Human pathology最新文献

Objective

While human epidermal growth factor receptor 2 (HER2) is upregulated in endometrial carcinoma—especially in the p53 aberrant type— conventional anti-HER2 therapy is not typically used for this cancer type. Recently, HER2-targeted antibody-drug conjugates have shown antitumor effects against HER2 low-expressing cancers. Therefore, we analyzed the clinicopathological characteristics of HER2-positive endometrial carcinomas including those with low expression, as well as the prognostic significance of p53 and HER2 co-expression.

Methods

Immunohistochemistry for HER2 and p53 was performed in 530 patients with endometrial carcinoma; 124 cases (23%) were HER2-positive.

Results

Of the HER2-positive cases, >50% were 1+. A high prevalence of HER2 expression was observed in serous (64%), clear-cell (73%), and mixed (64%) carcinomas. Notably, 19% of endometrioid carcinomas were HER2-positive. HER2 positivity was significantly associated with age ≥60 years, high-grade histological subtype, deep myometrium invasion, stage III/IV, recurrence, and death. Univariate analysis showed that HER2-positive cases had reduced progression-free survival (PFS) (p = 0.007) and overall survival (OS) (p = 0.012). However, after adjusting for stage, HER2 positivity was not associated with survival. In the early stage, co-expression of HER2-positive and p53 aberrant types was associated with shorter PFS (p < 0.001) and OS (p < 0.001) compared with at least one negative result. Multivariate analysis of PFS showed HER2 and p53 co-expression (hazard ratio, 1.891; 95% confidence interval, 1.183–5.971, p = 0.008) as an independent prognostic factor.

Conclusions

This study presents detailed clinicopathological characteristics and the prognostic impact of HER2-positivity in endometrial carcinomas. HER2-targeted antibody-drug conjugate therapy may be broadly applicable to endometrial carcinoma.

We present a series of 9 follicular lymphomas that progressed/transformed into classical Hodgkin lymphoma (CHL). Three cases of CHL showed a syncytial pattern (SCHL) making the differential diagnosis to Gray zone lymphoma (GZL) challenging. None of these three cases presented in the mediastinum. Based in all molecular data analyzed (BCL2/BCL6 FISH studies, IgH PCR and TNGS with a customized gene panel) we did find clonal relationship between the BCL2-positive FL cases and their CHL components in all cases. The three SCHL/GZL cases showed an activated phenotype according to Hans algorithm, presented the t(14; 18)(q32; q21), two out of three showed B cell markers and all expressed CD30 and p53. Interestingly, we identified three BCL2-negative FL cases with a further diagnosis of CHL expanding the spectrum of these association. In one of these three cases a different mutational profile was found in both the FL and the CHL components. All this data together suggests that CHL associated to BCL2-positive FL could be originated in a common progenitor cell (CPC) that give rise to both FL and CHL, acquiring this last component further genetic events in a linear fashion. On the other hand, no clonal relationship between CHL and BCL2-negative FL could be found, suggesting a fortuity association. Nevertheless, ample series of cases studied with more sensitive techniques are needed to confirm our hypothesis.

Since the concept of IgG4-related disease (IgG4-RD) was proposed, that diagnosis has been considered in idiopathic fibroinflammatory diseases in various organs, particularly in cases with multi-organ involvement. We have recently encountered three cases of fibrosing disease of uncertain etiology with shared microscopic appearances. Case 1 (56-year-old man) had an irregular mass at the base of mesentery. Case 2 (29-year-old woman) presented with obstructive jaundice due to an ill-defined mass at the hepatic hilum and two lung nodules. Case 3 (53-year-old man) had multiple solid nodules in the mediastinum, peritoneum, retroperitoneum, and mesentery; he also had diffuse irregular narrowing of the intra- and extra-hepatic bile ducts in keeping with sclerosing cholangitis. Serum IgG4 concentrations were not elevated. Biopsies from the nodular lesions showed extensive hyalinizing fibrosis with an only focal lymphoplasmacytic infiltrate. Thick collagenous bundles are arranged in an irregular or partly whorl pattern. Typical storiform fibrosis or obliterative phlebitis was not observed. The number of IgG4-positive plasma cells was <10 cells/high-power field; the ratio of IgG4/IgG-positive plasma cells was <30%. After the histological diagnosis of sclerosing mesenteritis, pulmonary hyalinizing granuloma, and mediastinal fibrosis was made, they were treated with a trial of steroids, but none showed a significant response. In conclusion, a hyalinizing fibrotic condition can occur at various anatomical sites. They have shared microscopic findings, and are steroid-resistant. Although the clinical presentation may mimic IgG4-RD, the two conditions are likely distinct. We would propose a diagnostic term of ‘idiopathic hyalinizing fibrosclerosis’ for this under-recognized, rare, systemic condition.

The impact of special histological types (ST) in triple-negative breast cancer (TNBC) and its association with overall outcome has gained increasing relevance as survival has been linked to specific histological TNBC subtypes. We evaluated the clinicopathological and survival data of 598 patients with 613 TNBCs, including 464 TNBCs of no special type (NST) and 149 TNBCs ST (low-grade, n = 12, 8.1%; high-grade, n = 112, 75.2%; apocrine and androgen receptor-positive [APO AR], n = 25, 16.8%). Patients with low-grade TNBC ST and TNBC ST APO AR were significantly older (P < 0.001) and had a lower Ki67 index (P < 0.001) than those with TNBC NST. Patients with high-grade TNBC ST were significantly older (P = 0.006) and had poorer pathological responses to neoadjuvant chemotherapy (NAC) (P < 0.001) than those with TNBC NST. Significant survival differences were observed between low-grade TNBC ST, TNBC ST APO AR, high-grade TNBC ST, and TNBC NST in the entire study group (DFS, P = 0.002; DDFS, P = 0.001) and in the non-NAC subgroup (OS, P = 0.034; DFS, P = 0.001; DDFS, P < 0.001). Patients with low-grade TNBC ST had the best survival outcomes. Patients with high-grade TNBC ST showed significantly worse outcomes than those with TNBC NST (entire study group: OS, P = 0.049; DFS, P < 0.001; DDFS, P = 0.001; non-NAC subgroup: OS, P = 0.014; DFS, P < 0.001; DDFS, P < 0.001). We conclude that prognostic stratification of TNBC ST is ultimately important for optimizing the therapeutic management of patients with these rare tumor entities.

Tumors with pathogenic DICER1 mutation are rare and encompass sporadic or hereditary benign, intermediate and malignant tumors. DICER1-associated sarcomas are heterogeneous; however, the prototypical ones in the GYN-tract include embryonal rhabdomyosarcoma, adenosarcoma and moderately to poorly differentiated Sertoli-Leydig tumor. In this report, we present three unique uterine sarcomas with DICER1 mutation and remarkable diffuse round/spindle cell morphology. The tumors occurred in cervix (n = 1), and uterine corpus (n = 2). The patient ages were 30, 37 and 59 years with tumor size of 8.8, 10 and 8.6 cm, respectively. Morphologically all three tumors were characterized by distinct spindle/round cell morphology and various amounts of neuroectodermal differentiation (yolk sac-like tubules, blastomatous areas and rosette formation). Other morphologic features of DICER1-sarcoma reported in the literature including cambium layer, focal or diffuse anaplasia, solid and cystic architecture, and chondroid/osteoid areas were absent. All three sarcomas were positive for SALL4 and had variable neuroendocrine marker expression. Whole genome methylation analysis was performed on one of the uterine sarcomas, which clustered the tumor with embryonal tumor with multilayered rosettes. Follow up information was available on all three cases. Two patients were alive with no evidence of disease 13 and 14 months post operation, while one patient had imaging evidence of local recurrence 4 months post operation. In summary, we describe three unique DICER1-sarcomas and expand the phenotypic spectrum of this emerging entity, particularly with GYN-tract origin.

Anaplastic lymphoma kinase-positive histiocytosis, first reported in 2008, is a rare, novel type of neoplasm. To date, no more than 100 cases of anaplastic lymphoma kinase-positive histiocytosis have been reported. In this retrospective study, 12 cases of anaplastic lymphoma kinase-positive histiocytosis, including clinical symptoms, histological features, molecular pathology, treatment, and prognosis, in children were analyzed to gain a deeper understanding of the disease. All patients were Asian children, aged 2 months to 8 years and 2 months (mean 3.1 years), and the male-to-female ratio was 5:7. All patients were followed up closely. One patient died during the follow-up period, seven (case 1–7) had focal anaplastic lymphoma kinase-positive histiocytosis, and five (case 8–12) had multisystem anaplastic lymphoma kinase-positive histiocytosis. In addition, we report the case of a patient who benefited from anaplastic lymphoma kinase-targeted therapy and a patient with the rare EML4-ALK fusion gene. The current study is expected to substantially contribute to increasing the awareness of anaplastic lymphoma kinase-positive histiocytosis.

Four primary extraskeletal osteosarcomas of the pleura are presented. The patients were men between the ages of 63 and 78 years (average: 70.5 years) who presented with symptoms of chest pain, cough, and shortness of breath. Diagnostic imaging showed variably calcified, pleural-based masses and/or diffuse pleural thickening, clinically mimicking mesothelioma. Thoracoscopic surgical material was obtained for histopathological diagnosis. Histological findings showed the presence of a neoplastic spindle cell proliferation composed of fusiform cells with scant cytoplasm, elongated nuclei and inconspicuous nucleoli. Mitotic activity was easily identified. Additionally, all tumors showed extensive osseous differentiation in the form of osteoid matrix production; one tumor demonstrated additional chondrosarcomatous elements and another showed focal myxoid changes. Immunohistochemical analysis revealed that the tumor cells were uniformly negative for a wide variety of antibodies, including keratin AE1/AE3, keratin 5/6, D2-40, EMA, calretinin, WT-1, BerEP4, and HEG1; BAP1 was retained in all cases. In addition, fluorescence in situ hybridization for CDKN2A (p16) was negative for homozygous deletion in all tumors. Clinical follow-up showed that one patient had died 8 months after diagnosis and one had remained alive with short post-diagnostic follow-up. The tumors herein described highlight a challenging issue in the separation of mesothelioma with heterologous elements from true osteosarcomas of pleural origin. We propose that a diagnosis of extraskeletal osteosarcoma of the pleura is rendered for tumors with malignant osseous and/or cartilaginous differentiation in which comprehensive immunohistochemical studies and FISH analysis have failed to provide support for a diagnosis of mesothelioma with heterologous elements.

Purpose

No consensus on the definition of right and left colorectal cancer (CRC) exists, nor studies offering histological or molecular basis for such categorisation. This study investigated the regional variations in the histological and molecular characteristics of CRCs, with the objective of determining an optimal division point between right and left CRCs.

Materials and methods

An observational study of consecutive patients who underwent CRC resection (1995–2022) at Concord Hospital, Sydney was performed. Clinicopathological data were extracted from a prospective database and seven permutations of right-left divisions considered. Logistic regression tested association between the right-left divisions and pathological characteristics. Receiver operating characteristic and area under the curve (AUC) analyses determined the discriminative ability of each division to predict 18 pathology characteristics.

Results

3753 patients underwent a CRC resection (2120 male; mean 69.5yrs [SD12.6]). There was regional variation in tumours with respect to tumour infiltrating lymphocytes (TILs), mismatch repair deficiency (dMMR), and mutant BRAF (mBRAF). Left-sided tumours were less likely to demonstrate TILs (P < 0.001), be dMMR (P < 0.001), and express mBRAF (P < 0.001). Division at the descending-sigmoid junction yielded highest discriminative abilities: TILs – AUC 0.66, dMMR – AUC 0.76, and mBRAF – AUC 0.73.

Conclusion

This is the first study to provide a pathological basis on which right- and left-sided cancers may be defined, and found the optimal division point between the right and left colorectum to be at the descending-sigmoid junction. Further research is needed to determine whether this can facilitate individualised patient management.