODS: A total of 225 cases of resected HCC were subjected to immunohistochemical analyses of CD68, CD204, MCT4 and GPC3. Immunoreactivities and other common clinicopathological parameters were subjected to univariate prognostic analyses for overall survival (OS, n = 225) and disease-free survival (DFS, n = 222). All variables with prognostic impact were further analysed in multivariate analysis. RESULTS: Increased intratumoural infiltration of CD204-positive or MCT4-positive macrophages suggested shorter OS (P = 0.015 or P = 0.001 respectively), but DFS was not altered. The GPC3 score (with an emphasis on circumferential immunoreactivity) was correlated with shorter OS and DFS. Aberrant expression of MCT4 in HCC cells was observed in a subset of HCC cases (21%, 47/225). In those cases, significantly poorer OS (P < 0.0001) and DFS (P = 0.0003) were observed, and there was a positive correlation with the intratumoural infiltration of CD204- or MCT4-positive macrophages and the GPC3 score. Multivariate analysis showed that aberrant MCT4 expression in HCC cells was an independent prognostic factor for shorter OS (P = 0.018) and DFS (P = 0.006) after resection of HCC. CONCLUSION: Aberrant expression of MCT4 in carcinoma cells serves as a novel, independent prognostic factor for HCC, indicating a poorer patient outcome.