Coexistence of three nevus lipomatosus cutaneus superficialis with typical, cutaneous adenolipoma-like, and dermal spindle cell lipoma-like histopathological features in a patient.

We report an unique case of a patient who showed coexistence of three nevus lipomatosus cutaneus superficialis (NLCS) with typical, cutaneous adenolipoma (AL)-like, and dermal spindle cell lipoma (SCL)-like histopathological features. A 53-year-old woman presented with a 20-year history of skin-colored and slightly elevated nodules. These lesions were separately located on the lateral side (lesion 1) and medial side (lesion 2) of her left buttock and on her right thigh (lesion 3). Microscopically, all were ill-defined dermal lesions with some subcutaneous involvement and were mostly composed of mature adipocytes. The adipocytes formed small aggregates around blood vessels in the upper dermis. Lesions 1, 2, and 3 were diagnosed as NLCS, and additional features were recognized in lesions 2 and 3. Lesion 2 revealed eccrine glands and ducts amongst the lipomatous component, as seen in cutaneous AL. Lesion 3 had scattered CD34-positive spindle cells, which is representative of dermal SCL. These appearances were considered to be on the morphological spectrum of NLCS. In all three lesions, CD34-positive cells proliferated between the upper dermal blood vessels and their peripheral mature adipocytes. This pathological finding could be principal in NLCS and might be associated with its pathogenesis.

Cutaneous adenomyoepithelioma with histopathological heterogeneity: A case report.

Some skin adnexal tumors display both epithelial and myoepithelial cell populations and can be broadly categorized as biphasic tumors. These include apocrine hidrocystoma, mixed tumor, adenomyoepithelioma (AME), and adenoid cystic carcinoma (ACC). Myoepithelioma is the myoepithelial cell-predominant type in this category. Cutaneous AME is exceedingly rare and usually has a benign prognosis, but it is considered to have the potential for local recurrence and metastasis. We report the case of a 57-year-old man with a 1-year history of an ulcerated nodule on his scalp. Microscopically, it was a defined cutaneous nodule with a focal lobulated architecture, composed of epithelial cells forming ducts and myoepithelial cells distributed around the ducts. In addition to these findings of typical AME, the present case focally revealed atypical features, such as increased mitotic activity (7/10 high power fields), invasive growth, and necrosis. However, cytological atypia was not significant. We conclusively diagnosed cutaneous AME with atypical features, suggesting malignant potential. Moreover, areas showing appearances similar to apocrine hidrocystoma, mixed tumor, myoepithelioma, and ACC were focally observed. We present a unique case of cutaneous AME exhibiting histopathological heterogeneity. The recognition of morphological variation could be helpful in appropriately diagnosing and treating AME of the skin.

Podoplanin expression in cancer-associated fibroblasts predicts unfavourable prognosis in patients with pathological stage IA lung adenocarcinoma.

AIMS: Podoplanin expression in cancer-associated fibroblasts (CAFs) has been proposed as an unfavourable indicator in squamous cell carcinoma of the lung, but little is known about its clinical significance in early-stage lung adenocarcinoma. We evaluated the prognostic impact of podoplanin expression in patients with pathological stage (p-stage) IA lung adenocarcinoma as categorised by the 8th edition of the tumour-node-metastasis classification for lung cancer. METHODS AND RESULTS: Immunohistochemical analyses using anti-podoplanin antibody were performed on resected specimens from 158 patients with p-stage IA lung adenocarcinoma. When more than 10% of cancer cells or CAFs showed immunoreactivity with podoplanin, the specimens were classified as podoplanin-positive. Podoplanin-positive status in cancer cells (n = 8) was not correlated with clinicopathological factors or with patient prognosis. Podoplanin-positive status in CAFs (n = 41) was correlated significantly with poorer tumour differentiation (P < 0.001), the presence of lymphatic invasion (P < 0.001) and high-grade (solid and/or micropapillary) components constituting ≥1% of the entire tumour (P < 0.001). The log-rank test showed that podoplanin-positive status in CAFs was associated significantly with shorter disease-free survival (DFS) (P < 0.001) and disease-specific survival (P = 0.015). In Cox's multivariate analysis, podoplanin-positive status in CAFs had the most significant effect on shorter DFS [hazard ratio (HR) = 4.411, P = 0.004], followed by the presence of high-grade components (HR = 3.581, P = 0.013). CONCLUSIONS: Podoplanin expression in CAFs could be an independent predictor of increased risk of recurrence in patients with p-stage IA lung adenocarcinoma.

Cytoplasmic expression of maspin predicts unfavourable prognosis in patients with squamous cell carcinoma of the lung.

AIMS: Maspin is known to be a tumour suppressor protein, and its prognostic significance in patients with several types of cancer, including lung squamous cell carcinoma (SCC), has been reported. However, its prognostic impact on lung SCC has been controversial. We explored the prognostic value of maspin expression with particular reference to its subcellular localization in patients with lung SCC. METHODS AND RESULTS: Paraffin-embedded tissue samples from 101 curatively resected patients with lung SCC were analysed immunohistochemically using an antibody for maspin. Maspin positivity was defined as strong expression in only the cytoplasm and observed in 25 patients (24.6%). It correlated significantly with the presence of lymph node metastasis (P = 0.006) and higher pathological stage (P = 0.003). The patients were followed-up for 2-119 months (median: 50 months), and the maspin-positive group had shorter disease-free survival (DFS) and disease-specific survival (DSS) by log-rank test (P = 0.002, P = 0.016, respectively). Multivariate analysis revealed that the status of maspin was the only independent prognostic factor for DFS and DSS (P = 0.017, P = 0.047, respectively). CONCLUSIONS: Cytoplasmic expression of maspin could be an independent unfavourable prognostic indicator in patients with lung SCC.

Cytoplasmic maspin expression is a predictor of poor prognosis in patients with lung adenocarcinoma measuring <3 cm.

AIMS: Maspin is known to be a tumour suppressor protein, and few studies focused upon its prognostic significance in patients with small-size lung adenocarcinoma have been reported; however, its clinical significance remains controversial. We explored the prognostic value of maspin with particular reference to its subcellular localization in patients with resected lung adenocarcinoma measuring <3 cm. METHODS AND RESULTS: Immunohistochemical analyses were performed on resected 110 specimens of lung adenocarcinoma measuring <3 cm. Maspin positivity was defined as strong expression in only the cytoplasm and was observed in 27 patients (24.5%). It correlated significantly with the presence of lymph node metastasis (P = 0.009) and micropapillary component (P < 0.001). The patients were followed-up for 6-88 months (median: 71 months), and the maspin-positive group had shorter disease-free survival (DFS) and overall survival (OS) by log-rank test (P < 0.001, P < 0.001, respectively). Using Cox's multivariate analysis, the status of maspin was an independent prognostic factor for DFS and OS (P = 0.004, P = 0.022, respectively), as well as lymph node metastasis. CONCLUSIONS: Cytoplasmic maspin expression could be an independent poor prognostic indicator of patients with lung adenocarcinoma measuring <3 cm.

Extramammary Paget's disease: evaluation of the adnexal status of 53 cases.

Extramammary Paget's disease (EMPD) is a distinct form of malignant skin neoplasm. The clinicopathological significance of cutaneous adnexal involvement in EMPD has not been investigated in detail. Surgical specimens were obtained from 53 patients with primary EMPD. Tumor involvement of cutaneous adnexal structures was evaluated using histological parameters. The degree of involvement was scored on a scale of 0-2: 0, no involvement; 1, involvement of the upper portion of the adnexa; 2, involvement of the lower portion of the adnexa. A score of 2 was regarded as significant. The presence of comedo necrosis was also examined. Adnexal involvement was identified in 46 cases (86.8%). Comedo necrosis was observed in 6 cases (11.3%). The proportions of each parameter in in situ cases were as follows: significant adnexal involvement (score 2) in 15/26 (57.7%), and comedo necrosis in 3/26 (11.5%). The corresponding proportions in cases with invasion were 21/27 (77.8%) and 3/27 (11.1%), respectively. No significant differences in adnexal involvement and comedo necrosis were detected between in situ EMPD and invasive EMPD (p>0.05). The current study suggests that the degree of adnexal involvement and the presence of comedo necrosis are not associated with tumor progression in EMPD.

Poikilodermatous mycosis fungoides with a CD8+ CD56+ immunophenotype: a case report and literature review.

Mycosis fungoides (MF) represents the most common type of cutaneous lymphoma. MF shows varieties in both its clinical presentation and immunophenotype. We herein report one case of poikilodermatous MF with a CD8+ CD56+ immunophenotype and present a literature review. A 20-year-old Japanese woman presented with a 10-year history of multiple poikilodermatous and reddish or brownish patches with mild pruritus on the chest, abdomen, back, buttock and thighs. Histopathologically, small- to medium-sized atypical lymphocytes infiltrated into the epidermis, indicating epidermotropism, along the basal layer, and distributed in band-like appearance in the papillary dermis. Immunohistochemically, atypical lymphocytes expressed CD3, CD8, CD56, T-cell intracellular antigen (TIA)-1, granzyme B and beta F1 but lacked expression of CD4, CD20, CD30 and Epstein-Barr virus (EBV) latent membrane protein 1. An EBV-encoded small non-polyadenylated RNA-1 (EBER-1) signal was not detected. On the basis of these findings, the diagnosis of CD8+ CD56+ MF was established. Poikilodermatous MF with a CD8+ CD56+ immunophenotype, as presented herein, is extremely rare. Although further investigation is needed to fully clarify the nature of this aberrant phenotype of MF, we stress that it is important to recognize this rare immunophenotype of MF to distinguish it from aggressive cytotoxic cutaneous lymphomas.

Cancer-associated fibroblasts and CD163-positive macrophages in oral squamous cell carcinoma: their clinicopathological and prognostic significance.

BACKGROUND: Stromal cells are believed to affect cancer invasion and metastasis. The purpose of this study was to evaluate the distribution of cancer-associated fibroblasts (CAFs) and the incidence of tumor-associated macrophages (TAMs) in oral squamous cell carcinoma (OSCC), focusing on clinicopathological factors and patient prognosis, as well as cancer invasion. METHODS: The study included 108 patients with OSCC. Anti-α-smooth muscle actin, CD68, and CD163 antibodies were used to identify CAFs and TAMs. CAFs were divided into 4 grades on the basis of staining intensity: negative (0), scanty (1), focal (2), and abundant (3). The most intensive areas of macrophage concentration in each tumor invasive stroma were also evaluated. RESULTS: The cancer specimens were divided into Grade 0/1, Grade 2, and Grade 3 on the basis of CAF grade. In addition, they were divided into low- and high-grade groups on the basis of the number of CD68-positive and CD163-positive macrophages. The latter were significantly increased in the Grade 2 CAF group compared to the Grade 0/1 group (P = 0.009). Kaplan-Meier and multivariate survival analyses revealed that Grade 2 CAFs (P = 0.003) and high CD163-positive macrophage levels (P = 0.007) significantly correlated with a poor outcome in patients with OSCC, and that a high CD163-positive macrophage level was a significant and an independent prognostic factor (P = 0.045). CONCLUSIONS: Cancer-associated fibroblasts and CD163-positive macrophages may be potential prognostic predictors of OSCC.

Gastric adenocarcinoma with rhabdoid morphology.

Extrarenal rhabdoid tumors (ERRTs) are very rare neoplasms and have been reported in a range of organs, including sixteen cases in the stomach. We describe a woman aged 86 years who had an advanced gastric tumor with lymph node metastasis. The tumor mostly showed a diffuse arrangement with a small glandular region. The tumor cells were non-cohesive and had polygonal morphology with eccentric vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm, i.e. they showed rhabdoid features. Immunohistochemically, the rhabdoid tumor cells were strongly positive for cytokeratins and vimentin. However, a candidate tumor suppressor gene of rhabdoid tumors, the INI1 gene, showed no mutations or loss of expression in the tumor cells. Although ERRTs typically have an aggressive clinical course, the patient was still alive without any evidence of recurrence or metastasis at 26 months after surgery. The rhabdoid features of the present case seemed to be a variant of gastric adenocarcinoma.

Cutaneous epithelioid angiomatous nodule arising in capillary malformation.

Cutaneous epithelioid angiomatous nodule (CEAN) represents a rare, benign vascular lesion described by Brenn and Fletcher in 2004. To the best of our knowledge, the development of CEAN in a pre-existing vascular malformation has not been previously reported. A 52-year-old Japanese woman presented with multiple erythematous papules developed on violaceous macule of the right back that had been diagnosed as capillary malformation (CM) in childhood. Histopathological examination of one erythematous papule revealed a relatively well-circumscribed nodule composed mostly of epithelioid cells in the dermis. Abnormal dilated vessels were also identified around the lesion in the dermis, suggesting a CM. Immunohistochemically, the epithelioid cells were positive for CD31 and CD34. Staining for α-smooth muscle actin highlighted pericytes with epithelioid features. These findings were consistent with a diagnosis of CEAN arising in CM. The excised specimens of other erythematous papules revealed pyogenic granuloma (PyG) with focal epithelioid morphology accompanied by CM. We present the first reported case of CEAN arising in CM. Considering the histopathological findings, we speculate that CEAN of our case could be associated with PyG developed in pre-existing CM, and may thus be a variant of PyG with a mostly epithelioid appearance.

Geminin, Ki67, and minichromosome maintenance 2 in gastric hyperplastic polyps, adenomas, and intestinal-type carcinomas: pathobiological significance.

BACKGROUND: Geminin negatively regulates Cdt1 and induces the formation of prereplicative complexes by loading mini-chromosome maintenance proteins (Mcm) onto chromatin and limiting DNA replication to once per cell cycle. Recent studies have suggested that geminin expression is a marker of the S/G2/M phase of the cell cycle and is associated with a poor prognosis in various human malignancies. This study aimed to clarify the pathobiological role of geminin in intestinal-type gastric carcinoma, and its relationships with minichromosome maintenance 2 (Mcm2) and Ki67 expression. METHODS: We performed western blot analysis of seven human gastric cancer cell lines, and immunohistochemical analysis of 72 gastric mucosal lesions and 128 surgically removed advanced intestinal-type gastric carcinomas. Double-labeling immuno-fluorescence was performed to identify the coexpression of geminin and Ki67. RESULTS: Geminin was detected in all cell lines. Geminin labeling indices (LIs) in hyperplastic polyps, low-grade adenomas, high-grade adenomas, and intestinal-type adenocarcinomas were 3.9%, 10.5%, 18.6%, and 27.2%, respectively. The equivalent LIs for Ki67 and Mcm2 were 17.7%, 42.2%, 52.6%, and 59.7%; and 26.7%, 70.0%, 67.8%, and 77.8%, respectively. Double-labeling immunofluorescence revealed coexpression of geminin and Ki67 in both normal and tumor cells. The LI for geminin was significantly correlated with N stage, International Union Against Cancer (UICC) stage, Mcm2 LI, and Ki67 LI. Patients in stages I-IV and stage III with higher LIs for geminin (>25%) had significantly worse prognoses (P < 0.05 and P < 0.04, respectively). Univariate Cox regression analysis indicated that the overall survival of stage I-IV tumors was significantly correlated with high geminin LIs (relative risk [RR] = 1.94; P = 0.04). CONCLUSIONS: Geminin expression might reflect the biological nature of gastric intramucosal neoplasms and could be a possible prognostic marker in advanced intestinal-type gastric carcinomas.

Minichromosome maintenance-7 and geminin are reliable prognostic markers in patients with oral squamous cell carcinoma: immunohistochemical study.

BACKGROUND: Minichromosome maintenance (MCM) proteins act as the origin licensing machinery that regulates initiation of DNA replication. Geminin is a licensing repressor and prevents reinitiation of DNA replication by blocking reloading of MCM proteins at replication origins. Recent studies have proposed that MCM7 and geminin may be sensitive proliferative and prognostic markers of various malignant tumors. This study aimed to analyze the expression of MCM7 and geminin to clarify pathobiological significance in human oral squamous cell carcinomas (OSCCs). METHODS: We performed immunohistochemical analysis on 10 specimens of normal oral epithelia, 50 lesions with dysplasia and 113 OSCCs. Labeling indices (LIs) for MCM7, geminin and Ki-67 were evaluated, comparing with clinicopathological profiles. RESULTS: The mean LIs for MCM7 were 29.2% for normal epithelia, 32.2% for dysplasias, and 51.1% for OSCCs; the value was significantly higher in the last than in the former two (P < 0.01). The mean LIs for geminin were 6.8% for normal epithelia, 9.2% for dysplasias, and 21.3% for OSCCs; the value was significantly higher in the OSCCs (P < 0.01). The MCM7 LIs were correlated with the histological grade of OSCCs, in which the highest LIs were noted in the poorly differentiated type (P < 0.01). The survival rate was significantly lower in patients with a higher MCM7 LI (>49.5%) than in those with a lower LI (P < 0.05) at stage III-IV. However, the survival rate in the patients with a higher geminin LI (>19.5%) was significantly higher than in those with a lower LI (P < 0.05) at stage IV.

Acquired reactive perforating collagenosis with the histological features of IgG4-related sclerosing disease in a patient with Mikulicz's disease.

Acquired reactive perforating collagenosis has been reported in association with various conditions. To the authors' knowledge there has been no report of a patient with Mikulicz's disease showing acquired reactive perforating collagenosis. A 61-year-old Japanese man presented with non-pruritic multiple umbilicated papules with central keratotic and crusted plagues on the trunk, neck, and scalp. He had been diagnosed with Mikulicz's disease. Histologically, cutaneous biopsy showed a shallow cup-shaped lesion with a central crusted ulceration containing degenerated collagen in vertical strands, parakeratotic horny material, neutrophils, basophilic granular debris and elimination of collagen bundles from the dermis through to the epidermis. These clinical and histological findings suggested reactive perforating collagenosis. In addition, lymphocytes and plasma cells had infiltrated the dermis, with a tendency to be distributed around the sweat glands, accompanied by sclerotic fibrosis. On immunohistochemistry most plasma cells were positive for IgG and IgG4 (IgG4+/IgG+ plasma cells >50%). These histological findings of the skin were similar to findings previously reported for IgG4-related sclerosing diseases in other organs. Herein is described the first case of a patient with Mikulicz's disease showing acquired reactive perforating collagenosis accompanied by the histological features of IgG4-related sclerosing disease.

Benign Sebaceous Epithelioma with Carcinoid-like Trabecular Cell Arrangement.

A case of 75-year-old woman with sebaceous epithelioma was reported. The histological features were distinct in that it had a sinusoidal and carcinoid-like growth pattern, which has been reported in its malignant counterpart. Immunostaining for adipophilin was positive in the area with lipid-laden vacuolated cells, but the rest of tumor, which had cord-like nests, was negative. MIB index was 2%. CK5/6 and p40 were positive in the cord-like nesting areas. CK7, CK20, alpha SMA, and epithelial membrane antigen were negative in both the cord-like nesting areas and the adipose-like areas. The tumor was diagnosed as sebaceous epithelioma with a trabecular pattern. Dermatopathologists should be aware of this atypical histological pattern of benign sebaceous epithelioma.

Subcellular Localization of Maspin Correlates with Histone Deacetylase 1 Expression in Human Breast Cancer.

BACKGROUND/AIM: Maspin is known to be a tumor suppressor protein. Its nuclear localization and endogenous inhibition of histone deacetylase 1 (HDAC1) are considered crucial for its tumor suppressor activity. However, it remains unclear whether subcellular localization of maspin correlates with HDAC1 expression level in human breast cancer. PATIENTS AND METHODS: Immunohistochemical analyses were performed on 164 resected specimens of invasive breast carcinoma using antibodies for maspin and HDAC1. Subcellular localization of maspin protein and HDAC1 mRNA expression level in two human breast cancer cell lines (MCF7, MDA-MB-231) and mammary epithelial cell line (MCF10) were analyzed by immunofluorescence and quantitative polymerase chain reaction, respectively. RESULTS: The frequency of cytoplasmic-only, pancellular (combined nuclear and cytoplasm) and no staining of maspin were 31%, 14.0% and 55%, respectively. The cytoplasmic-only subgroup showed significantly higher histological grade (p=0.004), negative progesterone receptor status (p=0.003) and shorter disease-free survival compared to the pancellular subgroup (p=0.043). High HDAC1 expression was observed in 60% of cases and was significantly correlated with cytoplasmic-only staining compared to pancellular (p<0.001) or no staining (p=0.004). Immunofluorescence analysis revealed that maspin protein was localized mainly in the cytoplasm in MCF7 and MDA-MB-231 cells, while in both the nucleus and cytoplasm in MCF10A cells. HDAC1 mRNA levels were significantly up-regulated in MCF7 and MDA-MB-231 cells compared to MCF10A cells (p<0.001). CONCLUSION: High HDAC1 expression may contribute to the aggressiveness of human breast cancer with cytoplasmic-only expression of maspin.

Podoplanin Expression in Cancer-associated Fibroblasts Predicts Poor Prognosis in Patients with Squamous Cell Carcinoma of the Lung.

BACKGROUND/AIM: Podoplanin is a candidate cancer stem cell marker in squamous cell carcinoma (SCC). Several studies have reported the prognostic value of podoplanin expression in tumor cells in lung SCC but few have focused on its expression in cancer-associated fibroblasts (CAFs). The aim of this study was to analyze the prognostic significance of podoplanin expression, with special reference to the expression pattern in both tumor cells and CAFs. PATIENTS AND METHODS: Immunohistochemical analyses using anti-podoplanin antibody were performed on 126 resected specimens of lung SCC. When more than 10% of tumor cells or CAFs showed immunoreactivity with podoplanin levels as strong as those of the positive controls, the specimens were classified as a podoplanin-positive. RESULTS: Podoplanin-positive status in tumor cells (n=54) was correlated with a lower incidence of lymphatic invasion (p=0.031) but there were no significant differences in disease-free survival (DFS) and disease-specific survival (DSS) by the log-rank test. Podoplanin-positive status in CAFs (n=41) was correlated with more advanced stage (p=0.008), higher frequency of pleural invasion (p=0.002) and both shorter DFS (p=0.006) and DSS (p=0.006). In Cox's multivariate analysis, podoplanin-positive status in CAFs was an independent negative prognostic factor for DFS (p=0.027) and DSS (p=0.027). CONCLUSION: Podoplanin expression in CAFs might be an independent unfavorable prognostic indicator in patients with lung SCC, irrespective of the expression status of tumor cells.

[A case of myxoid liposarcoma in the right inguinal region: a case report].

We report a case of myxoid liposarcoma developed in the right inguinal region. A 45-year-old man visited our hospital with a chief complaint of painless right inguinal mass. He was diagnosed with right direct inguinal hernia for the first time and received a hernia repair. However, the size of the inguinal mass increased gradually after the operation. Then, the tumor was re-evaluated by imaging study such as ultrasonography, computed tomography and magnetic resonance imaging. A fatty mass 4.0 cm in diameter was demonstrated and the tumor was diagnosed as a liposarcoma preoperatively. In addition to the right high orchiectomy, surrounding fatty tissue was also removed at the time of the operation. Histological examination revealed a myxoid liposarcoma and the existence of several daughter regions outside the pseudo-capsule. Right spermatic cord and testis were intact. Postoperatively, he received 54 Gy dose of radiation therapy to right inguinal region for the prevention of the local recurrence of the disease.