Combined immune checkpoint inhibitors of CTLA4 and PD-1 for hepatic melanoma of unknown primary origin: A case report

BACKGROUND Melanoma is uncommonly found in lymph nodes,subcutaneous tissue,or visceral organs without a primary lesion,where it is identified as metastatic melanoma with unknown primary(MUP).Hepatic MUP is extremely rare and has a poor prognosis.There is limited information on its pathogenesis,clinical and imaging features,and pathological findings.There are no guidelines for the use of immune checkpoint inhibitors(ICIs)in hepatic MUP,and the treatment outcome has rarely been reported.CASE SUMMARY A 42-year-old woman presented to our hospital with hepatic tumors found incidentally during a routine check-up.Contrast-enhanced abdominal computerized tomography showed multiple mass lesions in the liver.Pathological results revealed melanoma,which was confirmed by immunohistochemical staining for HMB-45(+),Melan-A(+),S-100(+),and SOX10(+).There was no evidence of primary cutaneous,ocular,gastrointestinal,or anal lesion on a comprehensive examination.The patient was diagnosed with hepatic MUP.She received combined antibodies against cytotoxic T-lymphocyte-associated antigen 4(CTLA-4,ipilimumab)and programmed death protein-1(PD-1,nivolumab).She died of hepatic failure 9 mo after hepatic MUP was diagnosed.This the first case of hepatic MUP treated with combined ipilimumab and nivolumab,who showed better outcome than previous cases.CONCLUSIONCombined ICIs of PD-1 and CTLA-4 may be considered as the first-line therapyfor patients with hepatic MUP.

Perioperative mortality of metastatic spinal disease with unknown primary: A case report and review of literature

BACKGROUND Spinal metastases are common in patients with malignancies,but studies on those metastasized from unknown primaries are scarce due to the difficulty in treatment and the relatively poor prognosis.Knowledge of surgical complications,particularly perioperative mortality,in patients with spinal metastases from unidentified sources is still insufficient.CASE SUMMARY A 54-year-old man with chest-back pain was diagnosed with spinal metastasis in the seventh thoracic vertebra(T7).Radiographic examinations,as well as needle biopsy and immunohistochemical tests were performed to verify the characteristics of the lesion,resulting in an inconclusive diagnosis of poorly differentiated cancer from an unknown primary lesion.Therefore,spinal surgery was performed using the posterior approach to relieve symptoms and verify the diagnosis.Postoperative histologic examination indicated that this poorly differentiated metastatic cancer was possibly sarcomatoid carcinoma.As the patient experienced unexpectedly fast progression of the disease and died 16 d after surgery,the origin of this metastasis was undetermined.We discuss this case with respect to reported perioperative mortality in similar cases.CONCLUSION A comprehensive assessment prior to surgical decision-making is essential to reduce perioperative mortality risk in patients with spinal metastases from an unknown origin.

Comparison between Metastatic Spinal Tumour of Unknown Primary Tumour with a Known Primary

Patients presented with spinal metastases from unknown primary tumours are rare. In this research we evaluated all patients with metastatic spinal tumour of unknown primary tumour, all patients were evaluated pre-operatively and comparison was done to those patients who had known primary tumour the study aimed to compare the group with known primary and the group with the unknown primary regarding the: mean age, gender, duration of symptoms, complication rate, region of the spine affected by metastasis, presence or absence of other skeletal or visceral metastasis, histological cell type and neurological outcome. Method: A retrospective study was performed on 40 patients presented to Neuroscience hospital in Baghdad from January 2010 till January 2014;all patients with metastatic spinal tumour were included in our study. We reviewed all patients’ records including age, sex, primary tumour, duration of their symptoms, neurological out come and complications. Results: Out of the 40 patient who presented with spinal tumours that underwent surgery duo to metastatic spinal tumour, five patients presented with spinal compression duo to metastatic tumour of unknown primary tumour (12.5%). The mean age was 64 years, 4 male and one female. For those with a known primary tumour mean age was 61 year, 22 male 13 female. Duration of symptoms prior to surgery was the same 180 days for those with unknown primary and 190 day for those with known primary tumours. They also had similar neurological outcome (80%) remain the same or improved post operatively for those with unknown primary and (85.7%) for those with a known primary tumour, and a similar complication rate for unknown primary was 25% versus 28% for known. The primary site of metastatic spinal tumour of unknown primary was confirmed after histopathology all shown adenocarcinoma four from the lung (80%) and one from colorectal. While the most common known carcinoma site were the lung 18 patient (51.4%), colorectal 8 (22.8%), breast 7 (20%), and renal 2 (5.71%). All patient who complain from secondary spinal metastasis with unknown primary tumour didn’t show any other skeletal or visceral metastasis, while those with a known primary tumour 6 patient out of 35 (17.1%) shown involvement of other site, the indication of surgery was to remove cord compression and restore neurological deficit. The most common site for metastasis was the dorsal spine for those of an unknown primary tumour 4 out of 5 patients (80%), and for those of a known primary tumour it was the lumbar area 28 out of 35 patient (80%). In conclusion metastatic spinal tumour of unknown primary was a common condition;it has similar demographic features, complications, and neurologic sequel with the spinal metastasis of known primary. Adenocarcinoma of the lung is the most common primary tumour proved after histopathology for spinal metastasis of unknown primary.

Clinical applications of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography in carcinoma of unknown primary

Background Carcinoma of unknown primary （CUP） encompasses a heterogeneous group of tumors with varying clinical features. The management of patients of CUP remains a clinical challenge. The purpose of this study was to evaluate the clinical applications of integrated 18F-fluorodeoxyglucose positron emission tomography/computed tomography （FDG PET/CT） information in patients with CUP, including detecting the occult primary tumor and effecting on disease therapy.

Metastatic inguinal lymph nodes with two different histological types in a case of carcinoma of unknown primary site

Cancer of unknown primary site is a group of uncommon cancers where patients present with metastatic disease and the primary site is not identifi ed,even after a complete workup to establish the diagnosis.Inguinal metastasis with unknown primary is even more uncommon,and histological type is the most important guiding factor to look for the primary.This report describes the rare situation of inguinal metastasis with an unknown primary site where a combination of squamous and transitional cell carcinoma was found on fi nal histopathology.It highlights the importance of multimodality approach including an aggressive surgical resection combined with adjuvant radiation therapy to achieve an optimal outcome.

Primary ascending colon cancer accompanying skip metastases in left shoulder skin and left neck lymph node: A case report

BACKGROUND Lymph node skip metastases are common in lung,breast,and thyroid cancer patients,but are rare in colon cancer patients.Specifically,lymph node skip metastases occur in 1%-3%of colon cancer patients.Previous reports have demonstrated colon cancer skip metastases involving the retropancreatic and portocaval lymph nodes and Virchow's node;however,reports involving skip metastases into the left neck lymph nodes and left shoulder skin are extremely rare,as are related reports of clinical treatment and prognosis.CASE SUMMARY A 44-year-old Chinese man was admitted to the hospital for evaluation of persistent shoulder pain for 3 d and a cutaneous mass(3.0 cm×2.0 cm)on the left shoulder.The left shoulder cutaneous mass was excised and bisected,revealing tissues with a fish-like appearance.The pathologic diagnosis of the cutaneous mass suggested a signature[CDX-2(++),CK20(++),Ki-67(+)>50%]of infiltrating or metastatic colorectal adenocarcinoma.An enhanced computed tomography scan of the abdomen revealed chronic appendicitis with fecal stone formation,cecal edema,and a pelvic effusion.A colonoscopy revealed a cauliflower-like mass within the ascending colon area that involved the lumen.The surface of the ascending colon mass was eroded and bleeding;a biopsy was performed.The pathologic diagnosis of the colonoscopy biopsy was an ascending colon mucinous adenocarcinoma.The patient underwent a laparoscopic radical resection of the right colon based on the pathological diagnosis.The tumor was 5.0 cm×4.5 cm×1.8 cm in size and infiltrated the entire thickness of the intestinal wall with vascular tumor thrombi.No nerve tissue involvement was noted.The ileum and colon resection margins were negative.The postoperative pathologic analysis revealed non-metastatic involvement of ileocecal,pericolic,or peri-ileal lymph nodes.The postoperative medical examination revealed palpably enlarged lymph nodes in the left neck,and the following color Doppler ultrasound examination of the neck confirmed enlarged lymph nodes in the left neck.After surgical resection and pathologic diagnosis,a common pathologic signature consistent with resected cutaneous mass and right colon was identified,suggesting skip metastasis of left cervical lymph nodes.The patient was then treated with eight courses of chemotherapy and under followup evaluations for 4 years;currently,no tumor recurrences or metastases have been noted.CONCLUSION We report an abnormal skip metastasis involving the left shoulder skin and left neck lymph node in a patient with ascending colon adenocarcinoma.Specifically,we observed non-metastatic involvement of the lymph nodes around the tumor site but with metastases to the cervical lymph nodes.The standard surgical operations were performed to resect the cutaneous mass,tumor tissue,and cervical lymph nodes,followed by chemotherapy for eight courses.The patient is healthy with no tumor recurrences or metastases for 4 years.This clinical case will contribute to future research about the abnormal skip metastasis in colon cancers and a better clinical treatment design.

Long-term survivor of metastatic squamous-cell head and neck carcinoma with occult primary after cetuximab-based chemotherapy:A case report

BACKGROUND Cancer of unknown primary(CUP)is a histological proven malignant tumor whose origin cannot be detected despite careful examination.Most cervical lymph node metastases in CUP(80%)will originate from head and neck sites,and 15%show infiltration of squamous carcinoma cells.The survival rates of CUP are poor:The 5-year-survival rate ranges from 10%to 15%.First-line treatment recommendation for advanced,inoperable squamous cell carcinoma of head/neck(HNSCC)was cetuximab plus platinum-fluorouracil chemotherapy until recently,when checkpoint inhibitors proved clinically beneficial therapies.CASE SUMMARY Here,we report a case of a 42-year-old female patient with cervical and abdominal lymph node and distant bone metastases of an occult primary of the head and neck(squamous cell carcinoma,human papillomavirus positive).The cancer was diagnosed during pregnancy 10 years ago,and after giving birth,the patient was treated with cetuximab plus platinum-fluorouracil chemotherapy achieving complete remission(CR).CR lasted 26 mo when new metastases(abdominal lymph node,lumbar vertebral body)emerged.Both manifestations were irradiated.From then on,the patient has not received any further treatment,and her disease has remained controlled.Ten years after the initial cancer diagnosis,the patient is still alive and in good health,representing an exceptional case of HNSCC.CONCLUSION This case illustrates the exceptional clinical course and benefits of combined therapy approaches in advanced metastatic HNSCC with occult primary.

Positron-emission tomography/computed tomography imaging in head and neck oncology:An update

Cancers of the head and neck account for more than half a million cases worldwide annually, with a significant majority diagnosed as squamous cell carcinoma(HNSCC). Imaging studies such as contrast-enhanced computed tomography(CT), magnetic resonance imaging(MRI) and ^(18)F-2-fluoro-2-deoxy-D-glucose positron-emission tomography/computed tomography(^(18)F-FDG PET/CT) are widely used to determine the presence and extent of tumors and metastatic disease, both before and after treatment. Advances in PET/CT imaging have allowed it to emerge as a superior imaging modality compared to both CT and MRI, especially in detection of carcinoma of unknown primary, cervical lymph node metastasis, distant metastasis, residual/recurrent cancer and second primary tumors, often leading to alteration in management. PET/CT biomarker may further provide an overall assessment of tumor aggressiveness with prognostic implications. As new developments emerged leading to better understanding and use of PET/CT in head and neck oncology, the aim of this article is to review the roles of PET/CT in both pre- and post-treatment management of HNSCC and PET-derived parameters as prognostic indicators.

Malignant Peripheral Nerve Sheath Tumor of the Thigh Invading the Superficial Femoral Artery, with Necrotic Lung Metastases as Presenting Symptoms

A NF1 (neurofibromatosis 1) patient developed multiple necrotic lung metastases from a sciatic malignant peripheral nerve sheath tumor (MPNST) invading the superficial femoral artery. The first diagnosis was metastases of a non-small-cell adenocarcinoma because the right calf MPNST was not clinically noticeable ant that the chest/abdomen PET/CT did not include the region of the legs. When the MPNST was diagnosed, new histological analysis on the metastases changed the diagnosis to that of epithelioid undifferentiated sarcoma. The article deals with the sometimes-delayed diagnosis in those NF1 patients with large palpable masses and chronic pain pre-existing the malignant transformation, and discusses the difficulty of the biopsy of necrotic metastases.