Occult nodal metastases in T1-T2cN0 oral squamous cell carcinoma: Correlation between sentinel node positivity and completion neck dissection analysis.

OBJECTIVES: Sentinel node procedure (SN) is a standard procedure that has shown its safety and effectiveness for T1/T2 cN0 oral squamous cell carcinoma (OSCC), with completion neck dissection (CND) for patients with positive SN. The aim of this study was to characterize the nodal involvement in a cohort of SN + OSCC. MATERIALS AND METHODS: Patients with T1/T2 cN0 OSCC with positive SN with CND were included in this single-center, prospective cohort study between 2000 and 2013. RESULTS: 54/301 patients had at least one positive SN. In 43/54 (80 %) cases, only the SN(s) were invaded; with only one SN involved (SN+=1) in 36/54 (67 %) cases. No predictive factors of nodal involvement in the CND were found considering the followings: SN micro/macrometastases, primary tumor's depth of invasion (DOI), perineural spread, lymphovascular involvement, primary tumor location, T stage and extranodal extension. The SN micrometastatic involvement (n = 22) was significantly associated with only one SN + CND- (p = 0.017). In the group of patients with unique micrometastatic involvement in the SN (n = 20/54), there was a higher isolated nodal recurrence free time (p = 0.017). CONCLUSION: 80% of T1/T2 cN0 OSCC with positive SN had no other lymph node metastases in the CND, questioning the potential benefits of this procedure. Predictive factors such as the size of the SN metastasis need to be tested to stratify the risk of positive non-SN lymph nodes leading to a personalized treatment, lowering the therapeutic morbidity while maintaining the oncologic safety.

Long-term outcomes and safety after reirradiation in locally recurrent nasopharyngeal carcinoma in a non-endemic area.

PURPOSE: To determine outcomes and toxicities after reirradiation for locally recurrent nasopharyngeal carcinoma (rNPC) and to apply a prognostic index in a non-endemic region. METHODS: We retrospectively reported progression-free survival (PFS), overall survival (OS), and treatment-related toxicities in patients treated with curative intent for locally rNPC. We applied the prognostic model for OS and grade 5 radiotherapy (RT)-related toxicities published by Li et al. and evaluated its prognostic accuracy by receiver operating characteristic (ROC) curve analysis. RESULTS: Between 2005 and 2018, 33 patients were treated for rNPC in our institution. Median follow-up was 60 months. The mean time to local recurrence was 75 months. Six (18%) patients had a persistent grade 3 toxicity from a previous RT course. The median re-RT dose was 66 Gy. After re-RT, 13 patients had local failure and 3 patients had metastatic recurrence. Median PFS was 18 months with a 5-year PFS rate of 29%. Median OS was 35 months with a 5-year OS rate of 37%. Grade 3 or higher toxicities rate was 74%. There were 21% grade 5 toxicities. The median time to a grade 5 toxicity was less than 6 months following re-RT. The prognostic nomogram was not predictive for OS or grade 5 toxicities. CONCLUSION: Reirradiation of rNPC is an effective treatment but is associated with a high rate of life-threatening toxicity. Stratification of patients based on their risk of developing severe toxicity is needed to select patients who will most likely benefit from re-RT.

Oncologic outcomes, prognostic factor analysis and therapeutic algorithm evaluation of head and neck mucosal melanomas in France.

BACKGROUND: Head and neck mucosal melanoma (HNMM) is aggressive and rare, with a poor prognosis because of its high metastatic potential. The two main subtypes are sinonasal (sinonasal mucosal melanoma [SNMM]) and oral cavity (oral cavity mucosal melanoma [OCMM]). Consensual therapeutic guidelines considering the primary tumour site and tumour-node-metastasis (TNM) stage are not well established. MATERIAL & METHODS: Patients with HNMM from the prospective national French Rare Head and Neck Cancer Expert Network database between 2000 and 2017 were included. Clinical characteristics, treatment modalities, outcomes and prognostic factors were analysed. RESULTS: In total, 314 patients were included. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 49.4% and 24.7%, respectively, in the surgery group; no long-term survivors were observed when surgery was not feasible. Moreover, even after surgery, a high recurrence rate was reported with a median PFS of 22 months. In multivariate analysis, Union for International Cancer Control (UICC) stage and tumour site correlated with PFS and OS. Postoperative radiotherapy (PORT) improved the PFS but not OS in patients with small (T3) SNMM and OCMM tumours. Nodal involvement was more frequent in patients with OCMM (p < 10-4), although, as in SNMM, it was not a significant prognostic predictor. CONCLUSION: Even early HNMM was associated with poor oncologic outcomes due to distant metastases despite surgical resection with clear margins. Lymph node metastases had no impact on the prognosis, suggesting treatment de-escalation in cervical node management. PORT might be useful for local control.

Ethmoid tumor and oncogenic osteomalacia: Case report and review of the literature.

INTRODUCTION: Oncogenic osteomalacia is a very rare disease usually caused by a phosphaturic mesenchymal tumor, particularly the "mixed connective tissue type", secreting FGF-23 hormone. OBJECTIVE: The authors report a case of ethmoid tumor associated with oncogenic osteomalacia and discuss management based on a review of the literature. CASE SUMMARY: A 41-year-old woman with multiple fractures causing major disability was diagnosed with early-onset osteoporosis. CT scan followed by MRI, performed due to the concomitant presence of nasal obstruction, showed a right ethmoid tumor in contact with the dura mater and periorbital tissues, but with no signs of invasion. Endoscopic resection was performed with reconstruction of the defect of the cribriform plate by a nasoseptal flap. Nasal and bone symptoms subsequently resolved. Histological examination revealed a phosphaturic mesenchymal tumor. DISCUSSION: Twelve cases of mesenchymal tumor of the ethmoid sinus associated with oncogenic osteomalacia have been reported to date. FGF-23 assay and whole-body MRI with STIR sequence are useful for the diagnosis. A very favorable outcome is observed after surgical treatment in the majority of cases.

Sentinel node biopsy in early oral squamous cell carcinomas: Long-term follow-up and nodal failure analysis.

OBJECTIVES: Evaluate the reliability of sentinel node biopsy (SNB) in T1/T2 cN0 oral squamous cell carcinoma (OSCC), and compare recurrence-free time (RFT) and overall survival (OS) between patients undergoing SNB and neck dissection (ND). PATIENTS AND METHODS: Patients with T1/T2 cN0 OSCC underwent SNB followed by systematic ND in the first cohort and SNB followed by selective ND in case of positive sentinel nodes (SN) in the second cohort. RESULTS: A total of 229 patients were followed (first cohort 50, second cohort 179). SNs were successfully detected in 93.9% (215/229) of cases. Median follow-up was 5.6 years. Recurrence occurred in 38/215 patients, with isolated nodal recurrence in 18/215 patients. At 5 years, the rate of recurrence-free patients was 80.0% and the rate of patients without isolated nodal recurrence was 90.4%. Negative predictive value of SNB was 92.7%. No statistically significant difference was observed between the two groups regarding RFT and OS. In 83% (10/12) of ipsilateral isolated nodal recurrences, primary tumor was located in anterior part of oral cavity. Only 43% (3/7) of SN+ patients with nodal recurrence were eligible for salvage surgery, compared to 91% (10/11) of SN- patients. SNB resulted in fewer complications than ND (8% vs 28%, p < 0.0001). CONCLUSION: SNB is a reliable staging tool for T1/T2 cN0 OSCC, without adverse effect on patient survival and fewer complications. No late recurrences occurred in long-term follow-up. Close follow-up is mandatory for SN+ patients, who are at higher risk of nodal recurrence and have worse prognosis.

[Oral cavity cancers among young people: Clinical results and prognostic analysis]. / Cancers de la cavité buccale chez les sujets jeunes: résultats thérapeutiques et analyse de facteurs pronostiques.

PURPOSE: Squamous cell carcinomas of the oral cavity occurring in young people represent a specific entity. Its management and prognosis are controversial. We performed a retrospective chart review of all patients aged less than 40 years old and treated at Gustave-Roussy Cancer Centre for a squamous cell carcinomas of the oral cavity between 1999 and 2011. METHODS: Patients and tumour characteristics, type of treatment and follow-up data were collected. Survival data were analysed according to the methods of Kaplan-Meier and both univariate and multivariate analyses were performed to look for prognostic factors regarding overall survival and progression-free survival. RESULTS: Sixty-three patients were identified. Median follow-up was 64 months. Most of the tumours were initially located in the mobile tongue (n=54, 85.7%). Overall 17 patients had died, including 15 from the treated cancer. Overall and progression-free survival rates at 5 years were respectively 79.6% and 68.6%. The corresponding 5 years local, regional and metastatic relapse free survival rates were 80%, 91% and 89% respectively. In the multivariate analysis only the absence of initial surgery (hazard ratio [HR]: 13.5 [2.0; 90.5]; P=0.007) was prognostic for overall survival, while alcohol abuse (HR: 0.37 [0.15; 0.9]; P=0.03) and the absence of surgery (HR: 13.6 [2.5; 74.2]; P=0.002) were associated with a decreased progression-free survival. A younger age (less than 30 year old) was not associated with the risk of recurrence or death. CONCLUSION: Survival rates and tumour control probabilities are relatively high among young patients suffering from squamous cell carcinomas of the oral cavity treated at a tertiary centre. The early identification of patients at risk of relapse is currently difficult. The balance between recurrence and treatment toxicity warrants further studies, both on the clinical level and for the development of prognostic biomarkers.

[Lacrimal duct tumors: diagnostic and therapeutic dilemmas]. / Tumeurs primitives des voies lacrymales: pièges diagnostiques et thérapeutiques.

INTRODUCTION: Fewer than 250 primary tumors of the lacrimal duct have been reported in the international literature. Because their signs and symptoms are nonspecific and usually subclinical, delayed diagnosis is common. Treatment for malignant epithelial tumors is surgical, with or without radiation. PATIENTS AND METHODS: The present study is a retrospective analysis of five patients with malignant lacrimal duct tumors. RESULTS: Three patients were diagnosed with carcinoma requiring wide en bloc surgical resection with surgical reconstruction. One underwent adjuvant radiation therapy. Another experienced simultaneous local and lymph node recurrence after 3 years and underwent curative surgery. Two additional patients were diagnosed with diffuse malignant large B-cell non-Hodgkins lymphoma. DISCUSSION: Early symptoms of lacrimal duct tumors are nonspecific and mimic acute dacryocystitis. Lacrimal system CT, MRI and rhinoscopy may allow for earlier diagnosis. Surgical treatment requires resection with wide margins and reconstruction of the medial canthal region. CONCLUSION: Only an early diagnosis can reduce the impairment related to surgery and the extent of the required reconstruction, as well as improve survival.

Quantitative methylation analyses of resection margins predict local recurrences and disease-specific deaths in patients with head and neck squamous cell carcinomas.

This study sought to determine whether the presence of hypermethylated genes in the surgical margins can predict local recurrences in head and neck squamous cell carcinomas (HNSCCs). We prospectively collected tumour and surgical margin specimens from patients with HNSCCs who had undergone surgical resections. Quantitative methylation-specific PCR (QMSP) of CDKN2A, CCNA1 and DCC were performed in these specimens and correlated with clinical data. Of the 42 patients eligible for the study, 27 were hypermethylation informative for the above three genes. This latter group was associated with longer disease-free survivals (P=0.007) and longer time to disease-specific deaths (P=0.004). Multivariate analyses confirmed hypermethylation non-informative tumours as an independent prognosticating factor for disease-specific deaths (risk ratio 3.8, P=0.026). Quantitative MSP of the margins of 24 hypermethylation informative tumours revealed that 11 patients had molecularly positive margins, of which, five developed disease-specific events (DSEs, three local recurrences and two metastases), compared to none in patients with molecularly negative margins, after a median follow-up of 48 months. Log-rank analyses showed that molecularly positive margins were associated with shorter time to local recurrences and disease-specific deaths (P=0.03 and 0.01, respectively). This study demonstrated that QMSP of hypermethylated promoters in surgical margins predicted all the local recurrences in our series of HNSCC patients. We have also identified hypermethylation non-informative tumours as an independent predictor for the development of DSEs.

[Verner-Morrison syndrome revealing a ganglioneuroblastoma in an adult]. / Syndrome de Verner-Morrison révélant un ganglioneuroblastome chez un adulte.

Most vasoactive intestinal peptide (VIP)-producing tumours are from epithelial origin. Tumours derived from the sympathetic nervous system can produce VIP as well. We report here the case of a Verner-Morrison syndrome in a 40-year-old woman revealing a metastatic ganglioneuroblastoma. The diarrhea resolved after the resection of primary tumour and liver metastases. Neuroblastic tumours occur extremely rarely in adults. Thus, the management of these tumours is poorly defined in adults.

Aggressive maxillary squamous odontogenic tumour in a child: histological dilemma and adaptative surgical behaviour.

A case of a maxillary osteolytic tumour is described in a 9-year-old boy. Histological analysis led to an initial diagnosis of benign squamous odontogenic tumour, although this was not straightforward due to swelling, and cellular pseudo-malignant and non-specific signs. Because of the young age of the patient, a local surgical tumourectomy was first chosen with respect to the mixed dentition. For 10 months, the evolution was satisfactory. Then, a very aggressive tumoural recurrence with lip and palate infiltration led to doubts as to the histologic nature of the tumour. Efficient collaboration between several specialized pathologist teams finally confirmed that this was a squamous odontogenic tumour but in a very aggressive form. Radical surgery was then carried out.

Hyperselective intra-arterial preoperative chemotherapy in patients with squamous cell carcinoma of the oral cavity: preliminary results.

OBJECTIVES: To investigate radiological response and findings after Intra Arterial Chemotherapy (IAC) for patients with Squamous Cell Carcinoma (SCC) of the oral cavity. MATERIALS AND METHODS: Patients received 1-2 cycles of IAC. Radiological assessment was performed on day 7 and day 21 after each cycle using CT scan and MRI. RESULTS: Six patients (median age: 52, ranging 46-60; male/female: 5/1) received 10 cycles (4 patients received 2 cycles). Primary tumors were floor of the mouth (4 patients) and oral tongue (2 patients). TNM classification was T2N0-2b in 3 patients and T4N0-1 in 3 patients. All patients had good locoregional/systemic tolerance and 3 showed clinical objective response (OR). Four patients were evaluable on both CT and MRI, 1 patient on MRI only and 1 patient did not tolerate imaging. Three patients showed OR both on CT and MRI, 1 patient showed stable disease (SD) on CT and OR on MRI and 1 patient showed SD on MRI. Contrast-enhancement of hemiperfused tongue was reported in all evaluable patients. Two patients presented intratumoral necrosis and 5 patients displayed local edema (MRI). One patient had modification of the sternocleidomastoid muscle after IAC. CONCLUSION: Radiological modifications were observed in the infused area and correlated well with clinical response. This study is ongoing.

[Role and perspectives of sentinel node biopsy in head and neck tumors]. / Place et perspectives du ganglion sentinelle dans les tumeurs des voies aérodigestives supérieures.

PURPOSE: To evaluate the accuracy of sentinel node biopsy for assessing the neck status for those patients with squamous cell carcinoma T1T2N0 of oral cavity. PATIENTS AND METHODS: 55 patients were included in a prospective study between 2000 and 2003. 53 underwent a sentinel node biopsy (SNB) followed by an elective neck dissection (END). Pathological examination with stepped serial sectioning and immunohistochemistry of sentinel node (SN) has been compared with routine pathology examination of remaining END nodes. RESULTS: 12 patients had a positive SN. No false negative was found. Patient follow up on, at less of 3 years, did not show any node recurrence for those patients with negative SN. After that study, 44 patients had a SNB without END. 7 patients had a positive SN. Follow up showed a node recurrence for 3 patients. In two of these, pathological reexamination showed a micrometastase in SN. SN failure rate is less than 3% for those 99 patients. CONCLUSION: SNB is a liable procedure. Failure rate is the same as in END. We plan to use this procedure in orophyngeal tumors where it could be possible to reduce irradiation fields and treatment sequels for those patients with negative SN.

[Usefulness of panfungal PCR for the diagnosis of fungal infection in immunocompromised patients]. / Intérêt de l'amplification génique à l'aide d'amorces universelles dans le diagnostic des infections fongiques chez le patient immunodéprimé.

The diagnostic of invasive fungal infection is often difficult because of the low sensitivity of fungal culture from infected tissues. Here we have assessed the ability of a panfungal PCR targeted on the DNA region encoding the RNA genes followed by sequencing of the amplification products to detect and identify fungi from tissue biopsies. This assay allowed us to identify the microorganism responsible for an invasive fungal infection in three of our patients. In two cases, hepatosplenic candidiasis was suspected and Candida albicans DNA was detected from liver biopsies. The third patient was cared for a thymome and developed a manubrium osteitis caused by Scedosporium apiospermum.

Synovial sarcomas of the head and neck: CT and MR imaging findings of eight patients.

BACKGROUND AND PURPOSE: Synovial sarcomas are soft-tissue tumors that rarely occur in the head and neck. The purpose of this study was to evaluate their CT and MR imaging appearance and to show that they may have a surprisingly benign imaging appearance. METHODS: Eight patients with histologically proved synovial sarcoma underwent CT; additionally, MR imaging examinations were performed in five of the eight cases. Attenuation and signal intensity on CT scans and MR images, respectively, were studied by two radiologists. They analyzed the location, size, margins, homogeneity, presence of adenopathies and infiltrative signs, and enhancement after injection of contrast medium. RESULTS: Four tumors were located in the hypopharynx, two arose from the infratemporal fossa, one arose from the maxillary sinus, and one arose from the faucial tonsil. Tumor sizes ranged from 27 to 70 mm. On CT scans and MR images, six lesions were homogeneous and well defined, with smooth margins. The remaining tumors were heterogeneous. In two cases, adjacent tissues were invaded. Calcifications were observed in one case and adenopathy in two cases. In three cases, the lesions were isointense on T1-weighted MR images and hypointense on T2-weighted MR images, and in the other two cases in which MR imaging was performed, the lesions were both isointense and hypointense on both T1- and T2-weighted images. Only the two local recurrent lesions were multilocular. CONCLUSION: Synovial sarcomas are aggressive sarcomas that may appear "benign" in some cases. In a young man, a synovial sarcoma may be suspected when a well-demarcated, homogeneous lesion is found in the head and neck.

Salivary gland tumors of the mandible.

Primary central salivary gland carcinomas of the mandible are uncommon neoplasms. Consequently, their proper diagnosis is often in doubt. We retrospectively studied the cases of 16 patients treated at The University of Texas M. D. Anderson Cancer Center and the Institut Gustave Roussy from 1950 to 1990. Patients ranged in age from 24 to 76 years (mean, 51 years). Nine patients were women and seven were men. Each case involved either the angle or the posterior body of the mandible. Swelling, pain, and trismus were the most frequent complaints. For all patients, radiography revealed a cystic defect resembling an osteolytic odontogenic lesion or metastasis. Five histologic types of carcinoma were diagnosed: seven cases of mucoepidermoid carcinoma (five low-grade and two high-grade), four cases of adenoid cystic carcinoma, two cases of adenocarcinoma, two cases of acinic-cell carcinoma, and one case of epithelial-myoepithelial carcinoma. All patients were treated with wide surgical excision. Eight patients received postoperative irradiation. Five patients with low-grade mucoepidermoid carcinoma, two with acinic-cell carcinoma, and one with epithelial-myoepithelial carcinoma were free of disease 2 to 15 years after initial treatment (mean, 6.2 years). Two patients with adenoid cystic carcinoma are living with lung metastasis. The remaining six patients died of their carcinomas within 4 years after initial treatment. Because of their unique morphology and clinical behavior, these tumors should be distinguished from other intraosseous neoplasms of the mandible, including those with clear-cell patterns.

Gallium scan in the evaluation of post chemotherapy mediastinal residual masses of aggressive non-Hodgkin's lymphoma.

Optimal evaluation of residual masses of non Hodgkin's lymphomas (NHL) after chemotherapy is of major importance, and gallium scan (GS) is routinely used for this purpose, particularly for mediastinal sites. However, sensitivity and specificity of GS in this setting has been diversely appreciated and needs to be more accurately defined especially if radiotherapy is not planned. A retrospective analysis selected all the patients treated in a single institution for aggressive NHL who presented a residual mass in the mediastinum after chemotherapy and who were evaluated by GS. The value of GS for distinguishing true complete responses (CR) from partial responses (PR) was analyzed in patients who were either submitted to resection of their residual mass or followed up without further treatment after GS. A residual mass with mean perpendicular diameters measuring 4.1 cm x 2.8 cm was found in 42 patients and was GS positive in 8 cases and negative in 34 cases. After GS, radiotherapy was delivered to 10 patients, but 12 patients underwent resection of their residual mass and 20 were followed up without further treatment. In the patients who did not receive radiotherapy, 3 false positive and 6 false negative GS results were disclosed. The specificity and the sensitivity of GS were 88% and 25%, and its positive predictive value and negative predictive value 40% and 78%, respectively. GS was not sufficiently reliable to evaluate post chemotherapy residual masses. Surgical resection of residual masses should be considered particularly in young patients. Patients in true CR should be spared pointless radiotherapy and its late side effects, while patients in PR may benefit from further intensified chemotherapy followed by radiotherapy.

[Primary synovial sarcoma of head and neck. Materials of The Gustave Roussy Institute. Report of 13 cases]. / Synovialosarcomes cervico-faciaux. Expérience de 1'Institut Gustave Roussy. A propos de 13 cas.

This report presents the result of our experience with 13 primary synovial sarcoma of the head and neck. The 9 males and 4 females had a median age of 32 years. The predominant location of the tumor was the pharynx, treatment consist of surgical excision alone or associated with post-operative radiotherapy or chemotherapy. Mean follow-up was 48 month. Local recurrence occurred in 2 patient, 4 patient died of pulmonary metastasis. The five year survival rate was 55%. Favorable prognostic findings included age < 20 years and complete initial resection.

Cytotoxic protein expression in natural killer cell lymphomas and in alpha beta and gamma delta peripheral T-cell lymphomas.

Lymphomas with T-cell phenotype represent a heterogeneous group of diseases differing in histopathology, tumour site, and cell origin. They include peripheral T-cell lymphomas (PTCLs) derived from alpha beta cells, but also some recently recognized entities such as gamma delta, hepatosplenic lymphomas and natural killer (NK) cell lymphomas. Only a few studies have investigated the possibility that at least some PTCLs could be derived from lymphocytes with cytotoxic potential. In order to investigate this possibility, 60 cases of PTCL, including 27 cases expressing the alpha beta T-cell receptor (TCR alpha beta), 15 TCR gamma delta cases and 18 cases expressing neither TCR (TCR silent), as well as 14 cases of NK-cell lymphomas, were studied by immunohistochemistry for the expression of TIA-1, perforin, and granzyme B proteins. Expression of TIA-1 is characteristic of cytotoxic cells regardless of their activation status, whereas expression of perforin and granzymes is highly increased in activated cytotoxic cells and correlates with the induction of cytolytic activity. All NK-cell lymphomas (11 sinonasal, three systemic cases) expressed TIA-1, perforin, and granzyme B in most tumour cells. All gamma delta PTCLs (15 cases) expressed TIA-1 protein in most tumour cells, with a different cytotoxic antigen profile in hepatosplenic gamma delta PTCL (TIA-1+, perforin-, granzyme B-) and in non-hepatosplenic gamma delta PTCLs (three nasal, one skin, one lung), the latter expressing the three cytotoxic proteins. Of the 45 cases of alpha beta and TCR silent PTCL, 15 (33 per cent) were considered to be derived from cytotoxic lymphocytes with expression of at least one cytotoxic protein (TIA-1, 15/45; perforin, 10/41; granzyme B, 14/38) in tumour cells. This cytotoxic protein expression appeared to be related to the site of localization, since 7/13 (54 per cent) extranodal and only 8/32 (25 per cent) nodal alpha beta and TCR silent PTCLs expressed TIA-1, and to histology, since this pattern was observed in a proportion of anaplastic (6/8, 75 per cent) and pleomorphic (8/17, 47 per cent) lymphomas, but not in AILD-type NHL (0/16). Taken together, our data suggest that NK-cell lymphomas and non-hepatosplenic gamma delta PTCLs represent tumours of activated cytotoxic NK cells and gamma delta T cells, respectively; that hepatosplenic gamma delta PTCLs represent tumours of non-activated cytotoxic gamma delta T cells; and that a small proportion of alpha beta and TCR silent PTCLs, mostly extranodal cases, or nodal anaplastic lymphomas, represent tumours of cytotoxic T cells.

Detection on liver tissue sections of S-phase markers in synchronized cycling rat hepatocytes by SIMS microscopy.

The aim of this study was to localise two ionic S-phase markers in tissue sections using SIMS microscopy: aluminium as a potential endogenous marker and bromine as an exogenous marker after in vivo injection of bromodeoxyuridine (BrdU). This study was performed in an experimental model of hyperplastic proliferation after partial hepatectomy in rat. Aluminium was never detected in nuclei which were positive or negative for tritiated thymidine uptake, as determined by autoradiography in tissue prepared by cryotechniques. In contrast, bromine of BrdU was found in hepatocyte nuclei. However, there was a discrepancy between SIMS bromine images and BrdU immunohistochemistry detection which appears more sensitive. This is probably due to problems of stereology intrinsic to the correlation method which requires serial sections for this multi-instrumental approach.