title: Leukemoid reaction, bone marrow invasion, fever of unknown origin, and metastatic pattern in the natural history of advanced undifferentiated carcinoma of nasopharyngeal type: a review of 255 consecutive cases.
abstract: OBJECTIVE
  This study is an analysis of frequency and relationship regarding two undifferentiated carcinoma of nasopharyngeal type (UCNT)-associated paraneoplastic syndromes (PNS): leukemoid reaction (LR) and fever of unknown origin (FUO) with bone marrow invasion (BMI) and metastatic pattern.
  
  
  METHODS
  A consecutive UCNT patient cohort (N = 255) with locally advanced (n = 142) or metastatic (n = 113) disease receiving chemotherapy alone or in combination with radiotherapy was studied. All patients had a complete baseline work-up that included bone marrow biopsy.
  
  
  RESULTS
  UCNT has distinctive features among head and neck squamous cell cancers (HNSCC). These include early subclinical dissemination, with 70% of metastases appearing within 18 months of first symptoms. Metastases are common in bone (65% v 25% in HNSCC), liver (29% v 23%), and lung (18% v 84%), and BMI is observed in 25% of UCNT patients with metastases. Metastases likelihood is related to lymph node involvement, with 64% of patients with metastases having N3 disease. Involved lymph nodes in contrasted CT scans revealed hypodensity in 26% of UCNT patients versus 79% in patients with other HNSCC. Hypercalcemia was observed in one case. LR was identified in 41 patients (16%); in 26 of the 41 patients (64%) it was observed concomitant with N3 and/or metastatic disease. FUO was found in 23 patients (9%) and was associated in four instances with BMI and in 17 with LR (in four instances with both). Brain metastases or meningeal carcinomatosis were not observed despite the high rate of skull base compromise. Paraneoplastic signs were observed in 47 of 255 cases (18.5%) and were more frequent in patients with metastases. However, PNS were observed in 15 patients with negative metastases work-up.
  
  
  CONCLUSIONS
  The PNS described could help in the diagnosis and follow-up of UCNT patients because they may be the first manifestation of the disease or may reappear with relapse. BMI is a frequent finding in patients with metastases and is unrelated to PNS.
authors.affiliation: Department of Medicine, Institute Gustave Roussy, Savigny le Temple, France.
authors.forename: E
authors.initials: E
authors.lastname: Cvitkovic
authors.forename: M
authors.initials: M
authors.lastname: Bachouchi
authors.forename: H
authors.initials: H
authors.lastname: Boussen
authors.forename: P
authors.initials: P
authors.lastname: Busson
authors.forename: G
authors.initials: G
authors.lastname: Rousselet
authors.forename: R
authors.initials: R
authors.lastname: Mahjoubi
authors.forename: P
authors.initials: P
authors.lastname: Flores
authors.forename: T
authors.initials: T
authors.lastname: Tursz
authors.forename: J P
authors.initials: JP
authors.lastname: Armand
authors.forename: N
authors.initials: N
authors.lastname: Azli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001853:Bone Marrow / Q000473:pathology; D002277:Carcinoma / Q000150:complications* / Q000382:microbiology / Q000473:pathology* / Q000556:secondary; D002648:Child; D005260:Female; D005335:Fever of Unknown Origin / Q000209:etiology*; D006566:Herpesviridae Infections / Q000150:complications / Q000473:pathology; D004854:Herpesvirus 4, Human; D006801:Humans; D007955:Leukemoid Reaction / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology*; D009361:Neoplasm Invasiveness; D010257:Paraneoplastic Syndromes / Q000209:etiology; D011859:Radiography; D014412:Tumor Virus Infections / Q000150:complications / Q000473:pathology