Small Cell Neuroendocrine Carcinoma of the Vulva: Case Report and Literature Review

Background: Neuroendocrine neoplasms are those that develop from a neuroendocrine cell. They most commonly affect the lungs, gastrointestinal tract, and pancreas, being rare conditions in the female genital tract. When present, these neoplasms often manifest with nonspecific signs and symptoms such as pain, itching, swelling, single-focus lesions, bleeding, and enlargement of inguinal lymph nodes, in addition to the presence of progressively enlarging vulvar nodules. Consequently, the diagnostic investigation involves histopathological examination and confirmation through immunohistochemistry. Objective: To present a comprehensive understanding of this rarely studied pathology. The primary objective is to provide valuable insights that could aid in the future development of universally applicable treatment guidelines. Case Presentation: A 57-year-old female, with no prior comorbidities, menopause at 36, who presented with a left vulvar nodule accompanied by intense pain and swelling, later diagnosed with small cell neuroendocrine carcinoma in the vulva. Conclusion: This case report highlights the importance of enhancing our knowledge regarding small cell neuroendocrine carcinoma in the vulva, given its scarcity in medical literature. The information presented here underscores the need for standardized diagnostic and treatment approaches, paving the way for future consensus on managing this uncommon but challenging neoplasm.

Endoscopic diagnosis of early-stage primary esophageal small cell carcinoma: Report of two cases

BACKGROUND Primary esophageal small cell carcinoma(PESCC)is a highly aggressive malignancy,and its detailed clinical behaviors have remained virtually unknown.Because of the rapid tumor progression,the diagnosis of esophageal small cell carcinoma at early stage is extremely difficult in clinical practice.Currently,only a handful of PESCC cases have been reported.CASE SUMMARY Case 1:A 62-year-old man was diagnosed with an esophageal submucosal tumor by endoscopy.Endoscopic ultrasonography showed a 0.8 cm low echo nodule in the muscularis mucosa.As the patient refused to undergo endoscopic resection,neoplasia was detected by endoscopy 1 year later.Case 2:A 68-year-old woman was diagnosed as having an esophageal submucosal tumor by endoscopy at a local hospital.About 2 wk later,we performed endoscopic ultrasonography and found a 1 cm low echo nodule in the muscularis mucosa;the submucosal was thinner than normal but still continuous;mucosal hyperemia and erosion were found on the surface of the tumor.Endoscopic submucosal dissection(ESD)was performed and the histopathological finding showed a small cell carcinoma invading the submucosal layer.CONCLUSION Early esophageal small cell carcinoma shows submucosal infiltrating growth with a hypoechoic mass in the muscularis mucosa as diagnosed by endoscopic ultrasonography.It is easily misdiagnosed as submucosal masses.Endoscopic manifestations should be identified and pathological biopsies should beemployed. ESD may be performed to provide an opportunity for early treatmentof PESCC.

SURGICAL TREATMENT OF PRIMARY ESOPHAGEAL SMALLCELL CARCINOMA

Objective: To study the clinical biocharacteristics of primary esophageal small-cell carcinoma (PESC) and factors influencing prognosis and to find rational indications for combination therapy. Methods: To analyze the clinical materials of 47 patients who had undergone an operation with PESC and to compare it with those patients with esophageal squamous-cell carcinoma (ESCC) or primary esophageal adenocarcinoma (PEAC). Results: The overall resectability, morbidity and 30-day mortality rates of PESC were 93.6%, 17.0% and 2.1% respectively, similar to those of ESCC or PEAC. TNM staging and lymph node metastasis were the major determinants influencing long-term survival. Tumor length, depth of tumor invasion and type of operation had little influence on long-term prognosis. The 5-year survival rate of PESC was 7.5%, which was much lower than that of ESCC and PEAC (P<0.01). Among the 42 deceased patents, one died of anastomotic leakage and the others died of remote metastasis and recurrence. Adjuvant chemotherapy did not help improve the patients’ long-term survival. Conclusions: Compared with ESCC and PEAC, PESC is the most malignant type with early lymphatic and hematogenous metastases and poor prognosis. Lymph node metastasis is the major factor influencing the prognosis. Patients in stage 0, I and II a of PESC are indicated for surgical resection, while those in stage II b, III or IV should be managed with non-surgical combined therapy.

Primary small cell esophageal carcinoma,chemotherapy sequential immunotherapy:A case report

BACKGROUND Primary small cell esophageal carcinoma(PSCEC)is aggressive and rare,with a worse prognosis than other subtypes esophageal carcinoma.No definitive and optimum standard guidelines are established for treating it.Herein,we report a case of PSCEC,including a current literature review of PSCEC.CASE SUMMARY A 79-year-old male was diagnosed PSCEC with multiple lymph node metastasis thorough computed tomography,positron emission tomography-computed tomography,endoscopy and pathology.Surgery was not suitable for this patient.He was treated with etoposide 100 mg/m2 and cisplatin 25 mg/m2 on days 1-3,every 3 wk for 4 cycles.The tumor and lymph nodes became smaller and dysphagia and vomiting symptoms improved.The patient could not tolerate subsequent chemotherapy(CT)because of hematological toxicity;therefore,we performed immunotherapy(durvalumab,1500 mg)every 4 wk.At present the patient has received 12 cycles immunotherapy over about 1 year.He is still receiving treatment and follow-up.CONCLUSION PSCEC with multiple lymph nodes metastasis does not always indicate surgery.CT may extend survival time and improve the quality of life in the absence of surgery.Immunotherapy or immunotherapy plus CT may also work as a treatment for PSCEC.

Primary small cell neuroendocrine carcinoma of the right posterior tongue

Small cell neuroendocrine carcinoma(SNEC)is an extremely aggressive tumor and mainly occurs in the lung.Primary extra-pulmonary SNEC is rare.To date,only 11 primary SNECs occurring in the oral cavity have been reported in the English literature.We describe a case of primary SNEC of the right posterior tongue in a 46-year-old man.The patient had stage IVA disease and received adjuvant chemotherapy,followed by radical surgery and radiotherapy.He remained tumor-free for 20 mo before death due to gastrointestinal metastasis.The relevant literature on the 11 previously reported patients was reviewed,and the clinical features,histopathological characteristics,differential diagnosis and therapeutic strategies of this rare tumor were analyzed.

Cetuximab combined with chemotherapy for simultaneous esophageal squamous cell carcinoma and colon adenocarcinoma:A case report

BACKGROUND Multiple primary carcinomas(MPCs)are defined as two or more independent primary cancers that occur simultaneously or sequentially in the same individual.Synchronous MPCs are rarer than solitary cancers or metachronous MPCs.Accurate diagnoses of synchronous MPCs and the choice of treatment are critical for successful outcomes in these cases.CASE SUMMARY A 64-year-old patient presented with dysphagia,without obvious cause.A diagnosis of synchronous esophageal squamous cell carcinoma and colon adenocarcinoma with liver metastasis was confirmed based on examination and laboratory results.After multi-disciplinary consultations,combination chemotherapy(a 3-wk cycle with oxaliplatin 212 mg administered on day 1 and capecitabine 1.5 g twice daily on days 1-14)and esophageal cancer radiotherapy were initiated.Based on the results of genetic testing,we switched to a regimen of leucovorin+fluorouracil+oxaliplatin and cetuximab regimen for 8 cycles.Subsequently,capecitabine and bevacizumab were administered until the most recent follow-up,at which the tumor remained stable.CONCLUSION Successful cetuximab chemotherapy treatment provides a reference for the nonoperative and homogeneous treatment of different pathological types of synchronous MCPs.

Coexistence of small cell neuroendocrine carcinoma and villous adenoma in the ampulla of Vater

Small cell neuroendocrine carcinoma of the ampulla of Vater is extremely rare and different from the common ampullary adenocarcinoma. The ampullary adenoma is also a rare neoplasm and has the potential to develop an adenocarcinoma. Their coexistence has been rarely reported in the literature. We herein describe an unusual case of a small cell neuroendocrine carcinoma associated with a villous adenoma in the ampulla of Vater with emphasis on computed tomography (CT) and histopathological findings. We also discuss their clinical, histopathological and radiological features as well as possible histogenesis.

Development and validation of a prognostic nomogram model for Chinese patients with primary small cell carcinoma of the esophagus

BACKGROUND Primary small cell carcinoma of the esophagus(PSCE)is a highly invasive malignant tumor with a poor prognosis compared with esophageal squamous cell carcinoma.Due to the limited samples size and the short follow-up time,there are few reports on elucidating the prognosis of PSCE,especially on the establishment and validation of a survival prediction nomogram model covering general information,pathological factors and specific biological proteins of PSCE patients.AIM To establish an effective nomogram to predict the overall survival(OS)probability for PSCE patients in China.METHODS The nomogram was based on a retrospective study of 256 PSCE patients.Univariate analysis and multivariate Cox proportional hazards regression analysis were used to examine the prognostic factors associated with PSCE,and establish the model for predicting 1-,3-,and 5-year OS based on the Akaike information criterion.Discrimination and validation were assessed by the concordance index(C-index)and calibration curve and decision curve analysis(DCA).Histology type,age,tumor invasion depth,lymph node invasion,detectable metastasis,chromogranin A,and neuronal cell adhesion molecule 56 were integrated into the model.RESULTS The C-index was prognostically superior to the 7th tumor node metastasis(TNM)staging in the primary cohort[0.659(95%CI:0.607-0.712)vs 0.591(95%CI:0.517-0.666),P=0.033]and in the validation cohort[0.700(95%CI:0.622-0.778)vs 0.605(95%CI:0.490-0.721),P=0.041].Good calibration curves were observed for the prediction probabilities of 1-,3-,and 5-year OS in both cohorts.DCA analysis showed that our nomogram model had a higher overall net benefit compared to the 7th TNM staging.CONCLUSION Our nomogram can be used to predict the survival probability of PSCE patients,which can help clinicians to make individualized survival predictions.

A case report of primary small cell carcinoma of the breast and review of the literature

Primary small cell carcinoma (SCC) of the breast, an exceedingly rare and aggressive tumor, is often characterized by rapid progression and poor prognosis. We report a case of primary SCC of the breast that was diagnosed through pathologic and immunohistochemical examinations. Computed tomography (CT) scans failed to reveal a non-mammary primary site. Due to the scant number of relevant case summaries, this type of tumor is proved to be a diagnostic and therapeutic challenge. Therefore, we also reviewed relevant literature to share expertise in diagnosis, clinicopathologic characteristics, treatment, and prognosis of this type of tumor. Future studies with more cases are required to define more appropriate treatment indications for this disease.

Small-cell neuroendocrine carcinoma of the prostate： are heterotransplants a better experimental model？

Small-cell neuroendocrine carcinoma of the prostate （SCNCP） is an uncommon type of prostate cancer. However, it is of clinical importance because it is one of the most aggressive tumors of the prostate with a very poor prognosis. There exist few artificially cultured tumor cell lines to study SCNCE Then, another approach to that study consists in the use of fresh tumor tissue obtained from patients and its heterotransplantation into host mice. The purpose of this review is to integrate data from more than 20 years of heterotransplantation research in the study of small-cell neuroendocrine carcinoma of the prostate （SCNCP）. Heterotransplantation has provided data regarding the histopathology, karyotype, DNA content, cell cycle frequency, tumor markers, androgen receptor expression, metastasis and take rate of this prostate disease. When possible, comparisons between original in situ specimens removed from patients and heterotransplanted tissue from host mice have been made. There are advantages, as well as limitations, that have been identified for SCNCP heterotransplants versus xenotransplantation of cultured cells. Overall, heterotransplanted tumors are better than conventional tumor xenografts at retaining tumor morphology, pathology, secretory activity and expression of tumor markers of the patient＇s original specimen. Furthermore, heterotransplanted tissue preserves the three-dimensional tumor architecture of the prostate to maintain critical stromal-epithelial cell interactions.

Advance in the Studies on Small Cell Neuroendocrine Carcinoma of the Paranasal Sinuses

Small cell neuroendocrine carcinoma (SCNEC) of the paranasal sinuses is extremely rare,with an unclear pathogenesis.The presence of neuroendocrine granules is suggestive of neuroendocrine differentiation.It was reported that this disease relates to the presence of accessory salivary glands,and some basic research has shown that it might originate from the multi-potent stem cells.There are no specific clinical symptoms but rhinal and ophthalmological symptoms are found in most cases.Diagnosis mainly depends on histopathological manifestations,immunohistochemical results and features of the electron microscopic ultra-structure.Pathological differentiation from poorly differentiated squamous carcinoma,melanoma,esthesioneuroblastoma and neuroglioma etc.is needed.No unified regimen has been employed in treating the disease.At present,combined therapy has a manifest therapeutic effect,such as success with the 2003 French regimen.Tumor relapse is common and prognosis is poor.A complete combined treatment plan will be helpful to improve the prognosis.

Primary Ovarian Small Cell Carcinoma of Pulmonary Type: Analysis of 6 Cases and Review of 31 Cases in the Literatures

Objective Primary ovarian small cell carcinoma of pulmonary type(SCCOPT)is a rare ovarian tumor with a poor prognosis.The platinum-based chemotherapy is the standard treatment.However,there is little research on the clinical characteristics of SCCOPT and the potential benefits of other treatments due to its low incidence.The study aims to investigate clinicopathological characteristics and treatment of SCCOPT.Methods We summarized the clinical,imaging,laboratorical and pathological characteristics of 37 SCCOPT cases,in which 6 cases were admitted to the Gansu Provincial Hospital from the year of 2008 to 2022 and 31 cases reported in 17 English and 3 Chinese literatures.Results The median age of the studied SCCOPT cases(n=37)was 56.00(range,22-80)years.Almost 80%of them had a stageⅢorⅣtumor.All patients underwent an operation and postoperative chemotherapy.Nevertheless,all cases had a poor prognosis,with a median overall survival time of 12 months.Immunohistochemical y,the SCCOPT of all patients showed positive expressions of epithelial markers,such as CD56 and sex-determining region of Y chromosome-related high-mobility-group box 2(SOX-2),and negative expressions of estrogen receptor,progesterone receptor,vimentin,Leu-7,and somatostatin receptor 2.The tumor of above 80%cases expressed synaptophysin.Only a few cases expressed neuron-specific enolase,chromogranin A,and thyroid transcription factor-1.Conclusions SCCOPT had a poor prognosis.SOX-2 could be a biomarker to be used to diagnose SCCOPT.

Early Age of Onset, Multiple Primary Malignancies and Poor Prognosis Are Indicative of an Inherited Predisposition to Esophageal Squamous Cell Carcinoma in Familial Rather Than Sporadic Disease- An Update Based on 14- to 23-year Follow-up

OBJECTIVE To demonstrate the effects of an inherited predisposition to familial esophageal squamous cell carcinoma （ESCC） through the comparison and analysis of the clinicopathologic differences between familial and sporadic ESCC cases. METHODS Differences in age of onset, prevalence rates of double primary ESCC, and survival rates between familial ESCC （n = 476） and sporadic ESCC cases （n = 1226） were analyzed. RESULTS Overall, familial ESCC cases showed a significantly younger age of onset （51.9±8.2 vs. 53.4 ±8.0, Pt.test = 0.00）, a significantly higher prevalence rate for double ESCC （2.73 % vs. 1.22%, adjusted with TNM：χMH2 = 4.029, P = 0.045）, and a lower survival rate than in sporadic cases （Pwald = 0.04）. The familial cases showed both a younger age of onset and poorer survival in most subgroups, and the differences were more marked in early-stage rather than in the .late-stage disease groups. CONCLUSION Theses findings confirm the existence of familial as opposed to sporadic ESCC. By the theory of the ＂two-hit＂ origin of cancer, these findings also suggest that the ＂first hit＂, a genetic predisposition, can affect the age of onset, number of primary carcinomas, and the prognosis for familial ESCC patients.

Diagnosis and treatment of primary small cell carcinoma of urinary bladder

Objective To investigate clinical and pathological features of small cell carcinoma of urinary bladder. Methods The pathological and clinical data of 9 cases of small cell carcinoma were analyzed retrospectively.

Small cell carcinoma of the liver and biliary tract without jaundice

An 80-year-old woman presenting with chest pain was found to have a large,lobulated soft tissue mass in the liver and nearby tissues on abdominal computed tomography(CT).The tumor had invaded the common hepatic artery and main portal vein.Jaundice developed 4 wk later,at which point,a pancreas and biliary CT scan revealed a large mass in the right lobe of the liver and a hilar duct obstruction,which was found to be a small cell carcinoma.Despite its rarity,liver and bile duct small cell carcinoma should be considered in the differential diagnosis of atypical chest pain without jaundice.

Small-cell carcinoma of the prostate with negative CD56,NSE,Syn,and CgA indicators:A case report

BACKGROUND Small-cell carcinoma of the prostate(SCCP)is a clinically rare malignant tumor,accounting for<1%of all prostate tumors.However,negativity for all SCCP neuroendocrine markers is rare.Herein,we report a case of SCCP with completely negative neuroendocrine markers and explore its clinicopathologic features,thus improving the understanding of its clinical diagnosis and management.CASE SUMMARY We report the case of a 48-year-old patient with SCCP negative for common sensitive neuroendocrine-staining indicators.Dysuria was the first symptom,and rectal examination revealed a hard prostate,palpable nodules,diffuse prostate enlargement,no pressure pain,no blood staining in the finger sleeve,1.33 ng/mL total prostate-specific antigen level,and a free-to-total prostate-specific antigen ratio of 0.21 ng/mL.Ultrasound suggested a prostate size of 5.3 cm×5.8 cm×5.6 cm,and magnetic resonance imaging suggested prostate cancer.The lower posterior bladder wall,rectal mesentery,and bilateral seminal vesicles were invaded,with multiple lymph node metastases in the pelvis.A whole-body bone scan suggested an abnormally active multiple bone metabolism and possible bone metastases.Head and lungs computed tomography revealed no significant nodal shadow.Following a pathological diagnosis of SCCP after a prostate puncture,with negative indicators of common sensitive neuroendocrine staining,chemotherapy was administered;the patient died 4-5 mo after SCCP diagnosis.CONCLUSION SCCP is a rare disease characterized by atypical clinical symptoms,limited treatment options,a short survival period,and a poor prognosis.

Progress in Diagnosis and Treatment of Small Cell Carcinoma of the Cervix

Small cell carcinoma of the cervix （SCCC） belongs to the neuroendocrine carcinomas, and it is a rare gynecological tumor of high-potential malignancy. It has a poorer prognosis compared to cervical squamous cancer or adenocarcinoma, and the therapeutic regimen of the disease differs. Diagnosis is based on pathomorphological characteristics, i.e., the small and round cancer cells （oat cell） which are uniform in shape and size, with the immunohistochemical marker helpful for diagnosis. Combined therapy is first recommended, Postoperative chemotherapy with platinum/etoposide （PE）, vincristine/adriamycin/cyclophosphamide （VAC） and taxel/carboplatin （TP） can markedly improve the prognosis of early SCCC patients.

Prostatic Small Cell Carcinoma: Diagnosis and Management

Prostatic small cell carcinoma (PSCC) is a distinct clinical phenotype of prostate cancer. Although rare, this phenotype is highly aggressive with very high mortality. Due to this, it is imperative for clinicians to be aware of it, diagnose it early and treat it appropriately. In this article we discuss the current literature, outline a plan for its diagnosis and management, and highlight latest research on this topic.

Neuroendocrine carcinoma of the extrahepatic bile duct: Case report and literature review

Neuroendocrine carcinoma (NEC) of the extrahepatic bile duct is rare, and only 22 cases have been reported. Only two of these were large-cell NEC (LCNEC); the vast majority were small-cell NEC. Here, we report a third case of LCNEC of the extrahepatic bile duct. A 76-year-old male presented to a local hospital with painless jaundice. Imaging studies revealed a tumor at the hepatic hilum. The patient underwent right hepatic lobectomy, bile duct resection, and cholecystectomy. The resection specimen showed a 5.0-cm invasive neoplasm involving the hilar bile ducts and surrounding soft tissue. Histologically, the tumor consisted of nests of medium to large cells with little intervening stroma. The tumor invaded a large portal vein branch. All four excised lymph nodes were positive for metastasis, and metastatic deposits were also present in the gallbladder wall. The tumor was diffusely positive for synaptophysin and focally positive for chromogranin A. Approximately 70%-80% of the tumor cells were positive for Ki-67, indicating strong proliferative activity. A diagnosis of LCNEC was made. A few bile ducts within and adjacent to the invasive tumor showed dysplasia of the intestinal phenotype and were focally positive for synaptophysin and chromogranin A, suggesting that the dysplastic intestinal-type epithelium played a precursor role in this case. A postoperative computer tomography scan revealed rapid enlargement of the abdominal and retroperitoneal lymph nodes. The patient died 21 d after the operation. NEC of the bile duct is an aggressive neoplasm, and its biological characteristics remain to be better defined.

Neuroendocrine carcinomas arising in ulcerative colitis:Coincidences or possible correlations?

Patients with inflammatory bowel disease （IBD） are at increased risk of colorectal malignancies. Adenocarcinoma is the commonest type of colorectal neoplasm associated with ulcerative colitis （UC） and Crohn＇s disease, but other types of epithelial and non-epithelial tumors have also been described in inflamed bowel. With regards to non-epithelial malignancies, lymphomas and sarcomas represent the largest group of tumors reported in association with IBD, especially in immunosuppressed patients. Carcinoids and in particular neuroendocrine neoplasms other than carcinoids （NENs） are rare tumors and are infrequently described in the setting of IBD. Thus, this association requires further investigation. We report two cases of neoplasms arising in mild left-sided UC with immuno- histochemical staining for neuroendocrine markers： a large cell and a small cell neuroendocrine carcinoma of the rectum. The two patients were different in age （35 years vs 77 years） and disease duration （11 years vs 27 years）, and both had never received immunosuppressant drugs. Although the patients underwent regular endoscopic and histological follow-up, the two neoplasms were locally advanced at diagnosis. One of the two patients developed multiple liver metastases and died 15 mo after diagnosis. These findings confirm the aggressiveness and the poor prognosis of NENs compared to colorectal adenocarcinoma. While carcinoids seem to be coincidentally associated with IBD, NENs may also arise in this setting. In fact, long-standing inflammation could be directly responsible for the development of pancellular dysplasia involving epithelial, goblet, Paneth and neuroendocrine cells. It has yet to be established which IBD patients have a higher risk of developing NENs.