The Rarity of Metastasis to the Spleen - a Phenomenon with an Unknown Mechanism.

The review analyses the frequency of malignant tumors metastasizing to the spleen. The facts are presented of a higher frequency of metastasis to the spleen in the presence of multiple metastases to other organs and the extreme rarity of isolated metastases to the spleen. Despite the rarity of spleen metastases, their frequency varies depending on the nosological form of the malignancy. The data about clinical manifestations of spleen metastases and positive effects of splenectomy in these cases are presented. The hypotheses explaining the rarity of metastases to the spleen are analyzed. Emphasis is placed on the multiple immune functions of the spleen, including the development of immunogenesis and tolerance, and the possible role of these processes in inhibiting the development of spleen metastases. However, to date, there is no complete understanding of the mechanisms of spleen metastasis inhibition. The spleen is an area where antimetastatic microenvironment is naturally formed. Understanding of the mechanisms inhibiting the development of metastases in the spleen and underlying the failure of this function in cases where metastases do occur could arm oncologists with a new strategy to prevent metastasis to any organ. Targeted research in this field is required.

Case report of isolated synchronous multiple splenic metastases from rectal cancer: A case report and brief review of the literature.

INTRODUCTION: Isolated splenic metastasis emanating from colorectal cancer is an extremely rare finding, which usually indicates widely disseminated and multiple metastatic cancer. There have only been 39 cases of isolated splenic metastasis reported in the English literature to date. PATIENT CONCERNS: An 84-year-old female patient presented to our department with dark-red bloody stool that had persisted for 1 month and with an increased serum carcinoembryonic antigen (CEA) level. DIAGNOSES: A colonoscopy showed a rectal mass located 3 cm from the anal margin, which was 45 mm in diameter. The patient was diagnosed with rectal cancer with splenic metastases by abdomen computed tomography. INTERVENTIONS: The patient underwent a radical resection of rectal cancer and splenectomy, and the postoperative histopathology confirmed that the splenic lesions were derived from the adenocarcinoma of the rectum. OUTCOMES: After surgical treatment, the patient recovered well and was recommended for further chemotherapy. CONCLUSIONS: In addition to revealing a rare case, we also performed a literature review, including a brief discussion about the atypical isolated splenic metastasis from colorectal cancer. Our findings enrich the database of this rare clinical entity and provide experience in the management of splenic metastasis.

Isolated Spleen Metastases of Endometrial Cancer: A Case Report.

BACKGROUND: Isolated splenic metastases from endometrial cancer, which is a relatively common malignancy, are extremely rare findings; to date, only 14 cases have been reported in the literature. CASE SUMMARY: We report a patient with isolated splenic metastases of endometrial cancer 3 years after radical surgery of the primary tumor. The patient was successfully treated by splenectomy and six cycles of paclitaxel. Fifty months after splenectomy, she was alive and well, and with no evidence of disease. CONCLUSION: Isolated spleen metastasis of endometrial cancer is very rare. Radical surgery and adjuvant therapy may offer excellent long-term survival.

Solitary Splenic Metastasis From Endometrial Carcinoma Revealed on FDG PET/CT.

ABSTRACT: Solitary splenic metastasis from endometrial carcinoma is rare. We report a case of imaging findings of solitary splenic metastasis in a 53-year-old woman who underwent resection surgery of endometrial carcinoma of uterus 1 year ago. On FDG PET/CT, it presented as a solitary soft tissue mass with an SUVmax of 18.44. The postoperative pathology supported metastasis from endometrial carcinoma.

[Isolated splenic metastasis from colorectal cancer]. / Izolirovannyi metastaz kolorektal'nogo raka v selezenku: klinicheskii sluchai.

Splenic metastases are a rare finding and usually associated with advanced cancer. At the same time, isolated splenic metastases are an exception. The authors report a 62-year-old woman with isolated splenic metastasis from colon carcinoma in 28 months after surgery. Splenectomy was successfully performed.

[A Case of Synchronous Solitary Splenic Metastasis of Sigmoid Colon Cancer Treated with Laparoscopic Resection].

An 82-year-old woman presented to our hospital with chief complaints of lower abdominal pain and nausea. Contrast- enhanced CT showed ileus of sigmoid colon cancer and a solitary splenic tumor. A metallic stent was placed for the primary lesion. FDG-PET showed high FDG accumulation in the solitary splenic tumor, and synchronous solitary splenic metastasis was diagnosed. Laparoscopic sigmoid colectomy and laparoscopic splenectomy were performed without changing the intraoperative position or port arrangement. Postoperative progress was favorable. The patient was discharged 9 days after surgery, and no sign of recurrence has been observed to date, at 4 months after surgery. Solitary splenic metastasis of colorectal cancer is extremely rare. This is the first case report of synchronous solitary splenic metastasis of colorectal cancer treated with laparoscopic resection in Japan. This procedure is considered effective and minimally invasive. We review and discuss the Japanese literature on this rare disease.

A Rare Case of Progressive Malignant Triton Tumor With Rare Somatic Mutation in TSC2 Gene.

BACKGROUND: Malignant triton tumor (MTT) is a rare subtype of malignant peripheral nerve sheath tumor with additional rhabdomyolysis differentiation that shows rapid progression and poor clinical outcomes. CASE REPORT: We report the case of an adult male with a metastatic MTT. Despite extensive counseling, the patient initially refused recommended treatment. Upon disease progression, the patient was admitted to our institution and multiple distant organ metastases were found. The patient underwent an above-knee amputation followed by palliative chemotherapy. The patient died a few months later due to rapid disease progression. CONCLUSION: To our knowledge, this is the first report of a case of MTT with multiple splenic metastases. We also describe the first finding of a frame-shift mutation in the tuberous sclerosis complex 2 (TSC2) gene in a patient with MTT. Because of limited clinical experience and the lack of clinical trials, the effects of chemotherapy and radiation therapy for MTT remain controversial. However, given the aggressive nature of these tumors and the tendency for early recurrence and metastasis, prompt diagnosis and early surgical treatment are crucial for the best outcomes.

Circulating Small Extracellular Vesicles Activate TYRO3 to Drive Cancer Metastasis and Chemoresistance.

Extracellular vesicles (EV) in the tumor microenvironment have emerged as crucial mediators that promote proliferation, metastasis, and chemoresistance. However, the role of circulating small EVs (csEV) in cancer progression remains poorly understood. In this study, we report that csEV facilitate cancer progression and determine its molecular mechanism. csEVs strongly promoted the migration of cancer cells via interaction with phosphatidylserine of csEVs. Among the three TAM receptors, TYRO3, AXL, and MerTK, TYRO3 mainly interacted with csEVs. csEV-mediated TYRO3 activation promoted migration and metastasis via the epithelial-mesenchymal transition and stimulation of RhoA in invasive cancer cells. Additionally, csEV-TYRO3 interaction induced YAP activation, which led to increased cell proliferation and chemoresistance. Combination treatment with gefitinib and KRCT-6j, a selective TYRO3 inhibitor, significantly reduced tumor volume in xenografts implanted with gefitinib-resistant non-small cell lung cancer cells. The results of this study show that TYRO3 activation by csEVs facilitates cancer cell migration and chemoresistance by activation of RhoA or YAP, indicating that the csEV/TYRO3 interaction may serve as a potential therapeutic target for aggressive cancers in the clinic. SIGNIFICANCE: These findings demonstrate that circulating extracellular vesicles are a novel driver in migration and survival of aggressive cancer cells via TYRO3 activation. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/13/3539/F1.large.jpg.

Immune remodeling triggered by photothermal therapy with semiconducting polymer nanoparticles in combination with chemotherapy to inhibit metastatic cancers.

Photothermal therapy (PTT) based on semiconducting polymer nanoparticles (SPNs) is a promising strategy to treat solid tumors, but its ability to combine with chemotherapy for immune remodeling to efficiently suppress metastatic cancers has rarely been studied. Here, we demonstrate that PTT combined with chemotherapy can efficiently elicit immunity to suppress metastatic tumor growth. Specifically, we rationally designed a new SPN (PDPSe NPs) as a photothermal agent for PTT with a large mass extinction coefficient in the near-infrared region (e.g., 44.9 L g-1 cm-1 at 808 nm), high photothermal conversion efficiency (62.5%) and excellent biocompatibility. A hypoxia-activated anti-tumor drug, tirapazamine (TPZ), was selected for chemotherapy. Strikingly, the combination therapy not only induced tumor cell death in the primary tumor, but also effectively suppressed the growth of distant tumors (mimicking metastatic tumors) without PTT. Importantly, the combined therapies exhibit synergistic effects on immune remodeling. Immunofluorescence data suggest that the inhibition of metastatic tumor growth is attributed to the immune remodeling triggered by PTT and chemotherapy. This work demonstrates a new paradigm of utilizing PTT together with hypoxia-activated drugs to effectively retard metastatic tumor growth.

Peritoneal melanosis associated with metastatic melanoma previously treated with targeted and immune checkpoint inhibitor therapy.

Peritoneal melanosis is an uncommon benign condition, the pathophysiology of which is unclear. Macroscopically, it appears as diffuse dark brown or black pigmentation within the peritoneum, mimicking more sinister conditions such as metastatic melanoma. It has been described in a variety of contexts, but only exceedingly rarely in association with metastatic melanoma, with only two previous published case reports. We present a case of peritoneal melanosis associated with metastatic melanoma involving the spleen, previously treated with targeted and immune checkpoint inhibitor therapy. With increasing reports of melanoma regression manifesting as cutaneous tumorous melanosis in patients treated with immune checkpoint inhibitors, we postulate that, similarly, immunotherapy and tumour regression might have a role to play in the pathogenesis of the peritoneal pigmentation in this case.

Solitary Splenic Metastasis of Lung Cancer Presenting as Benign Cystic Disease.

Solitary splenic metastasis from primary lung cancer is extremely rare. Here, we demonstrated a solitary splenic metastasis of primary lung cancer that was difficult to distinguish from benign cystic disease. A 69-year-old-female was diagnosed as middle lobe lung cancer. Although preoperative abdominal computed tomography (CT) demonstrated a low-density splenic nodule, fluorodeoxyglucose-positron emission tomography (FDG-PET) revealed no fluorodeoxyglucose uptake in the splenic nodule. Therefore, the nodule was diagnosed as benign cystic disease and middle lobe lobectomy was performed. Postoperative pathologic examination demonstrated papillary-predominant adenocarcinoma with mucin, and the tumor was diagnosed as primary lung cancer. However, the splenic nodule continued to increase postoperatively. Splenectomy was undergone 30 months after the pulmonary resection and the splenic tumor was diagnosed as the splenic metastasis of lung cancer. In the 24 months since the splenectomy, no recurrence has been observed in the absence of treatment. Splenectomy was an effective treatment for solitary splenic metastasis of lung cancer in this case. FDG uptake in the splenic tumor was not evident due to marked mucus production.

Strobilanthes crispus bioactive subfraction inhibits tumor progression and improves hematological and morphological parameters in mouse mammary carcinoma model.

ETHNOPHARMACOLOGICAL RELEVANCE: Locally known as 'pecah batu', 'bayam karang', 'keci beling' or 'batu jin', the Malaysian medicinal herb, Strobilanthes crispus (S. crispus), is traditionally used by the local communities as alternative or adjuvant remedy for cancer and other ailments and to boost the immune system. S. crispus has demonstrated multiple anticancer therapeutic potential in vitro and in vivo. A pharmacologically active fraction of S. crispus has been identified and termed as F3. Major constituents profiled in F3 include lutein and ß-sitosterol. AIM OF THE STUDY: In this study, the effects of F3, lutein and ß-sitosterol on tumor development and metastasis were investigated in 4T1-induced mouse mammary carcinoma model. MATERIALS AND METHODS: Tumor-bearing mice were fed with F3 (100 mg/kg/day), lutein (50 mg/kg/day) and ß-sitosterol (50 mg/kg/day) for 30 days (n = 5 each group). Tumor physical growth parameters, animal body weight and development of secondary tumors were investigated. The safety profile of F3 was assessed using hematological and histomorphological changes on the major organs in normal control mice (NM). RESULTS: Our findings revealed significant reduction of physical tumor growth parameters in all tumor-bearing mice treated with F3 (TM-F3), lutein (TM-L) or ß-sitosterol (TM-ß) as compared with the untreated group (TM). Statistically significant reduction in body weight was observed in TM compared to the NM or treated (TM-F3, TM-L and TM-ß) groups. Histomorphological examination of tissue sections from the F3-treated group showed normal features of the vital organs (i.e., liver, kidneys, lungs and spleen) which were similar to those of NM. Administration of F3 to NM mice (NM-F3) did not cause significant changes in full blood count values. CONCLUSION: F3 significantly reduced the total tumor burden and prevented secondary tumor development in metastatic breast cancer without significant toxicities in 4T1-induced mouse mammary carcinoma model. The current study provides further support for therapeutic development of F3 with further pharmacokinetics studies.

Metástasis esplénica secundaria a carcinoma mamario / Splenic metastasis secondary to breast cancer

INTRODUCCIÓN: Los tumores de bazo primarios o metastásicos suponen menos del 0,96% de todas las metástasis. CASO CLÍNICO: Mujer de 80 años de edad intervenida 3,5 años antes por carcinoma ductal infiltrante con tratamiento neoadyuvante. Durante el seguimiento se encontró en PET-TAC recidiva tumoral en hilio esplénico. Se realizó esplenectomía laparoscópica que fue informada como adenocarcinoma de origen mamario. DISCUSIÓN: Las metástasis esplénicas son infrecuentes, suelen manifestarse como esplenomegalia asociadas a molestias abdominales. Los tumores esplénicos malignos presentan fiebre, síndrome constitucional, derrame pleural y caquexia. El diagnóstico de metástasis esplénicas suele realizarse durante el seguimiento oncológico con tomografía computarizada (TC). El tratamiento es la resección quirúrgica, aunque no existen protocolos para el tratamiento de las metástasis esplénicas. La supervivencia tras la esplenectomía por metástasis aumenta. CONCLUSIONES: La esplenectomía ante metástasis esplénicas es el tratamiento realizado habitualmente ante estos casos

INTRODUCTION: Both primitive and metastatic splenic tumours represent less than 0.96% of all metastases. CLINICAL CASE: We report the case of an 80-year-old woman, who had undergone surgery for invasive ductal carcinoma 3.5 years previously with neoadjuvant treatment. During follow-up, PET-CT revealed tumour recurrence in the splenic hilum. Laparoscopic splenectomy was performed, which was reported as an adenocarcinoma of mammary origin. DISCUSSION: Splenic metastases are infrequent, and usually present as splenomegaly associated with abdominal discomfort. The symptoms of malignant splenic lesions are fever, constitutional syndrome, pleural effusion, and cachexia. Diagnosis of splenic metastases is usually carried out during oncological follow-up with computed tomography. Treatment is surgical resection, although there are no protocols for the treatment of splenic metastases. Survival increases after splenectomy due to metastasis. CONCLUSIONS: Splenectomy for splenic metastases is the most common treatment in these cases