Histological Growth Pattern Research Articles

The Great Mimicker: Goblet Cell Adenocarcinoma of the Appendix Mimicking Mammary Carcinoma in a Patient with a History of Metastatic Breast Cancer

Abstract Introduction/Objective Goblet cell adenocarcinoma of the appendix is a rare and aggressive malignancy with high- grade histological patterns that pose diagnostic challenges due to their resemblance to other tumors. Previous reports have indicated that high-grade goblet cell adenocarcinoma may exhibit similarities to well-differentiated neuroendocrine tumors, and metastatic high-grade goblet cell adenocarcinoma can manifest diverse histologic growth patterns within a single section. Methods/Case Report We present a case of an 82-year-old female with a known history of breast cancer with sacral metastasis, presenting with a left upper quadrant “pinching” sensation. Histopathological examination following colectomy showed features of metastatic mammary carcinoma with mixed lobular (pleomorphic and partial signet ring cell type) and ductal features (Figure 1); Notably, different histologic patterns were observed in two tumor deposits, highlighting the complexity of the diagnosis (Figure 2). However, further investigation of the tip of the appendix revealed goblet-like mucinous cells arranged in a tubular growth pattern (Figure 3). Immunohistochemical stains were performed with adequate controls, revealing positive staining for CK20, SATB2, and CDX2, while showing negativity for BRST2, SATB2, GATA3, CK7, PR, ER, and HER2 (Figure 4). These findings corroborate the diagnosis of goblet cell adenocarcinoma. Results (if a Case Study enter NA) NA Conclusion In our case, we observed morphological features of goblet cell adenocarcinoma that overlapped with those of established mammary carcinomas. This scenario underscores the diagnostic challenges posed by rare tumors and emphasizes the significance of identifying the low-grade component of goblet cell adenocarcinoma, particularly in patients with a history of metastatic breast cancer.

Beneath HMGA2 alterations in pleomorphic adenomas: Pathological, immunohistochemical, and molecular insights

AimsMost salivary gland neoplasms are distinguished by specific recurrent gene fusions. Recently, a subset of pleomorphic adenomas (PAs) originated from the parotid gland harboring the HMGA2:WIF1 fusion was described with a canalicular adenoma-like morphology and a greater propensity for recurrence and carcinomatous transformation. Methods and resultsThis study delineates the clinicopathological attributes of 54 cases of PAs exhibiting HMGA2 alterations, predominantly characterized by the HMGA2:WIF1 fusion, alongside a comparative analysis of their morphological and immunohistochemical profiles. The cohort consisted of 23 females and 31 males (n = 54), mean age was 56.7 (25–84), tumors predominantly originated from the parotid gland (94.4%, 51/54), with 3 cases from seromucous glands (5.6%). Mean tumor size was 2.6 cm (0.8–7.5). No clinical difference (demographic, follow-up) was observed among histological subsets (conventional, hybrid, and pure). Complete excision was performed in all cases, with follow-up data available for 41% (22/54) of patients, showing 13.6% of recurrence (3/22) between 5 and 8 months. Various histological growth patterns were identified, with the pure hypercellular monomorphic subset being the most prevalent. The HMGA2:WIF1 gene was identified in all subsets without any particular predominance. Novel gene partners of HMGA2 were identified, comprising NRXN1, INPP4B, MSRB3, PHLDA1, and FLJ41278. ConclusionsThe present study reports that the HMGA2:WIF1 gene fusion was present in all subsets of PAs without significant predominance. However, further investigations are warranted to explore the relationship between histological subsets of PAs and the molecular alterations underlying them.

Immunohistochemistry identifies E-cadherin, N-cadherin and focal adhesion kinase (FAK) as predictors of stage I non-small cell lung carcinoma spread through the air spaces (STAS), and the combinations as prognostic factors.

Spread through air spaces (STAS) is one of the multiple modes of lung cancer dissemination, yet its molecular and clinicopathological characterization remains poorly studied. This study aimed to investigate the effect of adhesion molecule expression levels on the incidence of STAS and postoperative recurrence in stage I lung cancer patients undergoing radical resection. E-cadherin, P-cadherin, N-cadherin, focal adhesion kinase (FAK), epithelial cell adhesion molecule (EpCAM), neural cell adhesion molecule 1 (NCAM1), vascular cell adhesion molecule 1 (VCAM1), intercellular cell adhesion molecule-1 (ICAM-1) were analyzed retrospectively using immunohistochemistry in patients undergoing radical resection for stage I non-small cell lung cancer (NSCLC). Patients were categorized into four groups based on adhesion molecule expression levels: "low/low", "high/low", "low/high", and "high/high", and the group with the lowest recurrence-free probability (RFP) was defined as high risk. Associations between those adhesion molecules' expression levels and STAS were determined by using the Chi-squared test and logistic regression model. RFP was analyzed by using the log-rank test and Cox proportional risk model. As of January 1, 2024, 12 of 60 patients undergoing radical resection for stage I lung carcinoma had a disease recurrence. All 60 patients' tissue specimens were retrospectively analyzed, and there were no significant differences between patients with STAS-positive (n=30) and STAS-negative (n=30) in baseline clinicopathologic features, except for histological growth patterns. We found that low expression of E-cadherin, high expression of N-cadherin and FAK, and males were independent predictors of higher incidence of STAS. Multivariate Cox analysis showed that tumors with low E-cadherin/high N-cadherin, low E-cadherin/high FAK, and high N-cadherin/high FAK expression were important predictors of recurrence in patients with stage I lung carcinoma. In addition, females and high N-cadherin/high FAK were associated with a high risk of recurrence in patients with STAS. E-cadherin, N-cadherin, and FAK are predictors of STAS occurrence in stage I NSCLC, and their combinations are prognostic factors. The discovery of these molecular markers provides clinicians with a reliable means that may help in the early identification of individuals with a higher risk of recurrence in lung cancer patients, targeting personalized treatment plans such as aggressive adjuvant therapy or closer follow-up.

Clinicopathologic Features of Gastrointestinal Tract Langerhans Cell Histiocytosis

Gastrointestinal (GI) tract involvement by Langerhans cell histiocytosis (LCH) is rare and its clinicopathologic characteristics have only been described in case reports and small series. We reviewed hematoxylin and eosin and CD1a, S100, and Langerin immunohistochemical–stained slides from 47 patients with well-documented demographic and clinical findings. Our cases included 8 children and 39 adults, with a mean follow-up of 63 months. All pediatric patients had concurrent multisystem LCH, presented with GI symptoms, and showed nonpolypoid lesions. Seven (88%) showed multifocal GI disease, including 5 with multiple GI organ involvement. All sampled lesions from children exhibited infiltrative growth. More than half had died of the disease or manifested persistent LCH at last follow-up. Twenty-five of 39 (64%) adults had LCH involving only the GI tract (single system), with the remaining 14 (36%) exhibiting multisystem disease. Adult single-system GI LCH was typically encountered incidentally on screening/surveillance endoscopy (72%). Most exhibited isolated colorectal involvement (88%) as a solitary polyp (92%), with a well-demarcated/noninfiltrative growth pattern (70%), and excellent prognosis (100%). In comparison, adult patients with multisystem LCH more frequently presented with GI symptoms (92%, P < .001), noncolorectal GI site involvement (50%, P = .02), multifocal GI lesions (43%, P = .005), nonpolypoid lesions (71%, P < .001), infiltrative histologic growth pattern (78%, P = .04), and persistent disease (57%, P < .001). Adult patients with multisystem LCH appear to exhibit similar clinicopathologic features to those of pediatric patients. These results demonstrated that adults with single-system LCH involving the GI tract have an excellent prognosis, whereas multisystem LCH occurring at any age carries an unfavorable prognosis. High-risk features of GI LCH include pediatric age, GI symptomatology, noncolorectal GI involvement, multifocal GI disease, nonpolypoid lesions, and infiltrative growth pattern.

122P Immune phenotypes and histological growth patterns in resected lung metastasis of colorectal cancer patients to assess prognosis

122P Immune phenotypes and histological growth patterns in resected lung metastasis of colorectal cancer patients to assess prognosis

Association of N-adhesin and focal adhesion kinase with frequency of tumor spread through the airspace (STAS) in stage I lung carcinoma and correlation with recurrence.

e20020 Background: Spread through air spaces (STAS) is one of the many modes of lung cancer dissemination. Aberrant activation of epithelial-mesenchymal transition (EMT) has been associated with enhanced tumor cell migration and invasiveness, a process that is accompanied by a decrease in adhesion molecules that maintain contact between epithelial cells, leading to cell separation and increased cell motility. Our objectives were to investigate the effect of adhesion molecule expression levels on STAS occurrence and postoperative recurrence in patients undergoing radical resection for stage I lung carcinoma. Methods: We examined the association of adhesion molecules with STAS as the primary endpoint and the Disease-Free Survival (DFS) as a secondary endpoint. E-cadherin, P-cadherin, N-cadherin, focal adhesion kinase (FAK), epithelial cell adhesion molecule (EpCAM) neural cell adhesion molecule 1 (NCAM1), vascular cell adhesion molecule 1 (VCAM1), intercellular cell adhesion molecule-1 (ICAM-1) were analyzed by immunohistochemistry in patients undergoing radical resection for stage I lung carcinoma. Associations between those adhesion molecules expression levels and STAS were determined by using the chi-square test and logistic regression model. DFS was analyzed by using the log-rank test and Cox proportional risk model. Results: As of January 1, 2024, 12 of 60 patients undergoing radical resection for stage I lung carcinoma had a disease recurrence. All of 60 patients’ tissue specimens were retrospectively analyzed, and there were no significant differences between patients with STAS-positive(n=30) and STAS-negative(n=30) in baseline clinicopathologic features, except for histological growth patterns, and lymphovascular invasion.Higher incidence of STAS was significantly associated with low expression of E-cadherin (P=0.002), high expression of N-cadherin (P=0.018) and FAK (P=0.027), and males (P=0.026), independent of tumor size, age, and clinical stage. Multivariate analysis showed that STAS (P=0.025), low E-cadherin/high N-cadherin (P=0.038), low E-cadherin/high FAK (P=0.025), and high N-cadherin/FAK (P=0.003) were significantly correlated with a higher risk of recurrence. In addition, females (P=0.034), and high N-cadherin/FAK (P=0.032) were associated with a high risk of recurrence in patients with STAS. Conclusions: Low expression of e-cadherin, high expression of N-cadherin and FAK were independent predictors of higher incidence of STAS. Tumors with low E-cadherin/high N-cadherin, low E-cadherin/high FAK, and high N-cadherin/FAK expression were important predictors of recurrence in patients with stage I lung carcinoma. Additionally, high N-cadherin/FAK expression in tumors provides information about a higher risk of recurrence in STAS-positive stage I lung carcinoma.

Comedo-like growth pattern in invasive early-stage cervical cancer: A new feature related to parametrial involvement

IntroductionThe standard surgical treatment for early-stage cervical cancer includes hysterectomy and bilateral oophorectomy along the removal of parametrial tissue to achieve surgical radicality. However, in recent years, the role of simple hysterectomy for cervical cancer with favorable prognostic characteristics has been re-evaluated. One of the challenges in early-stage cervical cancer is identifying predictive factors for neoplastic parametrial infiltration and lymph node metastases that cannot be detected during the preoperative assessment. We hypothesized that histological tumor growth patterns may be associated with these features and could thus be useful for the management of apparent early-stage cervical cancer. MethodWe identified 3 different histological patterns: the comedo-like, the infiltrative, and the expansive. We analyzed a series of clinic-pathological characteristics to determine the association of eachpatternwith aggressive features. Furthermore, we estimated odd ratios (ORs) in univariate and multivariate analyses for parametrial infiltration and lymph node metastasis. ResultsWe found that comedo-like pattern is associated to advanced FIGO stages, larger tumor size, lymphovascular space invasion, deeper invasion depth, parametrium involvement, and lymph node metastases. By univariate analysis, comedo-like pattern was statistically associated with both parametrial involvement (OR: 19.3, CI 5.47–68.6, p-value = < 0.001) and lymph node metastases (OR: 4.98, CI 1.71–14.5, p-value = 0.003). By multivariate analysis, the association between comedo-like pattern and parametrial involvement was confirmed (OR: 8.76, CI 2.34–32.75, p-value = 0.01). ConclusionThe specific growth pattern of cervical cancer, assessed in a conization specimen before hysterectomy, can be useful to tailor surgical radicality.

ASO Author Reflections: Histological Growth Patterns of Colorectal Peritoneal Metastases Significantly Affect Prognosis in Patients Presenting for Curative-Intent Cytoreductive Surgery.

ASO Author Reflections: Histological Growth Patterns of Colorectal Peritoneal Metastases Significantly Affect Prognosis in Patients Presenting for Curative-Intent Cytoreductive Surgery.

Retrospective Evaluation of the Prognostic Value of Histological Growth Pattern in Patients with Colorectal Peritoneal Metastases Undergoing Curative-Intent Cytoreductive Surgery.

Two distinct histological growth patterns (HGPs) were described in patients with peritoneal metastasis of colorectal cancer origin (PMCRC) with limited Peritoneal Cancer Index (PCI) ≤ 6 who did not receive neoadjuvant chemotherapy (NAC) and were treated with cytoreductive surgery (CRS) ± hyperthermic intraperitoneal chemotherapy (HIPEC): pushing HGP (P-HGP) and infiltrating HGP (I-HGP). Patients with dominant P-HGP (> 50%) had significantly better disease-free survival (DFS) and overall survival (OS). We aimed to determine whether these previous observations regarding the prognostic value of HGP in patients with PMCRC with low PCI (≤ 6) are also valid in all operable patients, regardless of whether they received NAC or not and regardless of PCI score. This was a retrospective study including 76 patients who underwent complete CRS ± HIPEC for PMCRC between July 2012 and March 2019. In each patient, up to five of the largest excised peritoneal nodules were analyzed for their tumor-to-peritoneum interface. Correlations between NAC, HGP, and prognosis were further explored. Thirty-seven patients (49%) had dominant P-HGP and 39 (51%) had dominant I-HGP. On univariate analysis, patients with P-HGP ≤ 50% had significantly lower OS than those with dominant P-HGP > 50% (39 versus 60 months; p = 0.014) confirmed on multivariate analysis (hazard ratio 2.4, 95% confidence interval 1.3-4.5; p = 0.006). There were no significant associations between NAC and type of HGP. This study confirms the prognostic value and reproducibility of the two previously reported HGPs in PMCRC. Dominant P-HGP is associated with better DFS and OS in patients undergoing curative-intent CRS ± HIPEC compared with I-HGP, independently of the extent of peritoneal disease burden.

Surgical Margins in Musculoskeletal Sarcoma.

» Negative margin resection of musculoskeletal sarcomas is associated with reduced risk of local recurrence.» There is limited evidence to support an absolute margin width of soft tissue or bone that correlates with reduced risk of local recurrence.» Factors intrinsic to the tumor, including histologic subtype, grade, growth pattern and neurovascular involvement impact margin status and local recurrence, and should be considered when evaluating a patient's individual risk after positive margins.» Appropriate use of adjuvant therapy, critical analysis of preoperative advanced cross-sectional imaging, and the involvement of a multidisciplinary team are essential to obtain negative margins when resecting sarcomas.

Evaluation of immunohistochemical expression of novel neuroendocrine marker INSM1 and histological tumor growth pattern in well-differentiated neuroendocrine tumors of the appendix: 15-year single tertiary center experience.

Well-differentiated neuroendocrine tumors of the appendix (A-WDNET) are the most common neoplasms of the appendix but are rare and incidental. INSM1 is a novel transcription factor marker with high sensitivity and specificity for neuroendocrine differentiation. It may display architecturally diverse tumor growth patterns including solid, nest, insular trabecular, and acinar. The aim of this study was to determine the staining expression of INSM1 in A-WDNETs and detail the morphological tumor growth patterns. INSM1 immunohistochemistry was performed on 35 A-WDNET patients. Tumors were histologically classified according to their growth patterns. Thirty-five patients, 60% of whom were male, had a mean age of 30 years at diagnosis and a mean tumor size of 0.9 cm. Eight percent of the tumors invaded the mucosa/submucosa, 34.3% showed invasion into the muscularis propria, 57.1% showed invasion into the subserosa or mesoappendix, LN metastasis was observed in two patients, lymph-vascular invasion in two patients, and perineural invasion in five patients. Ninety-four percent of the tumors were grade 1, the mitotic rate was >2% in two cases, and Ki-67 PI was >3% in two cases. INSM1 was positive in all cases (100%), 1+ 8.6%, 2+ 5.7%, 3+ 17.1%, 4+ 68.6%, weak staining in 11.4%, moderate staining in 22.9%, and strong staining in 67.7%. Type A histological growth pattern was observed in 54.3%, type B in 31.4%, and type C in 14.3% architecturally. INSM1 was positive in all A-WDNET morphological patterns and was 100% sensitive. INSM1 IHC can be used as an alternative to traditional neuroendocrine markers or in combination with the diagnosis of neuroendocrine tumors.

The association between KRAS and histopathological growth patterns and the impact on resection margins around vasculature and bile ducts in colorectal liver metastases.

The liver is the most frequent and often the only site of distant disease in colorectal cancer and, of all treatment protocols currently in use, resection is the most likely to result in long-term cure. Within the liver, tumour proximity to major vasculature and biliary structures poses a resection challenge, requiring a balance of achieving negative margins while preserving adequate vascular circulation and biliary drainage. The focus on parenchymal sparing resections are important but just as important may be the 'biological' behaviour of the tumour. In colorectal liver metastases (CRLM), biomarkers such as the Kirsten rat sarcoma oncogene homologue (KRAS) gene and histological growth patterns (HGPs) further improve the prognostication after resection. However, to date, the association between the KRAS status and HGPs in CRLM and their impact on resection margins around major vasculature or biliary structures in terms of overall survival and recurrence rates are unclear. The aim of this review was to explore the available evidence for the association between KRAS and HGPs in CRLM and attempt to define their impact on resection margins near major structures.

Osteosarcoma of the mandible and its management: A rare case report

Osteosarcoma is a classical malignant bone-forming neoplasm, characterised by osteoid synthesis by malignant osteoblasts. Osteosarcomas have an aggressive clinical course with a high mortality rate, despite their relatively low risk of distant metastases. The jaw bone is the most common site of occurrence in the head and neck region. These neoplasms often show characteristic clinical behaviours, varied radiological appearances, and a wide-ranging histological growth pattern. Early diagnosis and radical surgery, followed by radiotherapy and chemotherapy if required, have been the treatment of choice. This case report emphasises the importance of early diagnosis of this tumour based on clinical features, radiographic examination, and confirmation by histopathology. Confirmation of the final diagnosis of osteosarcoma often requires a histopathological examination of the multiple biopsy specimens. Adjuvant chemotherapy followed by radical surgery resulted in an excellent prognosis in the present case. Considering the rarity of the neoplasm, its fast progression, and its aggressiveness, the present case report would contribute to a better understanding of osteosarcomas involving the jaw bone and the management of the tumour involving the central arch of the mandible with involvement of the adjacent soft tissue structures.

Role of stromal PD-L1 expression in colorectal liver metastasis

Background and AimThe outcomes of immune checkpoint blockade for colorectal cancer (CRC) treatment are unsatisfactory. Furthermore, the efficacy of immune checkpoint blockade for liver metastasis of various cancer is poor. Here, we investigated the relationship between stromal programmed death-ligand 1 (PD-L1) expression and the prognosis of patients with colorectal cancer liver metastasis (CRLM).MethodsThe present study enrolled 84 CRLM patients who underwent surgery (R0) for CRC. Immunohistochemistry was performed to analyze stromal PD-L1 expression in CRLM.ResultsStromal PD-L1 was expressed in 52.3% of CRLM samples, which was associated with fewer not optimally resectable metastases (p = 0.04). Stromal PD-L1 also tended to associate with a lower tumor grade (p = 0.08). Stromal PD-L1-positive patients had longer overall survival (p = 0.003). Multivariate analysis identified stromal PD-L1 expression (p = 0.008) and poorer differentiation (p < 0.001) as independent prognostic indicators. Furthermore, stromal PD-L1 expression was correlated to a high number of tumor-infiltrating lymphocytes (TILs). Stromal PD-L1– and low TIL groups had shorter OS than stromal PD-L1 + and high TIL groups (46.6% vs. 81.8%, p = 0.05) Stromal PD-L1-positive patients had longer disease-free survival (DFS) (p = 0.03) and time to surgical failure (p = 0.001). Interestingly, stromal PD-L1 expression was positively related to the desmoplastic subtype (p = 0.0002) and inversely related to the replacement subtype of the histological growth pattern (p = 0.008).ConclusionsStromal PD-L1 expression may be a significant prognostic marker for CRLM.

Proteomic analysis reveals LRPAP1 as a key player in the micropapillary pattern metastasis of lung adenocarcinoma

ObjectivesLung adenocarcinomas have different prognoses depending on their histological growth patterns. Micropapillary growth within lung adenocarcinoma, particularly metastasis, is related to dismal prognostic outcome. Metastasis accounts for a major factor leading to mortality among lung cancer patients. Understanding the mechanisms underlying early stage metastasis can help develop novel treatments for improving patient survival. MethodsHere, quantitative mass spectrometry was conducted for comparing protein expression profiles among various histological subtypes, including adenocarcinoma in situ, minimally invasive adenocarcinoma, and invasive adenocarcinoma (including acinar and micropapillary [MIP] types). To determine the mechanism of MIP-associated metastasis, we identified a protein that was highly expressed in MIP. The expression of the selected highly expressed MIP protein was verified via immunohistochemical (IHC) analysis and its function was validated by an in vitro migration assay. ResultsProteomic data revealed that low-density lipoprotein receptor-related protein–associated protein 1 (LRPAP1) was highly expressed in MIP group, which was confirmed by IHC. The co-expressed proteins in this study, PSMD1 and HSP90AB1, have been reported to be highly expressed in different cancers and play an essential role in metastasis. We observed that LRPAP1 promoted lung cancer progression, including metastasis, invasion and proliferation in vitro and in vivo. ConclusionLRPAP1 is necessary for MIP-associated metastasis and is the candidate novel anti-metastasis therapeutic target.

Unraveling the Transcriptional Landscape of Nodular Lymphocyte-Predominant Hodgkin Lymphoma and T-Cell/Histiocyte Rich Large B-Cell Lymphoma: Impact of Tumor Microenvironment and Checkpoint Gene Expression

Introduction: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare B-cell malignancy with a paucity of malignant cells embedded in a diverse tumor microenvironment (TME). The histological composition of the TME is known to influence outcomes, with nodular B-cell rich TME (classical histology, Fan patterns A&amp;B) associated with indolent clinical course, while T-cell infiltration or diffuse growth (variant histology, Fan patterns C-F) may resemble aggressive T/cell-histiocyte rich large B-cell lymphoma (THRLBCL) to which NLPHL can transform. Molecular features of NLPHL and THRLBCL remain to be discovered. To gain further insights into the biology of these lymphomas, we recruited NLPHL and THRLBCL cases as part of the Atlas of Blood Cancer Genomes (ABCG) initiative, a consortium consisting of 26 institutions. Design: We collected comprehensive clinicopathological, treatment and outcome data from 154 NLPHL and 21 THRLBCL patients, with centralized pathology review performed by a panel of dedicated hematopathologists. Fan patterns of the NLPHL samples were documented in all samples where possible. RNA sequencing was performed on formalin-fixed paraffin-embedded (FFPE) diagnostic tumor samples (n=129 NLPHL; n=17 THRLBCL). Tumor-infiltrating immune cell compositions were enumerated using FARDEEP with signature matrix LM22 from CIBERSORT. Results: Median age at diagnosis for the patients with THRLBCL and NLPHL was 54 years (interquartile ratio [IQR] 43-65) and 40 years (IQR 24-53), respectively. The majority of patients with NLPHL had limited stage (74%), whereas the patients with THRLBCL predominantly had advanced stage at diagnosis (95%). In both diseases, most patients were males (NLPHL, 69%; THRLBCL, 76%). Spleen involvement was present in 11 NLPHL patients (8%) and histological growth pattern was documented in 112 patients (73%). Out of those, 47 (42%) presented with variant histology and 65 with classical histology. Variant histology was enriched in NLPHL patients with splenic involvement. During a median follow-up of 6.4 years (IQR 3.8-10.1), 12 NLPHL patients and 9 THRLBCL patients died. Patients with THRLBCL had worse 10-year overall survival (OS, 31% vs 89%; p&amp;lt;0.001) and progression-free survival (PFS, 30% vs 66%; p=0.002) compared to patients with NLPHL. Moreover, NLPHLs with variant histology had inferior 10-year OS compared to NLPHLs with classical histology (81% vs 91%; P=0.03; Figure 1). According to in silico immunophenotyping, THRLBCL cases had the highest median proportions of M1-macrophages (11.0%) and CD8+ T-cells (17.0%), followed by NLPHLs with variant histology (M1-macrophages, 6.5%; CD8+ T-cells, 14.5%), with the lowest proportion observed in NLPHLs with classical histology (M1-macrophages, 5.2%; CD8+ T-cells, 10.9%). In contrast, the median proportions of naïve B cells followed an opposite trend across subtypes (NLPHL classical histology, 15.5%; NLPHL variant histology, 11.0%; THRLBCL, 2.0%), whereas the median proportion of CD4+ T-cells was similar across both lymphomas (NLPHL classical histology, 33.9%; NLPHL variant histology, 33.9%; THRLBCL, 32.4%). Despite differences in the overall transcriptomic landscape, gene expression patterns posited THRLBCL and NLPHL as comprising a biological continuum. THRLBCL shared more similarities with NLPHL with variant histology, while NLPHLs with classical histology exhibited upregulation of genes related to cell growth and proliferation through the MYC pathway (P&amp;lt;0.001). Finally, we identified a strong association between THRLBCL and upregulation of checkpoint genes (P&amp;lt;0.001) and gene expression related to inflammatory response (P&amp;lt;0.001) (Figure 2). Furthermore, NLPHLs with a high checkpoint score (above the 75th percentile) were associated with spleen involvement (P&amp;lt;0.001) and worse outcome (5-year PFS 61% vs 87%; P=0.02). Conclusion: Our study provides the largest comprehensive clinical and transcriptomic analyses of NLPHL and THRLBCL to-date. The findings suggest that the inferior outcomes observed in THRLBCL and in a subset of NLPHL are attributable to a higher degree of inflammation in the TME, increased expression of checkpoint genes, and a high proportion of macrophages.

T1a Renal Cell Carcinoma With Metastasis: Japanese Society of Renal Cancer Retrospective Multi-institute Results.

Small renal cell carcinomas (sRCC) have drastically increased in recent years. Considering that sRCC have heterogeneous biology, it would be clinically relevant if specific clinical or pathological parameters could predict sRCC metastasis. In the present study, we aimed to assess the clinicopathological factors of pathologic T1a RCC (pT1a RCC) with or without metastasis to explore factors predicting metastasis. The present study included 198 patients with pT1a RCC who underwent radical or partial nephrectomy at fifteen institutions belonging to the Japanese Society of Renal Cancer, between1985 and 2017. Clinicopathological parameters, including age, sex, tumour size, tumour side, histological subtype, histological nuclear grade, lymphovascular invasion, and histological growth patterns, were analysed. Fuhrman grade 3 or 4 tumours and infiltrative tumour growth patterns were significantly higher in patients with metastasis than in those without. The most common site of synchronous metastasis was the bone in patients with pT1a RCC (65.4%), whereas for patients with post-surgery metachronous metastasis (46.2%), it was the lungs. Histological growth pattern and nuclear grade are vital for predicting metastasis in pT1a RCC, suggesting careful long-term follow-up for such patients.

Infiltrative solid papillary carcinoma of the breast with axillary lymph node metastasis: a case report

BackgroundSolid papillary carcinoma (SPC) is a rare breast papillary tumor variant. The main histological features of SPC consist of neoplastic cell-rich nodules with thin fibrovascular cores, often accompanied by mucous secretion and neuroendocrine differentiation. Infiltrative solid papillary carcinoma (ISPC) tumor cells have an invasive, map-like growth pattern with serrated irregular growth. Due to its unique clinicopathological features, SPC is classified as two pathological tissue types based on the 2019 WHO classification of breast tumors: SPC in situ and ISPC.Case presentationWe report a case of a 55-year-old female patient who was admitted to the hospital due to a painless left breast mass that had persisted for two years. Mammography suggested a mass in the left upper outer quadrant (BI-RADS 4B), and ultrasound of the breast demonstrated a cystic mass of the left breast (US_BI_RADS 4 C) with multiple enlarged lymph nodes in the left axilla. Postoperative pathology revealed ISPC with one lymph node metastasis in the left breast. Modified radical mastectomy was performed on the left breast. Subsequently, the patient received letrozole endocrine therapy, epirubicin hydrochloride and cyclophosphamide chemotherapy, and radiotherapy of the left chest wall and left upper and lower clavicular regions. After 17 months of follow-up, there was no evidence of recurrence or distant metastasis.ConclusionsSPC is a group of heterogeneous tumors. SPC in situ has a good prognosis. In contrast, ISPC has a unique histological morphology and growth pattern with invasive biological behavior that can lead to lymph node and distant metastases.

Histologic pattern analysis of cutaneous basal cell carcinoma at a tertiary care hospital in South India

Basal cell carcinoma (BCC) is one of the common malignant disease of the skin worldwide. An attempt at a simplified, accurate histologic classification of BCC based on histologic growth patterns is done in this study. This paved way to the concept of risk typing BCC into low and high-risk types. This is a retrospective descriptive study of skin biopsies diagnosed as BCC between 2010 and 2018 in the Department of Pathology in a tertiary care teaching hospital in Karnataka. H&amp;E stained sections were reviewed, histopathologically subtyped and further categorized into high and low risk types. IHC for BerEP4 was done in ten diagnostically challenging cases. The patients were followed up for six months after the study period. 79 cases of BCC were studied with majority of them being classified as high risk BCC (83.54%), with nodular type (51.89%) being the most common histological subtype. BCCs were seen predominantly in patients in the sixth decade with a female preponderance in both high and low risk BCCs. Majority of the patients with genetic predispositions were of young age and included xeroderma pigmentosa and oculocutaneous albinism. IHC for BerEP4 showed strong and diffuse membranous staining in all ten cases. Recurrence was noted in two cases and metastasis following three recurrences was noted in one case. An accurate histologic classification of BCC based on growth pattern is of great significance as it reflects the biological behaviour of the tumour. Risk typing BCC into high and low risk types further guides the management of BCC. High risk categories mandate more aggressive and decisive treatment to prevent recurrences and also helps predict the prognosis for the patient.

Circulating extracellular vesicles containing S100A9 reflect histopathology, immunophenotype and therapeutic responses of liver metastasis in colorectal cancer patients

BackgroundMetastasis is the principal cause of cancer treatment failure and an area of dire diagnostic needs. Colorectal cancer metastases to the liver (CRCLMs) are predominantly classified into desmoplastic and replacement based on their histological growth patterns (HGPs). Desmoplastic responds well to current treatments, while replacement HGP has a poor prognosis with low overall survival rates.MethodsWe hypothesised that complex cellular response underlying HGPs may be reflected in the proteome of circulating extracellular vesicles (EVs). EV proteomics data was generated through LC-MS/MS and analysed with Maxquant and Perseus. To validate the S100A9 signature, ELISA was performed, and IHC and IF were conducted on tissue for marker detection and colocalization study.ResultsPlasma EV proteome signature distinguished desmoplastic from the replacement in patients with 22 differentially expressed proteins, including immune related markers. Unsupervised PCA analysis revealed clear separation of the two lesions. The marker with the highest confidence level to stratify the two HGPs was S100A9, which was traced in CRCLM lesions and found to colocalize with macrophages and neutrophils. EV-associated S100A9 in plasma may reflect the innate immunity status of metastatic lesions and their differential therapeutic responses.ConclusionPlasma EV-derived S100A9 could be useful in personalising therapy in patients with CRCLM.