Dysfunction of CD8+ T cells around tumor cells leads to occult lymph node metastasis in NSCLC patients.

Occult lymph node metastasis (OLNM) is one of the main causes of regional recurrence in inoperable N0 non-small cell lung cancer (NSCLC) patients following stereotactic ablation body radiotherapy (SABR) treatment. The integration of immunotherapy and SABR (I-SABR) has shown preliminary efficiency in mitigating this recurrence. Therefore, it is necessary to explore the functional dynamics of critical immune effectors, particularly CD8+ T cells in the development of OLNM. In this study, tissue microarrays (TMAs) and multiplex immunofluorescence (mIF) were used to identify CD8+ T cells and functional subsets (cytotoxic CD8+ T cells/predysfunctional CD8+ T cells (CD8+ Tpredys)/dysfunctional CD8+ T cells (CD8+ Tdys)/other CD8+ T cells) among the no lymph node metastasis, OLNM, and clinically evident lymph node metastasis (CLNM) groups. As the degree of lymph node metastasis escalated, the density of total CD8+ T cells and CD8+ Tdys cells, as well as their proximity to tumor cells, increased progressively and remarkably in the invasive margin (IM). In the tumor center (TC), both the density and proximity of CD8+ Tpredys cells to tumor cells notably decreased in the OLNM group compared with the group without metastasis. Furthermore, positive correlations were found between the dysfunction of CD8+ T cells and HIF-1α+CD8 and cancer microvessels (CMVs). In conclusion, the deterioration in CD8+ T cell function and interactive dynamics between CD8+ T cells and tumor cells play a vital role in the development of OLNM in NSCLC. Strategies aimed at improving hypoxia or targeting CMVs could potentially enhance the efficacy of I-SABR.

Prospective, longitudinal analysis of the gut microbiome in patients with locally advanced rectal cancer predicts response to neoadjuvant concurrent chemoradiotherapy.

BACKGROUND: Neoadjuvant concurrent chemoradiotherapy (nCCRT) is a standard treatment for locally advanced rectal cancer (LARC). The gut microbiome may be reshaped by radiotherapy through its effects on microbial composition, mucosal immunity, and the systemic immune system. We sought to clarify dynamic, longitudinal changes in the gut microbiome and blood immunomodulators throughout nCCRT and to explore the relationship of such changes with outcomes after nCCRT. METHODS: A total of 39 patients with LARC were recruited for this study. Fecal samples and peripheral blood samples were collected from all 39 patients before nCCRT, during nCCRT (at week 3), and after nCCRT (at week 5). The gut microbiota and the microbial community structure were analyzed by 16S rRNA sequencing of the V3-V4 region. Levels of blood immunomodulatory proteins were measured with a Millipore HCKPMAG-11 K kit and Luminex 200 platform (Luminex, USA). RESULTS: Cross-sectional and longitudinal analyses revealed that the gut microbiome profile and enterotype exhibited characteristic variations that could distinguish patients with good response (AJCC TRG classification 0-1) vs poor response (TRG 2-3) to nCCRT. Sparse partial least squares regression and canonical correspondence analyses showed multivariate associations between specific microbial taxa, host immunomodulatory proteins, immune cells, and outcomes after nCCRT. An integrated model consisting of baseline Clostridium sensu stricto 1 levels, fold changes in Intestinimonas, blood levels of the herpesvirus entry mediator (HVEM/CD270), and lymphocyte counts could predict good vs poor outcome after nCCRT [area under the receiver-operating characteristics curve (AUC)= 0.821; area under the precision-recall curve [AUPR] = 0.911]. CONCLUSIONS: Our results showed that longitudinal variations in specific gut taxa, associated host immune cells, and immunomodulatory proteins before and during nCCRT could be useful for early predictions of the efficacy of nCCRT, which could guide the choice of individualized treatment for patients with LARC.

Melanotic Xp11 translocation renal cancer: a report of a distinctive case and a review of the literature.

BACKGROUND: Melanotic Xp11 translocation renal cancer (TRC) is a newly described exceedingly rare tumor, and its characterization remains controversial. This study aimed to describe a case of distinctive melanotic Xp11 TRC and to elucidate its clinicopathological and molecular genetic features. CASE PRESENTATION: A 44-year-old Chinese female presented with a left renal mass. Abdominal ultrasonography and computed tomography (CT) scans revealed a 4.5 cm × 4.0 cm mass in the left kidney. Grossly, the well-demarcated mass was black with moderately firm consistency. Microscopic examination indicated that the tumor was characterized by the presence of nests and cords of polygonal cells with clear and granular eosinophilic cytoplasm, central round to oval nuclei and occasional nucleoli. Intracytoplasmic melanin was observed in approximately 45% of tumor cells. Uniquely, the tumor presented with intranuclear eosinophilic pseudoinclusions and thick-walled stromal blood vessels. IHC showed that tumor cells were diffusely positive for TFE3 and exhibited patchy and weak HMB45 staining. FISH confirmed the presence of TFE3 rearrangement. CONCLUSION: This case is the twentieth published case of melanotic Xp11 TRC. Moreover, the present patient had a favorable prognosis given that she was disease free at her 113-month postoperative follow-up. Our case adds to the small body of literature on these exceptionally rare tumors and widens their clinicopathological spectrum.

Renal myolipoosteoma: A distinctive lesion in a child.

We describe a distinctive renal tumor, a myolipoosteoma (MLO), in an 11-year-old boy who presented with a 6-month history of slight right flank intermittent pain. A gross examination revealed a well-defined, 5.5 cm mass with bone-like consistency. The lesion histologically featured an admixture of mature adipose tissue, spindle cells, and bony components. No atypia, mitotic activity, or pleomorphisms were observed in the tumor. The spindle cells were smooth muscle actin (SMA) and desmin positive but HMB45 and Melan-A negative, indicating that they were of a muscular nature and differed from that of angiomyolipoma (AML). The patient had no evidence of recurrence or metastasis 56 months postoperatively. We speculate that the present tumor, which to the best of our knowledge differs from all previously described tumors, is of nephrogenic rest (NR) origin and has a favorable prognosis.

Male occult breast cancer with axillary lymph node metastasis as the first manifestation: A case report and literature review.

RATIONALE: Occult breast cancer (OBC) is extremely rare in males with neither symptoms in the breast nor abnormalities upon imaging examination. PATIENT CONCERNS: This current case report presents a young male patient who was diagnosed with male OBC first manifesting as axillary lymph node metastasis. The physical and imaging examination showed no primary lesions in either breasts or in other organs. DIAGNOSES: The pathological results revealed infiltrating ductal carcinoma in the axillary lymph nodes. Immunohistochemical (IHC) staining was negative for estrogen receptor (ER), progesterone receptor (PR), cytokeratin (CK)20 and thyroid transcription factor-1 (TTF-1), positive for CK7, gross cystic disease fluid protein-15 (GCDFP-15), epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA), and suspicious positive for human epidermal receptor-2 (Her-2). On basis of IHC markers, particularly such as CK7, CK20 and GCDFP-15, and eliminating other malignancies, male OBC was identified in spite of negativity for hormone receptors. INTERVENTIONS: The patient underwent left axillary lymph node dissection (ALND) but not mastectomy. After the surgery, the patient subsequently underwent chemotherapy and radiotherapy. OUTCOMES: The patient is currently being followed up without any signs of recurrence. LESSONS: Carefully imaging examination and pathological analysis were particularly essential in the diagnosis of male OBC. The guidelines for managing male OBC default to those of female OBC and male breast cancer.

Ectopic hamartomatous thymoma: report of a case and review of literature.

Ectopic hamartomatous thymoma (EHT) is an exceedingly rare lesion that usually arises in the lower neck and mainly affects adult men. We present the clinicopathological features of a case of EHT in a 28-year-old Chinese male, together with a literature review. Ultrasound imaging and a computed tomography (CT) scan of the neck demonstrated a 3.0-cm well-defined nodule of heterogeneous density located within the left sternocleidomastoid muscle. The patient underwent a gross total resection of the tumor. Grossly, the well-demarcated, encapsulated mass had a predominantly solid and gray-white appearance admixed with microcystic foci filled with serous content and yellowish regions. The lesion consisted of an irregular admixture of spindle cells, epithelium, and mature adipose tissue. Immunohistochemistry showed that both the spindle cell and epithelial components were diffuse and had intense nuclear positivity for p63 and cytoplasmic reactivity for pan-cytokeratin, CK7, and CK19. The patient was followed for 18 months without any evidence of metastasis or recurrence.

Clinicopathological characteristics of xeroderma pigmentosum associated with keratoacanthoma in an infant.

A rare case of xeroderma pigmentosum coexisted with keratoacanthoma in an 18-month-old boy was reported. The boy was admitted with unequal size, irregularly shaped brown spots, patches and depigmentation spots on his face. A well-circumscribed hemispherical mass measuring 3 cm×3 cm with smooth surface and brown patches was observed beneath his left lower eyelid. Light microscopic examination of the skin lesions revealed epidermal hyperkeratosis, chronic inflammatory infiltration of the superficial dermal layer, and increases in melanocytes and melanin in the basal layer. The mass beneath the left lower eyelid was cup-shaped, consisting of proliferating squamous cells with a central keratin plug. The squamous epithelium was acanthotic with hypergranulosis. The adjacent epidermis formed exophytic projections resulting in a silhouette likened to lips. The patient was treated with a combination of antioxidant drugs, keeping the child from light and surgical excision of the mass. No recurrence has been observed.

Gradually elevated expression of Gankyrin during human hepatocarcinogenesis and its clinicopathological significance.

Gankyrin is an important oncoprotein that is overexpressed in human hepatocellular carcinoma (HCC). However, the gradual alteration of Gankyrin in successive stages during human HCC development and the mechanism of Gankyrin-mediated hepatocarcinogenesis remain largely unknown. In this study, we evaluated the pattern and level of Gankyrin protein expression using immunohistochemistry in various liver tissues, including normal liver, chronic hepatitis, cirrhosis, adenomatous hyperplasia (AH), and HCC tissues, to analyze its clinicopathological significance. Furthermore, we stably transfected the shRNA-Gan vector, which targets human Gankyrin, into HepG2 cells to assess the role of Gankyrin in cell proliferation and tumorigenicity. The expression level of Gankyrin in the cytoplasm, nucleus, and whole cell was gradually elevated during consecutive stages of hepatocarcinogenesis. The nuclear Gankyrin level in AH was significantly higher than that in normal liver, chronic hepatitis, and cirrhotic tissues. The cytoplasmic, nuclear, and total cellular Gankyrin expression levels in HCC were significantly correlated with capsular invasion and intrahepatic metastasis. Silencing Gankyrin expression using shRNA-Gan repressed tumor cell proliferation, tumorigenicity, migration, and invasion in vitro. Our findings demonstrate that Gankyrin is aberrantly expressed beginning at the initiation stage and plays an important role in the initiation, promotion, and progression of hepatocarcinogenesis.

Oncocytic meningioma: a case report and review of the literature.

Oncocytic meningioma is an uncommon variant of meningioma, with only 20 reported cases to date, that is histologically characterized by the presence of neoplastic cells with granular eosinophilic cytoplasm rich in mitochondria. We present the clinicopathological features of a case of oncocytic meningioma in a 49-year-old Chinese female, along with a literature review. Brain computed tomography and magnetic resonance imaging demonstrated a slightly hyperintense mass located in the right frontal region and attached to the dura. In addition, it was homogeneously enhanced following contrast administration. She underwent gross total surgical resection of the tumor and adjacent dura. Grossly, the well-demarcated, nonencapsulated mass had a solid and tan-white appearance with soft and rubbery consistency. The lesions were composed primarily of sheets, nests, and cords of large polygonal bland cells with finely granular eosinophilic cytoplasm rich in mitochondria. Mitotic figures were rare, and necrosis was absent. There was no infiltration of the dura or brain cortex. Immunohistochemical staining revealed that the neoplastic cells were positive for vimentin, epithelial membrane antigen, antimitochondrial antibody, and progesterone receptor, whereas MIB-1 stained only approximately 1% of the tumor cells. This is the first known report of an oncocytic meningioma arising in a Chinese patient. The patient was followed for 19 months without any evidence of metastasis or recurrence.

Sarcomatoid carcinoma of the stomach with osteoclast-like giant cells.

Carcinomas with osteoclast-like giant cells (OGCs) are a rare type of malignant tumor that is histologically characterized by the presence of multinucleated giant cells that resemble osteoclasts mixed with poorly differentiated adenocarcinoma cells. In this study, we report the clinicopathological and immunohistochemical features of a gastric sarcomatoid carcinoma with OGCs in a 37-year-old male. An abdominal CT scan demonstrated a large mass, measuring 15 cm × 10 cm, in the lesser curvature of the stomach. Microscopic examination revealed that the tumor was composed of sarcomatoid and carcinomatous elements with infiltrating OGCs. Immunohistochemical analysis showed that the sarcomatoid and carcinomatous elements were both variably positive for CK7 and EMA. The sarcomatoid components were also vimentin and SMA positive. This is the first report of a gastric sarcomatoid carcinoma with OGCs. The present tumor has progressed rapidly with extensive perigastric involvement and multiple intrahepatic metastases.

Adenocarcinoma arising from a gastric duplication cyst.

Malignant transformation in a gastric duplication cyst (GDC) is extremely rare, with only eight reported cases to date. An additional case of an adenocarcinoma arising from a GDC in a 25-year-old male is reported here. Ultrasonography and computed tomography (CT) scans detected a well-defined cyst arising from the greater curvature of the stomach. The patient was submitted to en-bloc resection of the mass with total gastrectomy and regional lymphadenectomy. At the time of laparotomy, the unilocular cyst was full of a thick substance and had no association with the gastric lumen. Microscopic examination revealed that the cystic mass had a well-formed cyst wall with an inner mucosal lining, submucosal layer, muscularis propria, and outer serosal layer. The inner cyst was lined by gastric mucosa. A mediated differentiated adenocarcinoma was found in the duplication cyst, which had invaded the serosa of the cyst wall and the gastric muscular wall. To our knowledge, this is the youngest and only asymptomatic patient in whom neoplastic GDC changes have been reported.

Lipomatous hemangiopericytoma of the stomach: a case report and a review of literature.

Lipomatous hemangiopericytomas (LHPCs) are rare soft-tissue tumors that are histologically characterized by hemangiopericytomatous vasculature and the presence of mature adipocytes. We present the clinicopathological features of a case of gastric LHPC in a 56-year-old female, along with a literature review. Endoscopy and endoscopic ultrasound showed a submucosal tumor 0.8 cm across in the greatest dimension in the lesser curvature side of the gastric antrum. Grossly, the well-defined mass had a solid and tan-white cut surface admixed with myxoid regions and yellowish areas. Histological examination revealed a submucosal well-circumscribed lesion composed of cellular nodules with the classic appearance of an hemangiopericytoma admixed with clusters and lobules of mature adipocytes. The ill-defined tumor cells had weakly eosinophilic cytoplasm and contained spindled nuclei with occasional small nucleoli. Nuclei atypia and mitoses were absent, and no cellular atypia, necrosis or vascular invasion was observed. Immunohistochemistry showed that the tumor cells were diffusely positive for CD34, CD99, and vimentin and were focally reactive for bcl-2. This is the first known report of an LHPC in the stomach. The patient was followed for 12 mo without any evidence of metastasis or recurrence.

[Large cell calcifying Sertoli cell tumor of the testis: a clinicopathological observation].

OBJECTIVE: To investigate the clinicopathological characteristics of large cell calcifying Sertoli cell tumor (LCCSCT) of the testis. METHODS: We studied a case of LCCSCT by light microscopy, Western blotting and immunohistochemistry, reviewed relevant literature, and analyzed the clinical, morphological and immunohistochemical features, treatment and prognosis of the tumor. RESULTS: The patient was a 25 years old man. Pathohistologically, the tumor was characterized by a mass of polygonal tumor cells in a tubular and trabecular growth pattern, with abundant acidophilic cytoplasm, enlarged vesicular nuclei, and extensive calcified debris in stroma. The tumor cells were positive for inhibin, S-100, vimentin and alcian blue, but negative for PLAP, SMA, CK, AFP and periodic acid-Schiff (PAS) reaction. CONCLUSION: LCCSCT is a rare testicular sex cord stromal tumor. Its diagnosis is based on immunohistochemical staining, and it is to be differentiated from other lesions of the testis, including seminoma, Leydig cell tumor, Sertoli cell node, and androgen insensitivity syndrome. For the treatment of LCCSCT, surgical resection often has a good prognosis.

Association of clinicopathological features with UbcH10 expression in colorectal cancer.

PURPOSE: UbcH10 is the cancer-related E2 ubiquitin-conjugating enzyme, and its overexpression has been demonstrated in a variety of malignancies. The aim of this study is to investigate the association of UbcH10 gene expression with the carcinogenesis and tumor progression of colorectal cancer. METHODS: The expression levels of UbcH10 in human malignant colorectal carcinoma tissues and their adjacent normal tissues were examined using real-time quantitative RT-PCR and immunohistochemical analysis. The correlations of UbcH10 expression to the clinicalpathologic characteristics of the colorectal cancer were analyzed. Cell proliferation and Matrigel invasion assays were performed in HT-29 cells transfected with UbcH10 expression plasmid pcDNA3.1-UbcH10, UbcH10 RNA interference vector pUbcH10-RNAi as well as their control vectors. RESULTS: Our study demonstrated that the expression of UbcH10 in colorectal carcinoma tissues was significantly higher than that in non-cancerous tissues (P < 0.01), and the UbcH10 overexpression was related to the degree of tumor differentiation and lymph node metastasis of colorectal cancer patients (P < 0.05). In vitro, the overexpression of UbcH10 promoted cell proliferation and tumor invasiveness, but the downregulation of UbcH10 expression significantly reduced the growth rate and the invasiveness activity of tumor cell line. CONCLUSIONS: Our study suggests that the overexpression of UbcH10 gene plays a critical role in the carcinogenesis and tumor progression of colorectal cancer. It may be a new marker in diagnosis and prognosis of colorectal cancer, and the inhibition of UbcH10 may be a therapeutic potential for the treatment of colorectal cancer.

Renal cell carcinoma associated with Xp11.2 translocations, report of a case.

Renal cell carcinomas (RCCs) associated with Xp11.2 translocations (Xp11.2 translocation RCCs) are rare and occur predominantly in children and adolescents. A case of such tumor in a 12-year boy is reported. Grossly the cut surface of the ill-defined mass was polychromatic, containing areas of hemorrhage and necrosis. Microscopically, the tumor was composed of epithelioid cells with clear to weakly eosinophilic cytoplasm arranged in nested, alveolar, and pseudopapillary formations. Immunohistochemically, the neoplastic cells were positive for transcription factor E3 and CD10. We concluded that this case was an Xp11.2 translocation RCC.