C-C Chemokine 21-Expressing T-cell Zone Fibroblastic Reticular Cells, Abundant in Lymph Nodes, Are Absent in Cancer Lymphoid Stroma.

Cancer tissue generally possesses an immunosuppressive microenvironment. However, some cancers are associated with lymphoid stroma (i.e., a widely developed tertiary lymphoid structure). The T-cell zone (paracortex) of secondary lymphoid organs, particularly lymph nodes, is characterized by an abundance of T-cell zone fibroblastic reticular cells (TCZ-FRCs) that express C-C motif chemokine ligand 21 (CCL21) and smooth muscle actin (SMA). We analyzed the presence of TCZ-FRCs in 30 cases of carcinomas with lymphoid stroma of the breast, stomach, colon, tongue, and skin. Immunohistochemistry corroborated the abundance of CCL21+ SMA+ TCZ-FRCs in the normal lymph nodes. In sharp contrast, all 30 carcinomas with lymphoid stroma displayed no CCL21+ SMA+ TCZ-FRCs despite the affluence of T cells. Real-time reverse transcription polymerase chain reaction confirmed a marked decrease in the messenger ribonucleic acid expression of CCL21 and its receptor C-C motif chemokine receptor 7 in cancer lymphoid stroma compared to that in lymph nodes. Next, we analyzed the T cell phenotypes. The cancer lymphoid stroma demonstrated an abundance of CD3+ CD62L- memory-type T cells, in contrast to the presence of CD3+ CD62L+ naïve- and central memory T cells in the T cell zone of lymphoid tissues. Our data demonstrated the following: 1) Cancer lymphoid stroma lacked TCZ-FRCs with abundance of more activated T cells than in lymph nodes and 2) these were common phenomena in cancer lymphoid stroma irrespective of the histological types and organs involved.

Prognosis of EBV-positive gastric cancer with lymphoid stroma: systematic review and meta-analysis.

BACKGROUND: Although gastric cancer with lymphoid stroma (GCLS) presents better prognosis, uncertainty still exists regarding the association of Epstein-Barr virus (EBV) infection with prognosis of GCLS. Therefore, it is urgent to evaluate the outcome and characteristics of EBV-positive GCLS via a systematic review and meta-analysis. METHODS: Three medical databases, with a period ranging from 2000 to so far, were searched for observational studies on EBV infection, clinical characteristics and prognosis. Odds ratio (OR) was used to evaluate the mortality and clinical characteristics of EBV-positive GCLS patients. Egger's test and subgroup analysis were conducted to identify the source of heterogeneity. RESULTS: Nine retrospective studies were finally identified, which involved 618 EBV-positive and 153 EBV-negative GCLS patients. The forest plot indicated that EBV-positive GCLS patients had lower mortality (p = .009; 95% CI: 0.15-0.77; I2 = 48.6%). Both of funnel plot and Egger's tests suggested that there was no publication bias. Nonetheless, subgroup analysis indicated that T1-2 stage ratio more than 50% (p < .001; I2 = 6.7%) and male ratio more than 80% (p < .001; I2 = 0.0%) were valuable for eliminating the heterogeneity. Seven studies including valid information showed that TNM stage of EBV-positive and negative GCLS patients was not statistically different (p = .644; 95% CI: 0.50-1.53; I2 = 0.0%). CONCLUSIONS: EBV-positive GCLS tends to have lower mortality, suggesting that detection of EBV infection is necessary to predict prognosis of GCLS.

A Rare Case of Primary Adenocarcinoma of the Gallbladder With Lymphoid Stroma.

Adenocarcinoma of the gallbladder is the most common gallbladder carcinoma. But lymphoid stroma in gallbladder carcinoma is one of the rarest presentations. A unique case of gallbladder adenocarcinoma with lymphoid stroma in a 47-year-old female is presented in this report. The surgically resected gallbladder demonstrated invasive adenocarcinoma with lymphoid stroma, though it was radiologically diagnosed as xanthogranulomatous cholecystitis. Adenocarcinoma was immunohistochemically positive for pancytokeratin (AE1/AE3), cytokeratin 7 (CK7), cytokeratin 20 (CK20), and carcinoembryonic antigen (CEA). Lymphoid stroma was positive for CD45, where B-cell zones were CD20 and CD79a positive, and T-cell zones were CD3 positive, with a larger T-cell subset being positive for CD4 than CD8. This is the fourth reported case of gallbladder adenocarcinoma with lymphoid stroma, which needs to be studied for pathogenesis, prognosis, and future therapy, if any.

Endoscopic Diagnosis and Therapy for Epstein-Barr Virus-Associated Gastric Cancer.

Epstein-Barr-virus-associated gastric cancer (EBVaGC) represents almost 7% of all GC and is a distinct subtype of GC with extreme DNA hypermethylation. EBVaGC is a tumor-infiltrating lymphocyte-rich tumor with little lymph-node metastasis in its early stage and with a relatively favorable prognosis in its advanced stage. Using upper gastrointestinal endoscopy, we recognize EBVaGC as a mainly depressed type with SMT-like protrusion in the upper part of the stomach near the gastric mucosal atrophic border or remnant stomach. The EBVaGC recognition rate of 21.4% with the endoscopic motif is not high, and further progress in endoscopic diagnosis of EBVaGC is needed. As less invasive endoscopic therapy, the extension of the criteria of endoscopic submucosal dissection (ESD) for early EBVaGC with little lymph-node metastasis should be discussed. Endoscopic diagnosis of EBVaGC may be relevant for the selection of patients who could benefit from endoscopic treatment or chemotherapy.

P16 expression and presence of lymphoid stroma are correlated with good prognosis in mucoepidermoid carcinoma of the head and neck.

BACKGROUND: Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy. This study was designed to identify valuable prognosticator in MEC. METHODS: Histopathologic analysis, immunohistochemistry, and in situ hybridization were performed on 128 carcinomas diagnosed as MEC of the head and neck. RESULTS: Expression of p16 was found in 96 cases (76%) of MEC. Lymphoid stroma was identified in 63 cases (49%). There was a significant correlation between loss of p16 expression and absence of lymphoid stroma. Expression of p16 was significantly associated with better clinicopathologic features. Lymphoid stroma was significantly associated with lower histologic grade. Overall survival (OS) was significantly longer in cases expressing p16 (P = 0.00096) and lymphoid stroma cases (P = 0.0023). Multivariate analysis revealed loss of p16 expression as negative prognosticators for OS. CONCLUSION: Our data showed p16 expression and the presence of lymphoid stroma were significantly associated with good clinical outcomes. Testing for these factors could lead to better prognostication and treatment of patients with MEC.

Gastric cancer with distinct Epstein-Barr virus-positive and -negative tumor components and their whole exome sequencing result: a case Report.

BACKGROUND: Epstein-Barr virus (EBV)-associated gastric cancer exhibits distinct clinicopathologic characteristics, showing a good response to immune checkpoint inhibitors and a favorable prognosis. However, gastric cancer comprising distinct EBV-positive and -negative components in a single mass have been rarely reported, and their detailed genetic characteristics have not yet been investigated. Therefore, we reported the case of gastric cancer exhibiting distinct EBV-positive and -negative areas and further investigated its genetic characteristics. CASE PRESENTATIONS: A 70-year-old man underwent distal gastrectomy for gastric cancer, which was detected during a routine health check-up. EBV-encoded RNA in situ hybridization revealed distinct EBV-positive and -negative components at each other's borders, morphologically consistent with collision tumor. We separately sequenced EBV-positive and -negative tumor areas through whole exome sequencing (WES) with matched normal tissue. Remarkably, both EBV-positive and -negative areas shared pathogenic mutations of ARID1A, KCNJ2, and RRAS2. Furthermore, they shared 92 somatic single nucleotide variants and small insertion or deletion mutations, of which 32.7% and 24.5% are EBV-positive and -negative tumor components, respectively. CONCLUSIONS: WES results suggested that gastric cancer with distinct EBV-positive and -negative tumor components, formerly categorized as a collision tumor, can be clonally related. EBV-negative tumor component might be associated with loss of EBV during tumor progression.

Constant p.L424H Mutation in GTF2I in Micronodular Thymomas With Lymphoid Stroma: Evidence Supporting Close Relationship With Type A and AB Thymomas.

Micronodular thymoma with lymphoid stroma is a rare thymic neoplasm characterized by discrete nodules of epithelial tumor cells separated by abundant lymphoid stroma. The genetic features of micronodular thymoma with lymphoid stroma remain largely unexplored. Owing to the interference of abundant intratumoral, nonneoplastic lymphoid cells, a highly sensitive approach is necessary to study genetic changes in these tumors. In this study, we used a highly sensitive next-generation sequencing assay using the molecular barcoding Ion AmpliSeq HD technology to study the most commonly mutated genes in thymomas, including GTF2I, HRAS, NRAS, KRAS, and TP53. A total of 12 cases of micronodular thymomas with lymphoid stroma were tested, and 2 cases also had areas of type A thymoma in their tumor bed. Two micronodular thymic carcinomas with lymphoid stroma, a histological mimic of micronodular thymoma, were also included for comparison. Recurrent p.L424H mutations in GTF2I were found in all the cases of micronodular thymoma with lymphoid stroma but not in the cases of micronodular thymic carcinomas. In addition, 3 cases of micronodular thymoma with lymphoid stroma also had concomitant HRAS and/or KRAS mutations. Our study showed that p.L424H mutations in GTF2I is a constant genetic feature of micronodular thymoma with lymphoid stroma. This finding strongly suggests that micronodular thymoma with lymphoid stroma is closely related to type A and AB thymomas because they all share p.L424H mutations in GTF2I.

Case report: Gastric adenosquamous carcinoma with EBV-positive component of squamous cell carcinoma mixed with gastric carcinoma with lymphoid stroma: A novel case report and literature review.

Background: Gastric adenosquamous carcinoma with EBV-positive component of squamous cell carcinoma mixed with gastric carcinoma with lymphoid stroma are extremely unusual variants of gastric carcinoma. We herein reported such a case and summarized five related cases that have been reported previously. Case presentation: A 59-year-old man was admitted to our hospital with upper abdominal discomfort and acid reflux. Gastric endoscopic examination revealed an irregular ulcer in the gastric angle. Biopsy of the lesion revealed adenocarcinoma. The patient underwent laparoscopic distal gastrectomy with lymph node dissection subsequently. Histologically, the tumor showed coexistence of GASC and GCLS. SCC and GCLS were positive for EBER in situ hybridization, while adenocarcinoma component was negative. Accordingly, the present case was diagnosed as GASC with EBV-positive component of SCC mixed with GCLS. Conclusion: GASC with EBV-positive component of SCC mixed with GCLS is extremely rare. Although the pathogenesis of GASC and the role of EBV in the development of an ASC component have not been fully elucidated, this case will help clinicians and pathologists better understand this special subtype of gastric tumor.

Clinical Significance of Epstein-Barr Virus and Helicobacter pylori Infection in Gastric Carcinoma.

Background/Aims: Epstein-Barr virus (EBV) and Helicobacter pylori (HP) coinfection may synergistically induce severe inflammatory responses in the stomach tissue, increasing the risk of developing gastric cancer. We aimed to analyze the effect of EBV and HP coinfection on the clinicopathologic features and prognosis of gastric cancer, as well as to evaluate the role of EBV infection in non-gastric carcinoma with lymphoid stroma (non-GCLS). Methods: Overall, 956 patients who underwent surgery for gastric cancer between September 2014 and August 2015 were eligible and divided into groups, according to GCLS morphology, EBV infection, and HP infection. Clinicopathologic characteristics and oncologic outcomes were analyzed retrospectively. Results: EBV and HP coinfection was significantly associated with male sex, proximal location, GCLS morphology, and equivocal p53 expression (p<0.001). Multivariate analysis revealed that EBV infection alone (hazard ratio [HR], 0.362; 95% CI, 0.131 to 0.996; p=0.049) and lower third location (HR, 0.624; 95% CI, 0.413 to 0.943; p=0.025) were inversely correlated with overall survival. During median follow-up period of 72 months, overall survival rate was not significantly different between the EBV and HP coinfection group and others (97.6% vs 86.8%; log-rank p=0.144). In non-GCLS patients (n=920), overall survival rate was not significantly different between the EBV infection group and others (96.9% vs 86.4%; log-rank p=0.126). Conclusions: EBV and HP coinfection is not an independent prognostic factor for gastric cancer. EBV infection status, regardless of HP infection, affects the clinicopathologic features of all types of gastric cancer. However, it does not lead to a significant difference in overall survival of non-GCLS patients.

Two Thymomas of Different Histological Subtypes Arising in a Giant Thymolipoma: Case Report and Review of the Literature.

Thymolipoma is a rare benign tumor of the anterior mediastinum. Only a few reports describing thymoma arising within a thymolipoma have been documented in the literature. We report herein a detailed description of thymolipoma giving rise to 2 thymomas of different histological subtypes. A 74-year-old male with history of metastatic papillary thyroid carcinoma gradually developed 2 soft tissue nodules within a large right hemithorax fatty mass that was present for the past 20 years. Computed tomography (CT)-guided needle biopsy revealed one of the soft tissue nodules to be a thymoma, and the entire mass was surgically resected. Final pathological examination demonstrated the mass to be a thymolipoma containing a micronodular thymoma with lymphoid stroma as well as a WHO type B1 thymoma. No evidence of disease recurrence was seen at the time of his 7-year follow-up. This case documents a rare presentation of thymolipoma harboring 2 thymomas of different histological subtypes and highlights the need for early surgical resection of thymolipomas, as they may harbor malignant nodules.

Experimental model of micronodular thymic neoplasm with lymphoid stroma.

BACKGROUND: Micronodular thymic neoplasm with lymphoid stroma (MNT), a subtype of thymic tumor, is histopathologically characterized by micronodular thymic epithelial cell nests with lymphoid stroma. Despite the distinct histopathology of MNT, its pathogenesis remains unclear. METHODS: In this study, we aimed to examine a thymic tumor harboring thymic epithelial and lymphoid cells in a nonobese diabetic/severe combined immunodeficiency mouse. RESULTS: The excised tumor cells were cultured in vitro and comprised epithelial tumor cells and lymphoid cells. During a three-dimensional cell culture, the epithelial tumor cells formed micronodular cell nests surrounded by lymphoid stroma. Notably, the lymphoid cells underwent apoptosis when they were separated from the epithelial tumor cells. Cutaneous transplantation of the cultured epithelial cells with splenocytes from BALB/c mice led to tumor formation, and these cells demonstrated a histopathology similar to that of human MNT in a nonobese diabetic/severe combined immunodeficiency mouse. CONCLUSION: Given its overlapping features with human MNT, the transplanted tumor could serve as an experimental model of this disease.

EBV persistence in gastric cancer cases conventionally classified as EBER-ISH negative.

BACKGROUND: The Epstein-Barr virus (EBV) causes various B-cell lymphomas and epithelial malignancies, including gastric cancer (GC) at frequencies ranging from 5 to 10% in adenocarcinomas (ADK) to 80% in GC with lymphoid stroma (GCLS). Using high-sensitivity methods, we recently detected EBV traces in a large cohort of EBV-negative B-cell lymphomas, suggesting a hit-and-run mechanism. METHODS: Here, we used routine and higher-sensitivity methods [droplet digital PCR (ddPCR) for EBV segments on microdissected tumour cells and RNAscope for EBNA1 mRNA] to assess EBV infection in a cohort of 40 GCs (28 ADK and 12 GCLS). RESULTS: ddPCR documented the presence of EBV nucleic acids in rare tumour cells of several cases conventionally classified as EBV-negative (ADK, 8/26; GCLS, 6/7). Similarly, RNAscope confirmed EBNA1 expression in rare tumour cells (ADK, 4/26; GCLS, 3/7). Finally, since EBV induces epigenetic changes that are heritable and retained after complete loss of the virus from the host cell, we studied the methylation pattern of EBV-specifically methylated genes (Timp2, Eya1) as a mark of previous EBV infection. Cases with EBV traces showed a considerable level of methylation in Timp2 and Eya1 genes that was similar to that observed in EBER-ISH positive cases and greater than cases not featuring any EBV traces. CONCLUSIONS: These findings suggest that: (a) EBV may contribute to gastric pathogenesis more widely than currently acknowledged and (b) indicate the methylation changes as a mechanistic framework for how EBV can act in a hit-and-run manner. Finally, we found that the viral state was of prognostic significance in univariate and multivariate analyses.

Clinicopathological Characteristics of Advanced Epstein-Barr Virus-associated Gastric Cancer Highlighting Aberrant p53 Expression.

BACKGROUND/AIM: Epstein-Barr virus (EBV)-associated gastric cancer is a distinct subtype of stomach adenocarcinoma. Although previous studies have investigated its clinicopathological characteristics, there is a lack of research focusing on advanced EBV-associated gastric cancer. In this study, we performed a comprehensive review of advanced EBV-associated gastric cancer cases. PATIENTS AND METHODS: We retrospectively collected 18 consecutive cases of surgically resected advanced EBV-associated gastric cancer. Clinicopathological parameters were investigated using histological review, immunohistochemistry, and a review of the electronic medical records of the hospital. RESULTS: The predominant histological pattern of advanced EBV-associated gastric cancer, according to the Laurén classification, was intestinal-type adenocarcinoma with varying degrees of differentiation. However, focal areas showing conventional gastric carcinoma with a lymphoid stromal pattern were found in all cases except one. In addition to the previously described histological patterns of EBV-associated gastric cancer, one case displayed chronic granulomatous inflammation-like histology with barely identifiable malignant epithelial cells. Another case had a pure signet-ring cell carcinoma component showing nuclear positivity for the EBV-encoded RNA in situ hybridization assay. Remarkably, five out of 18 cases (27.8%) showed aberrant p53 expression on immunostaining, which is known to occur rarely in EBV-associated gastric cancer. All cases with aberrant p53 expression had intestinal-type adenocarcinoma-like components. CONCLUSION: Advanced EBV-associated gastric cancer had distinct histology and a higher rate of aberrant p53 immunostaining pattern than conventional EBV-associated gastric cancer. Therefore, their biological behavior should be investigated separately.

Treatment of gastric carcinoma with lymphoid stroma by immunotherapy: A case report.

BACKGROUND: Gastric cancer with lymphoid stroma (GCLS) is a rare type of gastric cancer characterized by abundant lymphocytic infiltration of the stroma. It is an Epstein-Barr virus-associated gastric cancer with a better prognosis than typical gastric cancer but with similar symptoms. GCLS diagnosis is based on pathological, histological and immunohistochemical examination and there are no standardized guidelines for treatment. CASE SUMMARY: This case report describes a 72-year-old man with a 6-mo history of abdominal pain. Endoscopy revealed ulcerative lesions in the stomach and gastric cancer was suspected. A preoperative endoscopic biopsy indicated undifferentiated carcinoma and postoperative pathological, histological and immunohistochemical analyses of the resected specimen confirmed a final diagnosis of GCLS. CONCLUSION: The patient showed high programmed cell death-ligand 1 expression and recovered well after immunotherapy.

Epstein-Barr virus-associated gastric adenosquamous carcinoma with concurrent gastric carcinoma with lymphoid stroma: a case report and review of the literature.

BACKGROUND: Adenosquamous carcinoma (ASC)with concurrent gastric carcinoma with lymphoid stroma (GCLS) are extremely rare tumors. There are only limited cases reported in the literature. Epstein-Barr virus (EBV) infection was found in the concomitant GCLS, but none in the ASC. Here, we report the first case of gastric cancer with EBV infection detected in both ASC and GCLS. CASE PRESENTATION: A 59-year-old man complained of intermittent upper abdominal pain. The gastric endoscopy revealed a type IIc tumor located in the gastric body near the fundus of the stomach. Histological examination of the gastric tumor showed the coexistence of ASC and GCLS. Both components were positive for EBV-encoded RNA (EBER) in situ hybridization. Neoplastic nests of the former were positive for p63, p40 and CK5/6. The glandular components showed positive acid mucus in the Alcian-blue periodic-acid-schiff (AB-PAS) staining. There was significant difference in the expression of epidermal growth factor receptor (EGFR) between adenocarcinoma and squamous carcinoma, but not in other proteins such as human epidermal growth factor receptor 2 (HER2), p53 and mismatch repair proteins. The role of EGFR signaling pathway needs to be further explored in the differentiation of squamous carcinoma in the gastric ASC. Finally, a diagnosis of early EBV associated gastric ASC with concurrent GCLS (pT1bN1) was made. The patient took a single-drug S1 periodically for half a year after the surgery and has been disease free during 8 months of medical follow-up. CONCLUSIONS: This is the first case of EBV associated gastric ASC with concurrent GCLS, and pathologists and clinicians should recognize and pay attention to this type of tumor.

Gastric carcinoma with lymphoid stroma derived from hamartomatous inverted polyp with osteoclast-like giant cells: a case report.

Gastric carcinomas with lymphoid stroma (GCLS) are characterized by prominent stromal infiltration of lymphocyte and account for 1-4% of gastric cancers. Although, osteoclast-like giant cells (OGC) have been reported in some GCLS, OGCs in gastric tumors is exceedingly rare. A 60-year-old woman presented to our hospital after the finding of a positive fecal blood test during a routine medical check. Esophagogastroduodenoscopy revealed a Type 0-III + IIc tumor in the middle part of the gastric body. Biopsy revealed a poorly differentiated tumor and she was referred to our department. Early phase computed tomography showed thickening of the wall in the middle of the gastric body and enlargement of nearby lymph nodes. Laparoscopic total gastrectomy was performed. Pathological examination revealed a hamartomatous inverted polyp (HIP) in the submucosal layer with tub2-por1 tumor in the HIP. Prominent lymphocytic infiltration and OGCs were found around the tumor. Immunohistochemical analysis showed that the tumor cells were negative for EBER, MLH-1, and MSH2, 6. These findings suggest that this tumor was a non-microsatellite instability (MSI)-high GCLS without Epstein-Barr virus (EBV) infection. The patient's postoperative course was uneventful and she was discharged 11 days after surgery. She remains well 3 years after surgery.

Gastric Carcinoma with Lymphoid Stroma: A Combination of Mismatch Repair Deficient Medullary Type and Epstein-Barr Virus-associated Gastric Carcinomas.

Gastric carcinomas consist of a heterogeneous group of neoplasms with broad cytological and architectural variations. Gastric carcinomas with lymphoid stroma show poor correlation between their histomorphology and biological behavior. This contrast causes a need for more detailed analysis and molecular exploration of lymphoid stroma-rich gastric carcinomas with medullary like features and lack of glandular differentiation. In this study, we performed a detailed retrospective analysis of 53 gastric carcinomas among 654 gastric tumors from surgical resection specimens, all of which had no prominent glandular differentiation. Morphological and clinical data were compared with immunohistochemistry (MLH1, PMS2, MSH2 and MSH6 for mismatch repair mechanism deficiency; CD2, CD8 and CD163 for immune infiltration; and PD-1, PD-L1, LMP-1, ERBB2 and ki-67) besides EBER in situ hybridization and molecular studies (PCR based microsatellite instability and BRAF V600E mutation analysis). Morphological, immunohistochemical and molecular findings lead us to classify lymphoid stroma-rich advanced gastric carcinomas (n = 40/53) into two distinct entities originating from two different pathogenetic pathway: one is gastric carcinomas revealing predominantly medullary type morphology with defective DNA mismatch repair mechanism (n = 30/53) and the other is EBV associated carcinomas (n = 10/53). In addition, we suggest that biomarker based classification algorithms besides morphological evaluation are necessary to identify these two entities. Distinguishing these entities is crucial to apply different treatment strategies, including alternative treatments such as immunotherapy.

Micronodular Thymoma with Lymphoid Stroma: A Mediastinal Mass Masquerading as a Pericardial Mass.

A 61-year-old man presented to the emergency room with lower extremity edema. Physical exam was only remarkable for a diastolic murmur in the right carotid area and left lower extremity edema. Venous Doppler revealed a deep venous thrombosis in the left lower extremity. Chest computed tomography (CT) with intravenous contrast ruled out pulmonary embolism but showed a mediastinal mass adjacent to the pericardium. Further imaging with cardiac magnetic resonance imaging (CMR) and cardiac CT angiography (CCTA) enabled localization and evaluation of the structural characteristics of the mass. The decision was made to excise the mass due to increasing size compared with its measurements on prior chest CTs and a high degree of vascularization seen on CMR and CCTA, which was concerning for an enlarging arteriovenous malformation or a hemangioma. However, histopathologic analysis of the mass revealed it to be a micronodular thymoma.

Difference in the distribution of tumor-infiltrating CD8+ T cells and FOXP3+ T cells between micronodular thymoma with lymphoid stroma and micronodular thymic carcinoma with lymphoid stroma.

Micronodular thymoma with lymphoid stroma (MNT) is a rare thymic epithelial neoplasm subtype characterized by a micronodular tumor cell growth pattern and abundant lymphoid stroma. Micronodular thymic carcinoma with lymphoid stroma (MNCA) is considered as a malignant counterpart of MNT and exhibits a growth pattern similar to that of MNT but has histologic features reminiscent of thymic squamous cell carcinoma, such as cytologic atypia and CD5 and CD117 immunoexpression. Although both MNT and MNCA are characterized by abundant lymphoid stroma, it remains unknown whether there are differences in infiltrating lymphocytes between MNT and MNCA. We analyzed the immune microenvironment profile in eight MNT and three MNCA cases. The cell density of CD8-positive T cells was significantly higher in MNT than in MNCA, whereas that of FOXP3-positive T cells was significantly higher in MNCA than in MNT. There was no significant difference in the cell density of programmed death protein 1-positive T cells and programmed death ligand 1 expression between the MNT and MNCA cases. Our findings indicated that the immune microenvironment of MNCA differed from that of MNT and, compared with the T-cell profile of MNT, that of MNCA was more suppressive to patients' antitumor immune response.