Human pathology最新文献

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Ductal hamartoma of the pancreas: A clinicopathologic study. 胰腺导管火腿肠瘤：临床病理学研究

IF 2.7 2区医学 Q2 PATHOLOGY

Human pathology

Pub Date : 2024-10-01 DOI: 10.1016/j.humpath.2024.105669

Debasmita Das, Ivan A Gonzalez, Matthew M Yeh, Tsung-Teh Wu, Dhanpat Jain

Background: Benign ductular proliferative lesions that resemble hepatic von-Meyenburg Complexes(VMC)/bile duct hamartomas have been noted to occur in the pancreas, but their incidence, clinicopathologic features and pathogenesis remains unknown. We present herein 3 patients that presented as cysts and call them pancreatic ductal hamartomas (PDH).

Methods: Three cases of PDH were identified form a multi-institutional collaborative group, and their clinicopathological were reviewed. In addition, we also examined 115 consecutive pancreatic resections at our institutions for the presence of incidental PDHs.

Results: The lesions were detected in each case during imaging for abdominal symptoms or grossing. The clinical suspicion was intra-ductal pancreatic mucinous cystic neoplasm (IPMN) in each case that led to pancreatectomy. The cyst fluid CEA was elevated in 2 of the patients tested. The patient age and gender were 73/M (case1), 68/F (case2) and 73/M (case3). In case1 besides the larger cystic lesion, numerous tiny lesions (0.1-0.3 cm) were seen throughout the pancreas. In case2 this was the only lesion, while in case3 there was another gastric-type IPMN with high-grade dysplasia. PDH were identified in 5(4.3%) of 115 consecutive pancreatectomy specimens. The PDHs measured 0.1-2.3 cm, and the histology is characterized by proliferation of irregular ductal structures lined by bland flattened to low columnar epithelium, variable cystic change and inspissated luminal secretions. The lining epithelium varied from non-mucinous pancreatico-biliary type to mucinous gastric foveolar-type, with occasional squamous metaplasia.

Summary: PDH are seen in 4.5% of all pancreatectomy specimens and detected incidentally, but occasionally may become large and/or cystic enough leading to pancreatectomy. Their relationship to pancreatic carcinoma or IPMN remains currently unknown.

背景：已注意到胰腺中存在类似肝脏von-Meyenburg复合体（VMC）/胆管火腿状瘤的良性导管增生性病变，但其发病率、临床病理特征和发病机制仍不清楚。我们在此介绍3例表现为囊肿的患者，并将其称为胰管火腿肠瘤（PDH）：方法：我们在一个多机构合作小组中发现了三例 PDH 病例，并对其临床病理进行了回顾。此外，我们还对本机构的 115 例连续胰腺切除术进行了检查，以发现偶然出现的 PDH：每个病例都是在腹部症状或大体检查时发现病变的。临床上怀疑每例病例均为胰腺导管内粘液性囊肿（IPMN），因此进行了胰腺切除术。在接受检测的患者中，有 2 人的囊液 CEA 升高。患者的年龄和性别分别为 73/M（病例 1）、68/F（病例 2）和 73/M（病例 3）。在病例 1 中，除了较大的囊性病变外，整个胰腺还可见许多微小病变（0.1-0.3 厘米）。在病例 2 中，这是唯一的病变，而在病例 3 中，则有另一个胃型 IPMN，并伴有高度发育不良。在 115 例连续的胰腺切除标本中，有 5 例（4.3%）发现了 PDH。PDH的大小为0.1-2.3厘米，组织学特征为不规则导管结构增生，内衬平滑扁平至低柱状上皮，有不同程度的囊性改变和管腔分泌物。内衬上皮从非粘液性胰胆管型到粘液性胃窝型不等，偶有鳞状化生。小结：PDH 见于所有胰腺切除术标本的 4.5%，偶然被发现，但偶尔也会变大和/或囊变，导致胰腺切除术。它们与胰腺癌或 IPMN 的关系目前仍不清楚。

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引用次数: 0

Pure intertubular seminoma (PITS) of the testis: A multi-institutional cohort of a rare growth pattern of seminoma 睾丸纯输精管间精原细胞瘤（PITS）：一种罕见精原细胞瘤生长模式的多机构队列。

IF 2.7 2区医学 Q2 PATHOLOGY

Human pathology

Pub Date : 2024-09-19 DOI: 10.1016/j.humpath.2024.105667

Pure intertubular seminoma (PITS) of the testis is described as the presence of seminoma cells within the interstitium of testis without any evidence of diffuse growth pattern or mass lesion of classical seminoma. These tumors are clinically and grossly inconspicuous and are diagnosed incidentally or during investigations for testicular pain, infertility or other symptoms. Rarely metastasis is the first presentation. Microscopic identification can be difficult and poses a diagnostic challenge in the absence of a mass lesion. Seminomas with exclusive intertubular growth patterns were gathered in an international cohort. Diagnoses were confirmed by fellowship-trained or specialized urologic pathologists. Cases with the presence of a classical diffuse or nested pattern of seminoma or any other germ cell tumor component were excluded. The patient's age, tumor characteristics and additional clinicopathologic features were recorded and analyzed. 15 patients of pure intertubular seminoma (PITS) were collated. The mean age of presentation was 29 years. Patients presented with variable symptoms, including undescended testis (26%, n = 4/15), testicular heaviness/pain (20%, n = 3/15) infertility (20%, n = 3/15) and metastasis (6%, n = 1/15); presentation was unknown in 4 patients. Of note, none of the patients presented because of testicular mass. Serum markers were within normal limits in most patients (93%, n = 14/15) with available data. No tumors were identified macroscopically; however, an ill-defined, grey-white, firm area was noted in one orchiectomy specimen. Microscopically, tumor cells were seen in intertubular spaces as dispersed individual cells or small clusters. Tumor cells were round to polygonal with large nuclei and prominent nucleoli. Mild to moderate lymphocytic infiltrates were seen admixed with tumor cells in 40% (n = 6/15) of the tumors. GCNIS was present in association with most PITS (73%, n = 11/15). Tubular atrophy with thickening of the basement membrane and Leydig cell hyperplasia was observed in one tumor. Thirty-three percent (n = 5/15) of the tumors showed pagetoid involvement of rete testis, including the tumor with metastasis. All tumors showed the classical immunohistochemical profile of seminoma, with PLAP, c-KIT, OCT3/4, D2-40 and SALL4 positivity. PITS can be clinically & pathologically inconspicuous, difficult to stage and liable to be misdiagnosed especially if presented with metastasis. Despite the inconspicuousness, PITS may represent an aggressive growth pattern of seminoma with the propensity for rete testis invasion.

睾丸纯管间精原细胞瘤（PITS）是指睾丸间质内存在精原细胞瘤细胞，但无任何弥漫生长模式或典型精原细胞瘤肿块病变的证据。这些肿瘤在临床上和大体上都不明显，是在偶然情况下或因睾丸疼痛、不育或其他症状进行检查时被诊断出来的。很少以转移为首发症状。显微镜下的鉴别可能比较困难，在没有肿块病变的情况下会给诊断带来挑战。我们在一个国际队列中收集了具有独特管间生长模式的精原细胞瘤。诊断由接受过研究员培训或专业的泌尿科病理学家确认。存在典型弥漫或巢状精原细胞瘤或任何其他生殖细胞肿瘤成分的病例均被排除在外。对患者的年龄、肿瘤特征和其他临床病理特征进行了记录和分析。共收集整理了15例纯管间精原细胞瘤（PITS）患者。患者的平均年龄为29岁。患者的症状不一，包括睾丸下降（26%，n=4/15）、睾丸沉重/疼痛（20%，n=3/15）、不育（20%，n=3/15）和转移（6%，n=1/15）；4名患者的症状不明。值得注意的是，没有一名患者因睾丸肿块而就诊。大多数患者（93%，n=14/15）的血清标志物在正常范围内。宏观上未发现肿瘤，但在一份睾丸切除术标本中发现一个界限不清的灰白色坚实区域。显微镜下，肿瘤细胞以分散的单个细胞或小细胞簇的形式出现在管间隙中。肿瘤细胞呈圆形至多边形，核大，核仁突出。40%的肿瘤（n=6/15）中可见轻度至中度淋巴细胞浸润，与肿瘤细胞混杂在一起。大多数 PITS（73%，n=11/15）伴有 GCNIS。在一个肿瘤中观察到肾小管萎缩、基底膜增厚和莱狄格细胞增生。33%的肿瘤（n=5/15）显示睾丸前叶受累，其中包括有转移的肿瘤。所有肿瘤均显示精原细胞瘤的典型免疫组化特征，PLAP、c-KIT、OCT3/4、D2-40 和 SALL4 阳性。PITS 在临床和病理上都不明显，难以分期，容易误诊，尤其是在出现转移的情况下。尽管不明显，但PITS可能代表了精原细胞瘤的一种侵袭性生长模式，具有侵犯睾丸前叶的倾向。

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引用次数: 0

Inside front cover - Masthead 封面内页 - 刊头

IF 2.7 2区医学 Q2 PATHOLOGY

Human pathology

Pub Date : 2024-09-12 DOI: 10.1016/S0046-8177(24)00167-9

引用次数: 0

Information for Authors 作者须知

IF 2.7 2区医学 Q2 PATHOLOGY

Human pathology

Pub Date : 2024-09-12 DOI: 10.1016/S0046-8177(24)00170-9

引用次数: 0

Expanding the spectrum of fusion partners for cystic TFE3-rearranged renal cell carcinomas: A report of a MAPK1IP1L::TFE3-rearranged renal cell carcinoma. 扩大囊性 TFE3 重组肾细胞癌融合伙伴的范围：一例MAPK1IP1L::TFE3重组肾细胞癌的报告。

IF 2.7 2区医学 Q2 PATHOLOGY

Human pathology

Pub Date : 2024-09-11 DOI: 10.1016/j.humpath.2024.105654

Burak Tekin, Ruqin Chen, Rumeal D Whaley, Jordan P Reynolds, Hussam Al-Kateb, John C Cheville, Sounak Gupta

引用次数: 0

Glutamine synthetase staining patterns in cirrhosis 肝硬化中的谷氨酰胺合成酶染色模式

IF 2.7 2区医学 Q2 PATHOLOGY

Human pathology

Pub Date : 2024-09-06 DOI: 10.1016/j.humpath.2024.105655

Advanced liver fibrosis can regress following the elimination of causative injuries. Glutamine synthetase (GS) immunohistochemical expression is normally in centrizonal perivenular hepatocytes but can be present in periportal hepatocytes in cases of regressed cirrhosis. This study identified periportal staining and investigated the spectrum of GS staining patterns seen in a range of cirrhotic livers with varying disease processes. The hematoxylin and eosin and GS-stained slides of 88 liver resection/explant specimens with advanced fibrosis cases by different causes were reviewed, and trichrome and orcein stains were used to classify cases as progressive, indeterminate, or regressive. Periportal GS staining was seen in 97% of regressive cases and 84% progressive or indeterminate cases. Liver resection specimens with periportal GS staining showed a variety of patterns, including predominantly perivenular, predominantly periseptal, and perinodular staining. The GS periseptal pattern is more common in regressed cirrhosis compared to progressive cases. The perinodular staining was seen in 16 cases resulting from various etiologies, including biliary atresia, steatotic liver disease, primary biliary cholangitis, and viral hepatitis, 75% of which demonstrated cholestasis. This study further subclassified GS staining patterns of “periportal” pattern in cirrhotic liver. Compared to orcein/trichrome staining, GS immunohistochemical staining is not as useful in distinguishing regressed cases from non-regressed cases.

晚期肝纤维化可在消除致病损伤后消退。谷氨酰胺合成酶（GS）的免疫组化表达通常出现在中心区肝细胞周围，但在肝硬化消退的病例中也可能出现在肝门周围。本研究确定了肝门周围染色，并调查了一系列不同疾病过程的肝硬化患者肝脏中的 GS 染色模式谱。研究人员对88例不同病因导致的晚期肝纤维化肝切除/移植标本的苏木精、伊红和GS染色切片进行了回顾性分析，并使用三色染色和orcein染色将病例分为进展型、不确定型和退变型。97%的退行性病例和84%的进展性或不确定病例可见门脉周围GS染色。有门静脉周围GS染色的肝切除标本显示出多种模式，包括主要为肝周、主要为肝周及结节周围染色。与进展期病例相比，GS包膜染色在消退期肝硬化中更为常见。16例病因不同的病例出现了结节周围染色，包括胆道闭锁、脂肪肝、原发性胆汁性胆管炎和病毒性肝炎，其中75%的病例表现为胆汁淤积。这项研究将肝硬化肝脏的 GS 染色模式进一步细分为 "门脉周围 "模式。与orcein/trichrome染色法相比，GS免疫组化染色法在区分退行性病例和非退行性病例方面作用不大。

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引用次数: 0

Fluorescence in-situ hybridization assessment of spindle cell-rich testicular sex cord stromal tumors demonstrates multiple chromosomal gains across histologic subtypes 对富含纺锤细胞的睾丸性索间质瘤的荧光原位杂交评估显示不同组织学亚型存在多种染色体增益。

IF 2.7 2区医学 Q2 PATHOLOGY

Human pathology

Pub Date : 2024-08-30 DOI: 10.1016/j.humpath.2024.105652

Spindle cell-rich testicular sex cord-stromal tumors (TSCSTs) comprise a group that includes mostly (but not exclusively): myoid gonadal stromal tumor (MGST), adult granulosa cell tumor (AGCT), and unclassified TSCST. These entities demonstrate histopathologic overlap, and prior genomic studies have failed to identify specific oncogenic drivers. Results of DNA sequencing suggest that different types of spindle cell-rich TSCSTs harbor a recurrent pattern of chromosomal gains. However, these results have not been validated by alternative methods and the extent of these changes within individual tumors remains unknown. We used a combination of commercially available fluorescence in-situ hybridization (FISH) probes (3q11.2, 6p24.3, 6q11.1, 6q23, 7q11.21-q11.22, 9p21.3, 11q13.3, 17p11.2) to enumerate a subset of chromosomes identified as altered (gained) in prior studies. We analyzed 10 cases (3 MGST, 4 unclassified TSCST, 3 AGCT), including 7 that had been previously sequenced. FISH demonstrated gains of chromosomes 3, 6, 7, 9, and 11 above the pre-established threshold (25%) in 50%, 80%, 70%, 20%, and 40% of cases, respectively, with gains of chromosome 17 being present in only 1 unclassified TSCST. The proportion of cells with chromosomal gains ranged from 26% to 60%. Tumors with available copy number data from prior genomic analyses showed a partial discordance between FISH and sequencing results. This study demonstrates that spindle-cell rich TSCSTs harbor a recurrent pattern of chromosomal gains, which are present in variable subsets of neoplastic cells. Further studies are needed to determine if these chromosomal changes represent a mechanism relevant for oncogenesis or a secondary event.

富含纺锤细胞的睾丸性索间质瘤（TSCST）主要包括（但不限于）：肌样性腺间质瘤（MGST）、成人颗粒细胞瘤（AGCT）和未分类的 TSCST。这些实体在组织病理学上存在重叠，而之前的基因组研究却未能发现特定的致癌驱动因素。DNA测序结果表明，不同类型的富含纺锤体细胞的TSCST蕴藏着一种染色体增益的复发性模式，与倍性的转变相一致。然而，这些结果尚未得到其他方法的验证，而且这些变化在单个肿瘤中的程度仍然未知。我们使用市售的荧光原位杂交（FISH）探针（3q11.2、6p24.3、6q11.1、6q23、7q11.21-q11.22、9p21.3、11q13.3、17p11.2）组合，对先前研究中确定为染色体改变（增益）的染色体子集进行了计数。我们分析了 10 个病例（3 个 MGST、4 个未分类的 TSCST、3 个 AGCT），其中 7 个病例之前已进行过测序。FISH显示，分别有50%、80%、70%、20%和40%的病例中3、6、7、9和11号染色体的增益超过了预先设定的阈值（25%），只有1例未经分类的TSCST存在17号染色体的增益。染色体增益的细胞比例从 26% 到 60% 不等。通过先前的基因组分析获得拷贝数数据的肿瘤显示，FISH 和测序结果存在部分不一致。这项研究表明，富含纺锤形细胞的 TSCST 存在染色体增益的复发性模式，这些增益存在于不同的肿瘤细胞亚群中。要确定这些染色体变化是一种致癌机制还是一种继发性事件，还需要进一步的研究。

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引用次数: 0

Hairy cell leukemia with an atypical extranodal presentation: A clinicopathological analysis of four cases 非典型结节外表现的毛细胞白血病：四例病例的临床病理分析

IF 2.7 2区医学 Q2 PATHOLOGY

Human pathology

Pub Date : 2024-08-28 DOI: 10.1016/j.humpath.2024.105651

引用次数: 0

Gradual telomere shortening in the tumorigenesis of pancreatic and hepatic mucinous cystic neoplasms 胰腺和肝脏粘液性囊肿肿瘤发生过程中端粒的逐渐缩短

IF 2.7 2区医学 Q2 PATHOLOGY

Human pathology

Pub Date : 2024-08-28 DOI: 10.1016/j.humpath.2024.105653

Mucinous cystic neoplasm (MCN) is one of the precursor lesions of pancreatic ductal adenocarcinoma and intrahepatic cholangiocarcinoma. The aim of this study is to examine the presence of short telomeres in promoting the tumorigenesis of MCN by measuring telomere lengths in distinct components of MCN, including the mucinous lining epithelium, non-mucinous lining epithelium, and ovarian-type stroma. A total of 45 patients with MCN (30 pancreatic and 15 hepatic cases) were obtained. Quantitative telomere-specific fluorescent in situ hybridization was performed to measure the telomere length of specific cell types within MCNs, including mucinous lining epithelium, non-mucinous lining epithelium, and ovarian-type stroma, as well as normal ductal epithelium and adenocarcinoma. Relative telomere lengths tended to decrease between normal ductal epithelium, ovarian-type stroma, non-mucinous lining epithelium, mucinous lining epithelium, and adenocarcinoma regardless of the involved organs. Among the analyzed cell types, relative telomere lengths were significantly different between normal ductal epithelium (3.31 ± 0.78), ovarian-type stroma (2.90 ± 0.93), non-mucinous lining epithelium (2.84 ± 0.79), mucinous lining epithelium (2.49 ± 0.93), and adenocarcinoma (1.19 ± 0.59), respectively (P < 0.001, mixed-effects model). As expected, no difference in relative telomere lengths was observed between normal ductal epithelium and ovarian-type stroma; however, significant differences were observed in pair-wise comparisons between ovarian-type stroma vs. non-mucinous lining epithelium (P = 0.001), non-mucinous lining epithelium vs. mucinous lining epithelium (P = 0.005), and mucinous lining epithelium vs. adenocarcinoma (P < 0.001). These findings suggest gradual telomere shortening occurs in the tumorigenesis of MCN, which may have important implications for the progression of this disease.

粘液性囊性肿瘤（MCN）是胰腺导管腺癌和肝内胆管癌的前驱病变之一。本研究旨在通过测量MCN不同组成部分（包括粘液性内膜上皮、非粘液性内膜上皮和卵巢型基质）的端粒长度，研究短端粒在促进MCN肿瘤发生中的作用。该研究共收集了 45 例 MCN 患者（30 例胰腺癌患者和 15 例肝癌患者）的数据。采用定量端粒特异性荧光原位杂交技术测量了MCN中特定细胞类型的端粒长度，包括粘液性内膜上皮、非粘液性内膜上皮和卵巢型基质，以及正常导管上皮和腺癌。无论涉及哪个器官，正常导管上皮、卵巢型基质、非粘液性内膜上皮、粘液性内膜上皮和腺癌之间的相对端粒长度都呈下降趋势。在分析的细胞类型中，正常导管上皮（3.31 ± 0.78）、卵巢型基质（2.90 ± 0.93）、非粘液性内膜上皮（2.84 ± 0.79）、粘液性内膜上皮（2.49 ± 0.93）和腺癌（1.19 ± 0.59）之间的相对端粒长度分别存在显著差异（P < 0.001，混合效应模型）。不出所料，正常导管上皮与卵巢型基质之间的相对端粒长度没有差异；但在卵巢型基质与非粘液性内膜上皮（P = 0.001）、非粘液性内膜上皮与粘液性内膜上皮（P = 0.005）以及粘液性内膜上皮与腺癌（P <0.001）之间的成对比较中观察到显著差异。这些发现表明，端粒逐渐缩短发生在MCN的肿瘤发生过程中，这可能对该疾病的进展有重要影响。

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引用次数: 0

Genomic analysis reveals molecular characterization of CD30+ and CD30− extranodal natural killer/T-cell lymphomas (ENKTLs) 基因组分析揭示了CD30+和CD30-结节外自然杀伤/T细胞淋巴瘤（ENKTLs）的分子特征。

IF 2.7 2区医学 Q2 PATHOLOGY

Human pathology

Pub Date : 2024-08-24 DOI: 10.1016/j.humpath.2024.105650

Extranodal natural killer (NK)/T-cell lymphoma (ENKTL) is prevalent in the Asian population; however, little is known about its molecular characteristics. In this study, we examined the CD30 expression in ENKTLs and then performed whole exome sequencing on ten CD30⁺ ENKTL and CD30⁻ ENKTL paired samples. CD30 was positive in 55.74% of the ENKTLs. Single nucleotide and insertion/deletion polymorphism analyses revealed that 53.41% of the somatic mutations in CD30⁺ ENKTLs were shared with CD30⁻ ENKTLs, including mutations in SERPINA9, MEGF6, MUC6, and KDM5A. Frequently mutated genes were primarily associated with cell proliferation and migration, the tumor microenvironment, energy and metabolism, epigenetic modulators, vascular remodeling, and neurological function. PI3K-AKT, cAMP, cGMP-PKG, and AMPK pathways were enriched in both CD30⁺ and CD30⁻ ENKTLs. Copy number variation analysis identified a unique set of genes in CD30⁺ ENKTLs, including T-cell receptor genes (TRBV6-1 and TRBV8), cell cycle-related genes (MYC and CCND3), immune-related genes (GPS2, IFNA14, TTC38, and CTSV), and a large number of ubiquitination-related genes (USP32, TRIM23, TRIM2, DUSP7, and UBE2QL1). BCL10 mutation was identified in 6/10 CD30⁺ ENKTLs and 7/10 CD30⁻ ENKTLs. Immunohistochemical analysis revealed that the expression pattern of BCL10 in normal lymphoid tissues was similar to that of BCL2; however, its expression in ENKTL cells was significantly higher (67.92% vs. 16.98%), implying the potential application of BCL10 inhibitors for treating ENKTLs. These results provide new insights into the genetic characteristics of CD30⁺ and CD30⁻ ENKTLs, and could facilitate the clinical development of novel therapies for ENKTL.

结节外天然杀伤（NK）/T细胞淋巴瘤（ENKTL）在亚洲人群中很常见，但人们对其分子特征知之甚少。在这项研究中，我们检测了ENKTL中CD30的表达，然后对10个CD30+ ENKTL和CD30- ENKTL配对样本进行了全外显子组测序。55.74%的ENKTL中CD30呈阳性。单核苷酸和插入/缺失多态性分析表明，在CD30+ ENKTL中，53.41%的体细胞突变与CD30- ENKTL共享，包括SERPINA9、MEGF6、MUC6和KDM5A的突变。经常发生突变的基因主要与细胞增殖和迁移、肿瘤微环境、能量和新陈代谢、表观遗传调节剂、血管重塑和神经功能有关。PI3K-AKT、cAMP、cGMP-PKG和AMPK通路在CD30+和CD30-ENKTL中均有富集。拷贝数变异分析在CD30+ ENKTLs中发现了一组独特的基因，包括T细胞受体基因（TRBV6-1和TRBV8）、细胞周期相关基因（MYC和CCND3）、免疫相关基因（GPS2、IFNA14、TTC38和CTSV）以及大量泛素化相关基因（USP32、TRIM23、TRIM2、DUSP7和UBE2QL1）。在 6/10 例 CD30+ ENKTL 和 7/10 例 CD30- ENKTL 中发现了 BCL10 突变。免疫组化分析表明，BCL10在正常淋巴组织中的表达模式与BCL2相似，但在ENKTL细胞中的表达明显更高（67.92%对16.98%），这意味着BCL10抑制剂有可能用于治疗ENKTL。这些结果为了解CD30+和CD30-ENKTL的遗传特征提供了新的视角，有助于ENKTL新型疗法的临床开发。

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