Paraneoplastic leukocytosis secondary to carcinosarcoma: a report of two cases and literature review.

BACKGROUND: Neutrophilia is an increase in the number of neutrophils over 7.5×103/µL. An increase in leukocytes over 50×103/µL is called a leukemoid reaction; and when it is associated with a solid tumor, it is considered a paraneoplastic syndrome called paraneoplastic leukemoid reaction (PLR). It is a very rare clinical condition and it is very unusual for it to be associated with carcinosarcoma. We present two cases of a leukemoid reaction observed in the Medical Oncology Department of the University Hospital of Salamanca between May and September 2023. The main objectives of our article are to describe the unusual appearance of paraneoplastic leukocytosis at the diagnosis of carcinosarcoma carcinosarcoma, explain in a detailed way its diagnostic procedure and to show the poor prognosis to which it is associated. CASE DESCRIPTION: In our presentation, we describe two similar cases: first of all, a 60-year-old woman without relevant medical history. She was referred by her primary physician to the Department of Internal Medicine in August 2023 with asthenia, lumbar pain, and weight loss of 12 kg of 3 months of evolution. The physical examination revealed a palpable hypogastric mass. An abdominal, pelvic, and thoracic computed tomography (CT) scan revealed a heterogenous solid mass with necrotic areas originating in the uterus. The anatomopathological diagnosis was carcinosarcoma. The patient showed a progressive worsening in her renal function associated with hyperviscosity secondary to hyperleukocytosis caused by 170×103/µL neutrophils. In the second case we describe the diagnosis of a PLR secondary to a kidney carcinosarcoma. When the patient started chemotherapy, he presented 55.08×103/µL leukocytes, 53.16×103/µL neutrophils. Eight days after receiving chemotherapy, the patient was admitted as an emergency with oligoanuria and decreased consciousness. He presented creatinine 6.25 mg/dL, phosphate 12.4 mg/dL, leukocytes 1.05×103/µL, and neutrophils 0.71×103/µL. The clinical diagnosis was acute exacerbation of multifactorial mixed (renal and prerenal) chronic kidney disease associated with tumor lysis syndrome and grade 3 neutropenia. The patient presented a poor evolution, dying after 2 months. CONCLUSIONS: PLR is a severe paraneoplastic syndrome associated with different types of solid tumors. Its appearance at the time of diagnosis of a tumor implies a poor vital prognosis.

Multiple sarcomatoid carcinomas in the small intestine with perforation: A case report and literature review.

RATIONALE: Sarcomatoid carcinoma of the small intestine is an exceedingly rare and aggressive malignancy, often diagnosed at advanced stages with a poor prognosis. This study documents a detailed case of sarcomatoid carcinoma of the small intestine, highlighting the diagnostic challenges and treatment approaches, underscored by a comprehensive review of related literature. Given the rarity of this condition, our report aims to enrich the existing diagnostic and treatment frameworks for this malignancy, emphasizing the necessity for early detection and intervention strategies. By presenting this case in conjunction with a literature review, we seek to shed light on the elusive nature of sarcomatoid carcinoma in the small intestine and propose avenues for improving patient outcomes. PATIENT CONCERNS: Case presentation A 61-year-old male patient initially presented with recurrent abdominal pain and gastrointestinal symptoms. Initial abdominal computed tomography (CT) scans and gastrointestinal endoscopy revealed only inflammatory and hyperplastic changes in the duodenum and jejunum, with a diagnosis of intestinal obstruction. Two years later, due to gastrointestinal perforation, the patient was hospitalized again. DIAGNOSES: CT scans and other examinations revealed small intestinal lesions. Four small intestinal lesions were surgically removed, and pathology and immunohistochemistry confirmed sarcomatoid carcinoma of the small intestine. A short time later, enhanced CT scans revealed metastatic lesions in the hepatic portal and adrenal glands. INTERVENTIONS: After surgery, the gastrointestinal function gradually recovered, and the patient was discharged from the hospital on a semiliquid diet. No further treatment such as radiotherapy or chemotherapy was administered postoperatively. OUTCOMES: Five months after the surgery, the patient died due to brain metastasis. LESSONS: The study outcomes reveal the aggressive nature of sarcomatoid carcinoma of the small intestine, characterized by rapid progression and poor prognosis despite surgical interventions. The patient condition rapidly deteriorated, leading to metastasis and death within 5 months postsurgery. These findings underscore the critical need for early detection and possibly innovative treatment approaches to improve survival rates. This case also highlights the potential for gastrointestinal sarcomatoid carcinoma to metastasize to distant organs, including the brain, suggesting a propensity for hematogenous spread.

A case of ovarian carcinosarcoma with a germline pathogenic variant of BRCA2 involving a perforated appendix with an abscess.

We report a case of rare and aggressive ovarian carcinosarcoma with a germline pathogenic BRCA2 variant. A patient with a history of breast cancer who developed an inflammatory ovarian tumor with peritonitis carcinomatosis involving the appendix suffered from cachexia. Following three cycles of weekly paclitaxel and carboplatin chemotherapy, emergency surgery was required owing to sepsis. Bilateral salpingo-oophorectomy, total hysterectomy, appendectomy, and small intestine adhesiolysis were performed. Histologically, the tumor comprised an admixture of carcinomatous and sarcomatous components, with involvement of the appendix, which had caused perforation and abscess formation. The final diagnosis was ovarian carcinosarcoma with a germline pathogenic BRCA2 variant, c.658_659del (p.Val220fs). The patient responded completely to adjuvant chemotherapy. A combination of chemotherapy and surgery might be beneficial to patients with ovarian carcinosarcoma and germline pathogenic BRCA2 variants with a poor general condition. This is the first report of ovarian carcinosarcoma with a germline pathogenic BRCA2 variant that responded favorably to chemotherapy.

Cachexia causes time-dependent activation of the inflammasome in the liver.

BACKGROUND: Cachexia is a wasting syndrome associated with systemic inflammation and metabolic disruption. Detection of the early signs of the disease may contribute to the effective attenuation of associated symptoms. Despite playing a central role in the control of metabolism and inflammation, the liver has received little attention in cachexia. We previously described relevant disruption of metabolic pathways in the organ in an animal model of cachexia, and herein, we adopt the same model to investigate temporal onset of inflammation in the liver. The aim was thus to study inflammation in rodent liver in the well-characterized cachexia model of Walker 256 carcinosarcoma and, in addition, to describe inflammatory alterations in the liver of one cachectic colon cancer patient, as compared to one control and one weight-stable cancer patient. METHODS: Colon cancer patients (one weight stable [WSC] and one cachectic [CC]) and one patient undergoing surgery for cholelithiasis (control, n = 1) were enrolled in the study, after obtainment of fully informed consent. Eight-week-old male rats were subcutaneously inoculated with a Walker 256 carcinosarcoma cell suspension (2 × 107 cells in 1.0 mL; tumour-bearing [T]; or phosphate-buffered saline-controls [C]). The liver was excised on Days 0 (n = 5), 7 (n = 5) and 14 (n = 5) after tumour cell injection. RESULTS: In rodent cachexia, we found progressively higher numbers of CD68+ myeloid cells in the liver along cancer-cachexia development. Similar findings are described for CC, whose liver showed infiltration of the same cell type, compared with both WSC and control patient organs. In advanced rodent cachexia, hepatic phosphorylated c-Jun N-terminal kinase protein content and the inflammasome pathway protein expression were increased in relation to baseline (P < 0.05). These changes were accompanied by augmented expression of the active interleukin-1ß (IL-1ß) form (P < 0.05 for both circulating and hepatic content). CONCLUSIONS: The results show that cancer cachexia is associated with an increase in the number of myeloid cells in rodent and human liver and with modulation of hepatic inflammasome pathway. The latter contributes to the aggravation of systemic inflammation, through increased release of IL-1ß.

[Ovarian Carcinosarcoma Associated with Cowden Syndrome-A Case Report].

Cowden syndrome is a rare autosomal dominant disorder characterized by multiple hamartomas in various tissues, including the skin, mucous membranes, and gastrointestinal tract. Germline mutations of the PTEN tumor suppressor gene are responsible for Cowden syndrome. Cowden syndrome is associated with an increased risk of breast, thyroid, renal and uterine cancers; however, ovarian cancer rarely develops in women with Cowden syndrome, although somatic PTEN mutation often occurs in some types of ovarian carcinomas. Herein we report the first case of ovarian carcinosarcoma that developed in a woman with Cowden syndrome. A 55-year-old woman with a history of breast cancer, thyroid goiter, and palatal papillomatosis presented with pelvic distention. CT scan revealed a pelvic tumor suggesting ovarian cancer. She underwent a total abdominal hysterectomy, a bilateral salpingo-oophorectomy, and an omentectomy, but the surgical cytoreduction was suboptima( l >2 cm residual disease). Pathological examination showed a mixed tumor composed of high-grade carcinoma and heterologous sarcoma. Immunohistochemically, tumor cells were positive for p53. She was diagnosed with stage ⅢC ovarian carcinosarcoma. Genetic testing detected a PTEN variant, confirming the diagnosis of Cowden syndrome. She received paclitaxel/ carboplatin chemotherapy. However, no response was observed and she died of disease 2 months postoperatively.

Pulmonary carcinosarcoma with an aggressive heterologous angiosarcoma component: A case report.

Pulmonary carcinosarcomas are rare biphasic lung tumors comprised of malignant epithelial and malignant mesenchymal components. The most common heterologous sarcomatous elements are osteosarcoma, rhabdomyosarcoma, and chondrosarcoma; a heterologous angiosarcoma component in a pulmonary carcinosarcoma is exceedingly rare. We report a case of a pulmonary carcinosarcoma containing adenocarcinoma, squamous cell carcinoma, undifferentiated malignant spindle cell, and heterologous angiosarcoma components. The patient, a 64-year-old woman, had initially presented to medical attention with hemoptysis. Although the tumor was thought to be confined to the lung at resection (pT3N0), she developed multiple metastatic foci within 3 weeks of lobectomy and required the evacuation of an intraparenchymal left occipital hematoma secondary to a hemorrhagic intra-axial focus of metastatic carcinosarcoma. She died 6 weeks after her primary lung resection from rapidly progressive metastatic disease. We hope the description and discussion provided herein will further the medical community's understanding of this rare malignancy.

Carcinosarcoma and sarcomatoid carcinoma of the stomach: Two case reports.

RATIONALE: Carcinosarcoma and sarcomatoid carcinoma of the stomach are rare, malignant, and biphasic tumors with high mortality. The differential diagnosis of these 2 diseases remains challenging. In the present study, we present 2 cases of carcinosarcoma and sarcomatoid carcinoma of the stomach. PATIENT CONCERNS: A 54-year-old woman was admitted with complaints of epigastric pain for 4 months, but she became serious for 10 days accompanied by melena. A 75-year-old man was admitted with complaints of epigastric pain for 1 month. DIAGNOSIS: The female had a Borrmann type III irregular ulcerative lesion (5.0 × 4.0 × 1.0 cm) originating from the gastric antrum. The male had Borrmann type I tumor polypoid exophytic (5.0 × 4.0 × 2.0 cm) in the fundus of stomach near the cardia. Both cases were identified as malignant neoplasms by endoscopic biopsy and further confirmed by performing laparoscopic proximal gastrectomy, esophagogastrostomy, and palliative distal subtotal gastrectomy. The postoperative histopathological morphology and immunohistochemistry studies revealed sarcomatoid carcinoma for the female and gastric carcinosarcoma for the male respectively. INTERVENTIONS: The female patient subsequently underwent laparoscopy-assisted radical distal gastrectomy for gastric cancer followed by systemic chemotherapy with oxaliplatin plus tegafur. The male patient underwent laparoscopic proximal gastrectomy and esophagogastrostomy were performed. OUTCOMES: The female had a mixture of a little poorly-differentiated adenocarcinoma and abundant sarcomatoid spindle cell elements, and is still alive healthy up to date for 2 and a half years after surgery by phone follow-up. The male patient had both adenocarcinoma and fibrosarcoma in a single tumor, and died 1 month after the operation. LESSONS: The present study provides insight into the clinical findings, differential diagnosis, and prognosis of carcinosarcomas and sarcomatoid carcinomas of the stomach. More cases are needed for further studies in the future.

Intramedullary spinal cord metastases: Report of three cases and review of the literature.

Intramedullary spinal cord metastases (ISCM) is a rare, but devastating complication of malignant disease. Prognosis is poor, with an overall median survival (OS) of 4 months from the time of diagnosis. Yet, ISCMs are being increasingly diagnosed, related to advances and increased use of imaging and therapies that prolong survival in patients with cancer. Prompt and accurate diagnosis of ISCM is necessary for effective treatment, and magnetic resonance imaging (MRI) is the preferred imaging technique. The optimal management of these patients is controversial because of the multitude of clinical circumstances and the lack of controlled studies on the efficacy of the different therapeutic approaches. Increased awareness of this rare entity may lead to an earlier diagnosis at a stage when neurological deficits are reversible, and therefore, more effective palliation may be achieved. Therefore, we carried out this retrospective research of 3 observations of ISCM, associated with a detailed review of the literature describing the diagnostic, therapeutic and evolutionary characteristics of this special rare entity.

Carcinosarcoma of the extrahepatic bile duct: an unusual cause of obstructive jaundice.

In relation to the article published in this journal by Guzmán describing a case of ampulla of Vater carcinosarcoma, we present a case of extrahepatic bile duct carcinosarcoma. A neoplasm described in different anatomical locations with an exceptional origin in the bile duct.

[Non endometroid endometrial cancer guidelines evaluation: A multicentric retrospective study]. / Évaluation de l'application des recommandations des cancers de l'endomètre de type 2 : étude rétrospective multicentrique.

INTRODUCTION: Non endometrioid endometrial cancer are infrequent and have poor prognosis. The aim of the study was to evaluate non endometrioid endometrial cancer managment by evaluating endometrial cancer guidelines application. MATERIAL AND METHODS: This multicentric retrospective study enrolled non endometrioid endometrial cancer between January 2009 to December 2019. Analyses adapted at last French guidelines applicated corresponding of year management. RESULTS: Seventy-four non endometrioid endometrial cancer analysed in 10 centers: 34 carcinosarcoma (45,9 %), 29 serous carcinoma (39,2 %), 9 clear cells carcinoma (12,2 %) and 2 undifferentiated carcinoma (2,7 %). For initial management, endometrial cancer guidelines applicated to 45,9 %. First reason of initial guidelines « non-application ¼ was lack of surgical lymph node stadification (57,1 %). For adjuvant management, endometrial cancer guidelines applicated to 38.7 %. First reason of adjuvant guidelines « non-application ¼ was lack lymph node stadification to complete staging when it previously incompletly operated (67,6 %). DISCUSSION: Non endometrioid endometrial cancer guidelines applicability is difficult. This explicated by high age and comorbidity when surgical lymph node stadification is necessary. Using new staging technic will allow target management and better select lymph node staging indication.

Squamous cell carcinoma with sarcomatoid differentiation or carcinosarcoma of the uterine cervix associated with HPV33 infection: report of a rare case.

BACKGROUND: Squamous cell carcinoma is the most common malignant tumor of the uterine cervix with a well-documented link to infection with human papillomaviruses (HPV). According to a recent classification, there are several morphological variants of cervical squamous carcinoma, without reference to sarcomatoid squamous cell carcinoma, which is well described in other organs. CASE PRESENTATION: In this paper, we describe an extremely rare case of a 77-year-old woman with primary malignant cervical tumor displaying biphasic histomorphology with an epithelioid and sarcomatoid part; the latter was immunohistochemistry positive for cytokeratin and vimentin. The association with a high-grade squamous intraepithelial lesion and molecular proof of HPV33 infection in the tumor tissue supported our diagnosis of carcinoma with partial sarcomatoid differentiation. CONCLUSION: We report a rare case of a primary cervical epithelial tumor with a partial sarcomatoid phenotype, an unequivocal HPV infection, and an associated precancerous lesion in the cervical mucosa. This is the first description of an HPV33 infection underlying a biphasic epithelioid-sarcomatous tumor of the uterine cervix. The terminology overlap between sarcomatoid carcinoma and carcinosarcoma is also discussed.

Carcinosarcoma (adenocarcinoma, neuroendocrine carcinoma, undifferentiated carcinoma and chondrosarcoma) of the gallbladder.

We present an extremely rare case of carcinosarcoma with 4 different tumor components in an 88-year-old female. After a diagnosis of acute cholecystitis, we performed percutaneous transhepatic gallbladder drainage in the patient without success, followed by a cholecystectomy and choledocholithotomy. The mass was a 60 × 25 mm polypoid lesion of the gallbladder identified histologically as a carcinosarcoma with adenocarcinoma, neuroendocrine carcinoma, undifferentiated carcinoma and chondrosarcoma components. The biliary-type adenocarcinoma portion exhibited acinar growth patterns with columnar cells having large and markedly hyperchromatic nuclei. These tumor cells were immunohistochemically positive for MUC1 and CDX2. The neuroendocrine carcinoma, small cell type, cells were densely packed and small, with scant cytoplasm, finely granular nuclear chromatin and absence of nucleoli. The mitotic index was high. These tumor cells were immunohistochemically positive for synaptophysin, Ki-67 (index 40%), MUC1, CDX2 and c-Kit. The undifferentiated carcinoma consisted exclusively of spindle cells containing large, markedly hyperchromatic nuclei with a high mitotic index. These tumor cells were immunohistochemically positive for AE1/AE3. The chondrosarcoma was composed of blue-gray chondroid matrix and atypical chondrocytes containing large, hyperchromatic nuclei. These tumor cells were immunohistochemically positive for S100. Its attributes might be suggestive of a greater malignant potential and pathogenesis of carcinosarcoma.

A Large Carcinosarcoma of the Gallbladder Accompanied by Pancreaticobiliary Maljunction: A Case with a Six-year Survival.

Pancreatobiliary maljunction (PBM) is a rare congenital malformation, often associated with adenocarcinoma. However, PBM accompanying gallbladder carcinosarcoma has rarely been reported. A 72-year-old woman was referred to our hospital, complaining of abdominal pain. Computed tomography showed a polypoid mass in the gallbladder. Endoscopic retrograde cholangiopancreatography showed PBM, and aspirated bile demonstrated elevated levels of pancreatic-type amylase (26,780 U/L) and cancer cells. Extended cholecystectomy was performed. Histologically, the tumor had adenocarcinoma, squamous cell carcinoma and sarcoma components. Despite the large tumor size (84 mm) and intra-vessel cancer permeations, this patient has been healthy for 73 months since the surgery.

Tumor cerebral maligno epitelial-mesenquimal de probable origenneuroectodérmico sarcomatoso / Epithelial-mesenchymal malignant brain tumor of probable sarcomatous neuroectodermal origin

Objetivo: Describir el tratamiento dado y la evolución de un paciente con un tumor sarcomatosoprimario de encéfalo.Caso clínico: Se presenta una paciente de cinco años de edad, con un cuadro clínico de un mes deevolución de tortícolis y vómitos ocasionales. Al examen físico se constató papiledema bilateral enel fondo de ojo. Por tomografía computarizada se pudo diagnosticar un proceso expansivo intracranealfrontal derecho. Se realizó tratamiento quirúrgico con exéresis macroscópica total de la lesión, queanatomopatológicamente fue compatible con un meningioma fibroblástico. A los tres meses presentó recidiva tumoral, por lo que se volvió a intervenir neuroquirúrgicamente. Esta vez el diagnósticohistopatológico fue compatible con un sarcoma fibromixoide de bajo grado. Los estudios de inmunohistoquímica demostraron compatibilidad con un tumor maligno de encéfalo con patrónmixto epitelial y mesenquimal de probable origen neuroectodérmico sarcomatoso. La paciente tuvo 32 sesiones de tratamiento con radioterapia (dosis diaria de 1,8 Gy). Falleció pasados los cinco meses de la segunda cirugía.Conclusiones: El tumor maligno con patrón mixto epitelial y mesenquimal de probable origenneuroectodérmico sarcomatoso del encéfalo es una enfermedad con un comportamiento agresivo. Su localización intracraneal es excepcional. No se hallaron casos reportados en la literatura(AU)

Objective: To describe treatment and evolution of a patient with a primary sarcomatous tumor of the brain.Clinical case: A 5-year-old patient is reported with a month-long clinical condition of torticollis andoccasional vomiting. Physical examination revealed bilateral papilledema in the fundus. A right frontal intracranial expansive process was diagnosed by computed tomography. Surgical treatment was performed with total macroscopic excision of the lesion, which was anatomopathologically compatible with a fibroblastic meningioma. After three months he presented with tumor recurrence, which led to intervene neurosurgically. This time the histopathological diagnosis was compatible with a low-grade fibromyxoid sarcoma. Immunohistochemical studies showed compatibility with a malignant brain tumorwith a mixed epithelial and mesenchymal pattern of probable neuroectodermal sarcomatous origin. Thepatient had 32 sessions of radiotherapy treatment (daily dose of 1.8 Gy). This patient passed away afterfive months of the second surgery.Conclusions: The malignant tumor with mixed epithelial and mesenchymal pattern of probable neuroectodermal origin sarcomatous brain is a disease with aggressive behavior. Its intracranial locationis exceptional. No cases reported in literature were found(AU)

Identification of endometrial cancers and atypical hyperplasia: Development and validation of a simplified system for ultrasound scoring of endometrial pattern.

OBJECTIVES: To derive and validate a practical scoring system for identification of endometrial cancer (EC) or atypical hyperplasia (AH) using transvaginal ultrasonography (TVS) and gel infusion sonography (GIS) in women with postmenopausal bleeding (PMB). STUDY DESIGN: Endometrial pattern was correlated with endometrial pathology in consecutive women with PMB in both a derivation study (N = 164) and a validation study (N = 711). Logistic regression was used to derive and validate two scoring systems (A and B) for prediction of EC/AH: scoring system A was Doppler score + interrupted endo-myometrial junction (IEJ) (2 points); and scoring system B was Doppler score + IEJ (1 point) + Irregular Endometrial Outline (IESO) by GIS (1 point); the Doppler score was based on the presence of more than one single or double vessel (1 point) + multiple vessels (1 point) + large vessels (1 point). OUTCOME MEASURES: Diagnostic performance and calibration curves for identification of EC/AH. RESULTS: Both scoring systems had good observer agreement. VALIDATION DATA: Scoring was most effective with endometrial thickness (ET) ≥ 8 mm. Both scoring systems were well calibrated and performed satisfactorily in women with ET ≥ 8 mm. The sensitivity and specificity of a score of ≥ 2 points in system A were 92% and 84%; the respective values were 89% and 88% in system B. CONCLUSIONS: Scoring was highly efficient in identifying EC/AH. Four risk groups of EC/AH may guide the management of women with PMB: very low (ET < 4 mm), low (ET 4-7.9 mm), intermediate (ET ≥ 8 mm and score < 2 points) and high risk (ET ≥ 8 mm and score ≥ 2 points).

Uterine Inversion as a Result of a Large Prolapsed Carcinosarcoma of the Uterus.

BACKGROUND: Uterine inversion is most commonly seen in labour and delivery. However, it can be associated with uterine tumours, including gynaecologic malignancy. CASE: In a 66-year-old woman, uterine inversion identified at laparotomy that was found to be associated with uterine carcinosarcoma (malignant mixed mesodermal tumour) represents an unusual presentation. Surgical approach necessitated a vertical hysterotomy to amputate and deliver the uterine tumour. CONCLUSION: Uterine inversion in gynaecologic oncology may be associated with sarcoma or malignant mixed mesodermal tumour. This can represent a diagnostic and surgical challenge and should be considered.

[Carcinosarcoma of the Esophagus That Presented as Esophageal Stenosis].

Esophageal carcinosarcoma is a rare malignant tumor. A 76-year-old man consulted near hospital about dysphagia. A gastrointestinal fiberscopy showed a stricture of the thoracic esophagus at approximately 34 cm from the incisor, and the macroscopic type of the tumor was 0-Ip. Biopsy results indicated carcinosarcoma. The patient underwent esophagectomy and regional lymphadenectomy with gastric tube reconstruction by laparoscopy-assisted surgery and thoracotomy. Pathological examination of the surgical specimen revealed that the majority of the tumor was composed of spindle-shaped atypical cells, but because a very small transitional area between squamous cell carcinoma and sarcoma was noted, a diagnosis of carcinosarcoma was made. The depth of invasion was small, and no region lymph node metastasis was detected. We classified the tumor as pT1b(SM)N0M0, pStage I. Immunohistochemically, the spindle-shaped sarcomatous cells displayed a posi- tive reaction to vimentin and cytokeratin AE1/AE3. Ki -67(MIB-1)labeling index was high. The patient was discharged after an uneventful postoperative course and remains well as an outpatient at his 6-month follow-up. We report this case with a review of the literature.