Unclassified epithelioid vascular tumor with hemangioendotheliomatous features and lymphatic differentiation

Reported herein is an unusual vascular tumor that arose in the little finger of a 10-year-old boy. The tumor consisted of a vaguely demarcated nodular mass, which was located in the subcutaneous layer and measured 1 cm in diameter. Microscopic characteristic findings of this tumor were epithelioid nests, admixed with focal components with retiform features, intraluminal papillary tufts, and spindle cells. These features resemble those of subtypes of hemangioendotheliomas. On immunohistochemistry CD31, CD34 and D2-40 were diffusely expressed in the tumor cells, representing prominent lymphatic differentiation. These findings are not characteristic of any established types of vascular tumors. The differential diagnosis for the current peculiar tumor are discussed.     

Palmar atypical lipomatous tumour with spindle cell features (well-differentiated spindle cell liposarcoma): a rare neoplasm arising in an unusual anatomical location

Lipomatous tumours, both benign and malignant, arising on the hands are uncommon. We present a rare atypical lipomatous tumour with spindle cell features (synonym: well-differentiated spindle cell liposarcoma) arising on the left palm of a 54-year-old male patient. The neoplasm presented as a long-standing, exophytic neoplasm measuring 9×9 cm. The well-circumscribed neoplasm was completely excised, and margins were tumour free. Histologically, the neoplasm showed features closely resembling spindle cell lipoma, being composed of mature adipocytic cells associated with bland, neuroid spindle cells staining positively for CD34. However, focally, atypia of adipocytic and stromal cells as well as scattered lipoblasts were noted, and immunohistochemical stainings showed focal overexpression of MDM 2 and CDK4. Aypical lipomatous tumour with spindle cell features may arise very rarely in palmar location and has to be distinguished from a number of benign and malignant mesenchymal neoplasms.     

Malignant granular cell tumor with unusual histological features

Malignant granular cell tumor, although uncommon, should be differentiated from a number of granular cell-containing tumors. Reported herein is a distinctive variant of malignant granular cell tumor, clinically presenting as a rapidly enlarging scrotal mass, in which some areas morphologically displayed features indistinguishable from Kaposi sarcoma. Cells in areas simulating Kaposi sarcoma were immunohistochemically the same as typical granular cells in other portions of the tumor. The recognition of this pattern is important because it may predominate and overshadow the original nature of tumor.     

Hepatoid differentiation in renal cell carcinoma: a rare histologic pattern with clinical significance

Hepatoid adenocarcinoma is a rare extrahepatic aggressive tumor defined by morphologic and immunohistochemical evidences of hepatoid differentiation. In this study, clinicopathologic features of 3 cases of hepatoid renal cell carcinoma (RCC) were analyzed. Case I was a 53-year-old man with stage III, with 1,460 ng/ml of serum alpha-fetoprotein (AFP) and a 12 cm-sized stage III RCC, which was a combined clear cell and papillary RCC type 2 with sarcomatoid dedifferentiation. Case II was a 62-year-old woman with stage IV, 6.5-cm clear cell RCC and 40,800 ng/mL of serum AFP. Case III was a 51-year-old woman with stage I, 1.6-cm Xp11 translocation RCC and 313.3 ng/mL of serum AFP. Cases I and II died of the disease at 26 and 21 months after radical nephrectomy, respectively. Case III was alive without the disease for 20 months at the last follow-up. Microscopically, three cases show hepatoid carcinoma areas with eosinophilic to clear cells, arranged in trabeculae, separated by thin sinusoidal vessels, in addition to diagnostic features of corresponding RCC subtypes. The tumor cells in these hepatoid carcinoma areas as well as at least focally in RCC areas were immunopositive for AFP in all three cases, but were immunonegative for other hepatic markers (Hep Par1, polyclonal CEA, and glypican 3). This report suggests that the hepatoid features with AFP production are aberrant differentiation that can be developed in various RCC subtypes. Recognizing hepatoid RCC will help explain abnormal elevation of serum AFP levelS, which can be used as a serum surveillance marker.     

Glioblastoma with Oligodendroglioma Component (GBM‐O): Molecular Genetic and Clinical Characteristics

Glioblastoma (GBM) is an aggressive primary brain tumor with an average survival of approximately 1 year. A recently recognized subtype, glioblastoma with oligodendroglioma component (GBM‐O), was designated by the World Health Organization (WHO) in 2007. We investigated GBM‐Os for their clinical and molecular characteristics as compared to other forms of GBM. Tissue samples were used to determine EGFR, PTEN, and 1p and 19q status by fluorescence in situ hybridization (FISH); p53 and mutant IDH1 protein expression by immunohistochemistry (IHC); and MGMT promoter status by methylation‐specific polymerase chain reaction (PCR). GBM‐Os accounted for 11.9% of all GBMs. GBM‐Os arose in younger patients compared to other forms of GBMs (50.7 years vs. 58.7 years, respectively), were more frequently secondary neoplasms, had a higher frequency of IDH1 mutations and had a lower frequency of PTEN deletions. Survival was longer in patients with GBM‐Os compared to those with other GBMs, with median survivals of 16.2 and 8.1 months, respectively. Most of the survival advantage for GBM‐O appeared to be associated with a younger age at presentation. Among patients with GBM‐O, younger age at presentation and 1p deletion were most significant in conferring prolonged survival. Thus, GBM‐O represents a subset of GBMs with distinctive morphologic, clinical and molecular characteristics.     

筛状结构为主的涎腺基底细胞腺瘤临床病理特征及免疫表型

目的探讨以筛状结构为主的涎腺基底细胞腺瘤(basal cell adenoma,BCA)的临床病理学及免疫表型特征。方法回顾性分析4例以筛状结构为主的涎腺BCA临床病史和病理学特征,采用免疫组化法检测CK、CK14、CK8/18、CK19、EMA、CD10、CD117、BCL-2、CDX-2、SMA、S-100、p63、p53、EGFR、Ki-67的表达。结果 4例以筛状结构为主的BCA均生长缓慢,分界清楚,无周围组织浸润,有被膜内浸润但未突破被膜,镜下见瘤组织中筛状结构占50%以上。免疫表型:肿瘤细胞中CK、EMA、CD10、CD117、BCL-2、CDX-2、p53、EGFR均呈(+),CK14、CK8/18、SMA、S-100均呈(),CK19和p63呈();Ki-67增殖指数<1%。结论以筛状结构为主的BCA较罕见,与腺样囊性癌(adenoid cystic carcinoma,ACC)不易区分,结合临床病理及免疫表型特征等可进行鉴别。     

具有血管周上皮样细胞分化的肿瘤15例临床病理分析

目的探讨具有血管周上皮样细胞分化的肿瘤(perivascular epithelioid cell tumor,PEComa)临床病理特征及免疫表型。方法对15例PEComa行EnVision两步法免疫组化及特殊染色,并分析其临床表现、病理学特征和免疫组化特点。结果 15例PEComa中13例为女性,且术后无复发。肿瘤可发生在身体任何部位,以肝脏和肾脏最多见,有包膜,多为实性,可有出血。特征性组织学改变是肿瘤细胞围绕血管生长。PAS染色显示该肿瘤细胞中有糖原物质沉积,弹力纤维染色显示该肿瘤中的血管壁缺乏弹力层。免疫组化显示所有PEComa病例均明显表达HMB-45、Melan-A、SMA,Ki-67阳性率低。结论 PEComa是一组具有恶性潜能的肿瘤,多发于女性,来源于血管周上皮样细胞。大部分肿瘤呈良性过程,生物学分级极低,预后良好;极少部分病例可发生转移,预后不佳。免疫组化检测对其组织来源、生物学行为具有提示意义,并可辅助诊断。     

Melanotic oncocytic metaplasia of the nasopharynx: a case report with a focus on immunohistochemical analyses and literature review

Melanotic oncocytic metaplasia (MOM) of the nasopharynx is an extremely rare lesion, with only 21 cases reported in English literature to date. MOM typically occurs near the Eustachian tube opening in Asian men in their 60 s to 70 s. Here, we present a case of MOM in a 57-year-old Japanese man who is a heavy smoker. The patient did not have complaints; MOM was diagnosed incidentally as 4 flat elevated lesions with brown to black discoloration, ranging from 2 to 3 mm in maximal diameter, were found in the right torus tubarius. On suspecting melanoma, the largest lesion was biopsied. Microscopic examination identified both oncocytic metaplasia and melanin pigmentation of the epithelium in the same gland. Upon immunohistochemical examination, melanocytes displayed reactivity for 3 out of 4 melanocytic markers; immunopositivity for S-100 protein, Melan-A, and MITF and immunonegativity for HMB-45 was observed. Normal melanocytes in the nearby surface respiratory epithelium displayed the same pattern of immunoreactivity. Immunopositivity for S-100 protein and immunonegativity for HMB-45 have been previously reported in MOM. Reduction of stimulation of melanocytes in a longstanding lesion like MOM may explain the immunonegativity for HMB-45. S-100 protein, in conjunction with more specific marker for melanocytes, Melan-A or MITF, could prove the definite presence of melanocytes in this case of MOM. As it has been shown by previous reports that MOM pursues a benign course, it will be sufficient to follow up the patients regularly for the remaining 3 lesions.     

Malignant uterine perivascular epithelioid cell tumor: histopathologic and immunohistochemical characterization of a rare tumor in a post-menopausal woman

Background: Perivascular epithelioid cell tumors (PEComas) are rare, mesenchymal neoplasms composed of epithelioid cells exhibiting myogenic and melanocytic differentiation. The uterus is an infrequent site of involvement. The most common histopathologic mimics include leiomyosarcoma, endometrial stromal sarcoma, undifferentiated uterine sarcoma, and malignant melanoma. Rendering an accurate histopathologic diagnosis is essential, owing to the prognostic and therapeutic implications. Case: A 65-years-old post-menopausal woman presented with post-menopausal bleeding, abdominal pain, and heaviness for the last four months. Ultrasound abdomen revealed a large uterine mass replacing the endometrial cavity. She underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. Result: Microscopically, a circumscribed tumor with tumor cells arranged in sheets and interlacing fascicles, with interspersed fine capillary network, was seen. The individual tumor cells were epithelioid to spindle with moderate pleomorphism, round nuclei, vesicular chromatin, prominent macronucleoli, and moderate cytoplasm. Mitosis was 2-3/50 HPFs. On immunohistochemistry, tumor cells were positive for HMB-45, Melan-A, and smooth muscle actin and were negative for h-caldesmon, TFE3, S-100, CD10, and pan-cytokeratin. Based on the histopathologic and immunohistochemical features, a final diagnosis of malignant uterine PEComa was rendered. Conclusions: This index report describes the characteristic histopathologic and immunohistochemical features of malignant uterine PEComa and highlights the salient features that distinguish it from other commonly encountered histopathologic mimics.     

Carcinoma of the oesophagus with spindle cell features

There is considerable confusion surrounding the histogenesis and nomenclature of squamous cell carcinomas of the oesophagus with spindle cell elements. These tumours, many of which are polypoid, have been variously called carcinosarcoma, pseudosarcoma and polypoid carcinoma of the oesophagus. A study of three recent cases strongly supports the theory that these tumours are squamous cell carcinomas with spindle cell metaplasia. They are not necessarily polypoid and adenocarcinomatous elements may also be present.     

Ki-67表达与乳腺癌分子分型及临床病理特征的关系

目的：观察不同分子亚型乳腺癌中Ki-67的表达及其与乳腺癌临床病理特征的关系及意义。方法采用免疫组化En-Vision两步法检测245例乳腺癌组织中ER、PR、HER-2及Ki-67的表达,并比较Ki-67表达与乳腺癌临床病理参数的关系。结果不同分子分型乳腺癌中Ki-67的增殖指数差异有统计学意义( P<0．05);有淋巴结转移及肿块较大者中Ki-67增殖指数高于无淋巴结转移及肿块较小者,ER、PR阳性者中Ki-67增殖指数低于ER、PR阴性者,差异有统计学意义;患者按中位年龄50岁进行分组时,≤50岁组与>50岁组的Ki-67增殖指数差异无统计学意义;患者按≤40岁及≥60岁分为年轻组及老年组时,年轻组Ki-67增殖指数明显高于老年组。结论 Ki-67在三阴型乳腺癌、年轻患者、伴腋窝淋巴结转移、肿块较大及ER、PR阴性组中的增殖指数较高。 Ki-67可作为判断乳腺癌预后的重要指标。     

Pulmonary adenocarcinoma with a micropapillary pattern: a clinicopathological, immunophenotypic and molecular analysis

Zhang J, Liang Z, Gao J, Luo Y & Liu T
(2011) Histopathology  59 , 1204–1214
Pulmonary adenocarcinoma with a micropapillary pattern: a clinicopathological, immunophenotypic and molecular analysis Aims: To investigate the clinicopathological and molecular characteristics, immunohistochemical profile and prognosis of pulmonary adenocarcinoma with a micropapillary pattern (MPPAC). Methods and results: Eight hundred and eighty‐six pulmonary adenocarcinomas were divided into two groups: micropapillary pattern (MPP)‐positive (≥1% MPP) (n = 246) and MPP‐negative (n = 640), and clinicopathological characteristics were analysed. Of these, 66 cases with extensive MPP (MPP ≥ 50%) were studied by immunohistochemistry for several markers, and mutational analysis of K‐ras and epidermal growth factor receptor (EGFR) with the Scorpion Amplification Refractory Mutation System. Smoking, TNM stage, lymph node metastasis, lymphatic invasion, venous invasion, pleural invasion and differentiation grade were significantly associated with the prognosis of MPPAC (P < 0.05). Immunohistochemically, the positive rate in the MPP‐positive group was 100% for E‐cadherin, 100% for β‐catenin, 93.9% for Muc‐1, 57.6% for EGFR, 37.9% for p53, and 95.5% for Ki67. No differences were identified between MPP and non‐MPP tissue within the same tumour with regard to K‐ras and EGFR mutations. The 5‐year survival rates of patients were significantly different between the MPP‐positive group and the MPP‐negative group (P = 0.005). By multivariate analysis, a MPP was an independent prognostic factor for lung adenocarcinomas. Conclusions: MPP represents a distinct histopathological variant with biological and prognostic significance.     

Expression of molecular factors correlated with metastasis in small cell lung cancer and their significance

Distant metastasis continues to be a fatal threat to quality of life in patients with small cell lung caner (SCLC). The purpose of this work is to analyze the expressions of chemokine receptor four (CXCR4), matrix metalloproteinase-9 (MMP-9), transforming growth factor-b1 (TGF-β1), N-cadherin and vascular endothelial growth factor (VEGF) in small cell lung caner (SCLC), and to explore their correlations with the prognosis and metastasis. Sixty-five consecutive patients with stage I-III SCLC who received operation in our hospital from Jan 2003 to Oct 2009 were retrospectively analyzed. The expression of CXCR4 was found significantly correlated with bone metastasis (P = 0.004), and were marginally correlated with brain metastasis (P = 0.068) and lymph node metastasis (P = 0.085). The expression of MMP-9 was significantly associated with pathological staging (P = 0.048). Univariate analysis suggested surgical approach, clinical stage, lymph node metastasis were significantly associated with OS and PFS (P < 0.05), high expression of CXCR4 was significantly correlated with worse OS (P = 0.004) and PFS (P = 0.005). Multivariate analysis suggested surgical approach, TGF-β1, CXCR4 and lymph node metastasis were independent prognostic factor for PFS. In conclusion, High expression of CXCR4, MMP-9, TGF-β1 and VEGF were found in SCLC. High expression of MMP-9 was significantly associated with pathological staging, and high expression of CXCR4 was correlated with bone metastasis and also might correlate with brain metastasis. CXCR4 were independent prognostic factor for survival in SCLC and expanded samples should be further explored in the future.     

乳腺伴梭形细胞化生腺癌2例及文献复习

目的 探讨乳腺伴梭形细胞化生腺癌的临床病理特点及鉴别诊断要点。方法 复习2例乳腺伴梭形细胞化生腺癌的临床资料,并行免疫组化标记。结果 组织学特点：癌组织由梭形细胞构成,细胞异型不明显,核分裂象不多,呈片巢状、条索状、编织状排列,梭形细胞内可见腺癌的管状成分。免疫组化染色显示：癌细胞呈上皮性免疫表型,CK(pan)、EMA阳性,ER、PR、C—erbB-2常阴性,不表达S-100蛋白、desmin和vimentin。结论 乳腺伴梭形细胞分化的腺癌是上皮性特殊性乳腺癌中乳腺化生性癌的1种,其诊断主要依靠组织病理学及免疫组化标记。     

Clear cell metaplasia of the breast: a lesion showing eccrine differentiation

Clear cell metaplasia of the human breast is known to be a benign metaplastic change which has no pre-malignant connotation. Despite its proposed relationship to focal lactational change and to lactating breast, morphological and immunocytochemical features failed to demonstrate a clear relationship between these. Mucin secretion showed a characteristic pattern of granularity, and endocrine differentiation was not present. The mucin and immunocytochemical features suggest a relationship with eccrine sweat glands and a better name would perhaps be 'eccrine metaplasia' to underline the special relationship breast metaplasias have to sweat gland epithelium.     

15例具有血管周上皮样细胞分化的肿瘤临床病理分析

目的探讨具有血管周上皮样细胞分化的肿瘤(perivascular epithelioid cell tumor,PEComa)临床病理特征及免疫表型。方法对15例PEComa行EnVision两步法免疫组化及特殊染色,并分析其临床表现、病理学特征和免疫组化特点。结果 15例PEComa中13例为女性,且术后无复发。肿瘤可发生在身体任何部位,以肝脏和肾脏最多见,有包膜,多为实性,可有出血。特征性组织学改变是肿瘤细胞围绕血管生长。PAS染色显示该肿瘤细胞中有糖原物质沉积,弹力纤维染色显示该肿瘤中的血管壁缺乏弹力层。免疫组化显示所有PEComa病例均明显表达HMB-45、Melan-A、SMA,Ki-67阳性率不高。结论 PEComa是一组具有恶性潜能的肿瘤,多发于女性,来源于血管周上皮样细胞。大部分肿瘤呈良性过程,生物学分级极低,预后良好;极少部分病例可发生转移,预后不佳。免疫组化检测对其组织来源、生物学行为具有提示意义,并可辅助诊断。     

Intraductal papillary neoplasms of the bile duct consist of two distinct types specifically associated with clinicopathological features and molecular phenotypes

Intraductal papillary neoplasm of the bile duct (IPNB) is a grossly visible papillary biliary neoplasm with morphological variations and occasional invasion. Recently a new classification of IPNB into type 1 and type 2 was proposed in which the type 1 IPNBs consist of fine papillary neoplastic glands and the type 2 IPNBs consist of complex branching glands, seldom with foci of solid-tubular components. However, clinicopathological and molecular characteristics of these types of IPNBs are yet to be identified. We aimed to uncover clinicopathological and molecular characteristics of the types of IPNBs. Thirty-six IPNBs were studied retrospectively. Clinicopathological features as well as molecular alterations of 31 genes were evaluated by means of targeted next-generation sequencing and immunohistochemical examination of expression of mucin and cancer-associated molecules. The 36 IPNBs were classified into 22 of type 1 and 14 of type 2. The type 1 IPNBs were associated with a non-invasive phenotype, intestinal and oncocytic subtypes, development in the intrahepatic bile duct, overt mucin production, and a relatively good prognosis. The type 2 IPNBs were associated with an invasive phenotype, the pancreatobiliary subtype, development within the extrahepatic bile duct, and worse prognosis compared with the type 1 IPNBs. In the molecular analysis, recurrent mutations were found in TP53 (34.3%), KRAS (31.4%), STK11 (25.7%), CTNNB1 (17.1%), APC (14.3%), SMAD4 (14.3%), GNAS (11.4%), PBRM1 (11.4%), ELF3 (8.6%), KMT2C (8.6%), NF1 (8.6%), PIK3CA (8.6%), ARID1A (5.7%), ARID2 (5.7%), BAP1 (5.7%), BRAF (5.7%), EPHA6 (5.7%), ERBB2 (5.7%), ERBB3 (5.7%), KMT2D (5.7%), and RNF43 (5.7%). Mutations in KRAS and GNAS were enriched in the type 1 IPNBs, whereas mutations in TP53, SMAD4, and KMT2C were enriched in the type 2 IPNBs. These results indicate that IPNBs consist of two distinct types of neoplasms specifically associated with clinicopathological features and molecular phenotypes. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.