The spectrum of micronodular thymic epithelial tumours with lymphoid B-cell hyperplasia

AIMS: A rare type of thymoma, micronodular thymoma with lymphoid B-cell hyperplasia, was recently reported by Suster and Moran. Thymic epithelial tumours with a similar pattern but with varied cytological features of the tumour cells are analysed. METHODS AND RESULTS: A total of 11 cases of thymic epithelial tumours characterized by micronodular proliferation of tumour cells separated by abundant lymphoid stroma with prominent germinal centres were reviewed clinicopathologically and examined immunohistochemically. The presence of Epstein-Barr virus (EBV) genome was also examined by in-situ hybridization. Based on the morphology of tumour epithelial cells, cases were subdivided into four groups: group 1 (two cases) having spindle epithelial cells; group 2 (two cases) showing an admixture of spindle and polygonal epithelial cells; group 3 (five cases) having polygonal epithelial cells, with mild to moderate cytological atypia in four cases, and group 4 (two cases) representing lymphoepithelioma-like carcinoma. The degree of cytological atypia and the number of tumour cells positive for MIB-1 and p53 gradually increased towards group 4. The abundant lymphoid stroma in all cases contained many CD20-positive B-cells and CD3 and CD45RO-positive T-cells. CD99-positive immature T-cells were present in all cases of groups 1 and 2 and in most cases of group 3, but not in both cases of group 4 tumours. IgG, IgM and IgD-positive plasma cells and lymphocytes were also present in all cases, more prominent in those of groups 3 and 4. The EBV genome was detected in only a few lymphocytes in five cases. CONCLUSIONS: The tumours in this series belong to a distinct category of thymic epithelial tumours and each of the above groups may constitute a spectrum in the continuum of cytological atypia. The aetiological relationship of EBV with these tumours could not be proved. The lymphoid B-cell hyperplasia may result from a host immune response and may suggest a favourable clinical course of this type of tumour.     

Thymic epithelial tumour progression in an SV40T transgenic mouse model

 There have been several reports that thymoma in human is a progressive disease, and that thymoma and thymic carcinoma form a continuum. We established a stable line of SV40T transgenic mice, which consistently produced thymic epithelial tumours progressing to thymic carcinoma within a predictable time span. Using this animal model and a morphological approach, thymic epithelial tumour progression was studied with reference to sequential changes at different time points in animals aged from 3 to 32 weeks. At all ages, SV40T was expressed in the nuclei of thymic epithelial cells; in these transgenic mice we observed the entire spectrum from cortical type thymoma to thymic carcinoma. Thymic size tended to increase with ageing in SV40T TG mice. While younger mice had predominantly cortical (organoid) or cortical thymoma, older mice had well-differentiated thymic carcinoma (WDTC) or poorly differentiated thymic carcinoma. When SV40T TG mice (248 line) reached a certain age, carcinoma of the thymus was present in all of them. Cortical-type thymoma became malignant within a predictable time span, suggesting a cortical thymoma–carcinoma sequence. When the mice were 9 weeks of age, the thymuses formed gross masses compatible with cortical thymoma. At 14 weeks of age, WDTC appeared against the background of cortical thymoma. Poorly differentiated thymic carcinoma was found after 15 weeks and affected all animals over 23 weeks of age. Most thymic carcinomas coexisted in varying proportions with cortical-type thymoma. Medullary thymomas did not develop in the mice, and no transition from medullary-type thymomas to thymic carcinomas was observed. In this SV40T transgenic mouse model, thymic carcinoma is clearly preceded by cortical-type thymoma. These transgenic mice may provide an interesting model for the progression from cortical thymoma to WDTC and/or high-grade carcinoma. Received: 6 August 1996 / Accepted: 23 June 1997     

Recurrent thymoma: evidence for histological progression

The clinicopathological features of nine cases of recurrent thymomas have been studied. At presentation, all cases were histologically classified as thymomas with cortical differentiation, including predominantly cortical thymoma, cortical thymoma and well-differentiated thymic carcinoma. In five cases the morphological features of the recurrence(s) were suggestive of a histological progression of the tumour from predominantly cortical thymoma to cortical thymoma and/or well-differentiated thymic carcinoma, usually associated with a more advanced clinical stage, the latter indicating a clinical progression. These findings suggest that all types of thymoma with cortical differentiation are histologically and histogenetically related neoplasms, associated with a more aggressive clinical behaviour and a significant risk of recurrence. The overall outcome of patients with recurrent thymoma in this series was poor, since six patients (66.6%) died due to the disease, 2–14 years after the first diagnosis. The clinical implication of our findings is that thymomas with cortical differentiation always need careful follow-up, even in those cases which are not obviously invasive at onset.     

Thymic tumours in Denmark. A retrospective study of 213 cases from 1970-1993.

Histological slides of 213 thymic tumours were reviewed twice and classified according to Kirchner and Müller-Hermelink into 122 thymomas (syn. organotypic thymic epithelial tumours (TET)), 58 thymic carcinomas (syn. non-organotypic TET) and 16 lymphomas. Tumour heterogeneity (i.e. features of two subtypes in one tumour) appeared in 38% of the organotypic TET. The overall diagnostic correspondence between the reviews of the 122 organotypic TET was 48%. By reducing the five diagnostic groups to three: organotypic TET benign (medullary and mixed thymomas), organotypic TET low-grade (organoid and cortical thymomas and well-differentiated thymic carcinoma (WDTC)) and non-organotypic TET (usually high-grade thymic carcinomas), and minimising the effect of tumour heterogeneity in this way, the diagnostic correspondence increased to 82%. Correlating histological type with stage, we found that 80% of medullary and 87% of mixed thymomas were stage I, that 85% of cortical and 81% of WDTC were stage II or III, and that non-organotypic TET were stage II or III (86%) or stage IV (14%), respectively. It is suggested to report on the heterogeneity of a given case of thymic epithelial tumour in the pathology reports and give the approximate percentage of each component, telling the clinician which component may determine the prognosis.     

Histopatholgical spectrum of thymic neoplasms: twelve-year experience at a referral hospital in north India

This study was undertaken to determine the histopathological spectrum and clinical profile of thymic neoplasms at a tertiary referral care centre. A total of 96 thymectomy specimens were received during the study period (1992-2004), which consisted of 54 neoplasms and 42 benign lesions. Among the neoplasms there were 48 thymic epithelial tumors, 3 thymolipomas and 3 thymic carcinoids. The former comprised of 36 male (75%) and 12 female patients (25%) ranging in age from 2-70 years (mean 37 years). Among paraneoplastic syndromes in thymic epithelial tumours, 27 out of 48 (56.25%) cases were associated with myasthenia gravis and one case was associated with pure red cell aplasia. The most frequent histological subtype was cortical thymoma (43.24%) followed by predominantly cortical (24.32%) and well-differentiated thymic carcinoma (18.92%). On staging, all cases of mixed and predominantly cortical subtype were stage 1 whereas one medullary and 2 cortical thymomas and 4 well differentiated thymic carcinoma (WDTC) showed pleural and pericardial invasion (stage III). This study has revealed that half of thymic epithelial tumours presented as myasthenia gravis. The cortical thymoma was the most frequently encountered histologic subtype and most commonly associated with myasthenia gravis.     

Thymoma in childhood: a clinicopathological study of five cases

The histological and clinical findings in five cases of thymoma arising in paediatric patients have been studied. The age range was 11-15 years and no patient was affected by myasthenia gravis. All tumours were macroscopically encapsulated, but two of them displayed evidence of microscopic capsular invasion. Histologically, four cases were of the predominantly cortical type (organoid thymoma) with prominent areas of medullary differentiation and Hassall's bodies; one case was of the cortical type. All patients are alive and disease-free 3 months to 9 years after surgery. These findings suggest that thymoma in the paediatric age group may be characterized by fairly uniform clinicopathological features, with a low rate of association with myasthenia gravis and a favourable prognosis.     

Fine needle aspiration cytology of invasive micropapillary carcinoma of the breast

AIM: To determine the pathognomonic diagnostic cytological features of invasive micropapillary carcinoma of the breast which is a poor prognostic subtype of infiltrating ductal carcinoma. METHODS: A series of 20 histologically proven tumours were reviewed retrospectively to evaluate the various cytological features, including tumour morules, isolated malignant cells, staghorn epithelial structures, mucinous background and apocrine metaplasia. RESULTS: Tumour morules formation and isolated malignant cells were the two most reliable and constant cytological features, being present in 75% (15/20 cases) of cases. Staghorn epithelial structures were present in 35% (7 cases). Mucinous background (2 cases, 10%) and apocrine metaplasia (4 cases, 20%) of the tumour cells were seen in a few cases only and did not appear very helpful. CONCLUSION: Tumour morules formation, isolated malignant cells and staghorn epithelial structures are the most reliable cytological features, and the presence of these should raise suspicion of invasive micropapillary carcinoma.     

Evaluation of a histogenetic classification for thymic epithelial tumours

We reviewed 87 thymic epithelial tumours from Chinese patients and typed them according to the Marino and Müller-Hermelink classification as updated by Kirschner and Müller-Hermelink in 1989. Related categories were grouped for statistical analyses; group 1, medullary thymoma and mixed thymoma; group 2, cortical predominant thymoma; group 3, cortical thymoma and well-differentiated thymic carcinoma; group 4, other thymic carcinomas; and group 5, unclassified. Group 3 tumours were more frequently associated with the myasthenia gravis syndrome compared with group 1 tumours ( P =0.001). They also presented at a more advanced stage. Groups 1 and 2 showed an excellent prognosis (100% survival at 10 years). The 10-year survival for groups 3 and 4 patients was 40% and 30% respectively. Pure medullary thymoma made up a higher proportion of our cases (10.3%) than those of a similar Caucasian study (5.3%). The eight thymic carcinomas (group 4) included two thymic lymphoepitheliomas. We conclude that the histogenetic classification evaluated shows a clear correlation with prognosis and clinical features, even when tested on separate geographic groups, where pathogenetic factors may be different. A common approach to classification of thymic epithelial tumours would greatly facilitate future studies on these possible differences.     

Renal epithelioid angiomyolipoma: a study of six cases and a meta-analytic study. Development of criteria for screening the entity with prognostic significance

Aims:  Renal epithelioid angiomyolipoma (EAML) is only described in case reports or in multi-institutional small series. The aim was to report cases seen at our institution and to perform a meta-analysis based on a literature review.
Methods and results:  Six EAML cases seen at our institution were reviewed and a meta-analysis performed using cases retrieved from a literature review. There were a total of 69 cases for review. The male:female ratio was 1:3. In the absence of areas of typical AML, useful features in distinguishing EAML from epithelial renal neoplasms include: extreme degree of cytological atypia, histiocytoid appearance, presence of melanocytic pigments, solid architecture with the absence of frequent areas of alveolar pattern, tubulo-papillary formation and scarring. A fatal outcome, distant or lymph node metastasis, venous invasion and local recurrence were considered as adverse events and occurred in 40% of cases over a period of follow-up of 3–60 months (mean 22.5 ± 18 months). Tumours with an unfavourable outcome showing marked cytological atypia and extensive tumour necrosis were larger (135 ± 43 mm) than those with a favourable outcome (79 ± 50 mm) ( P  < 0.002), and predominantly occurred in men.
Conclusions:  Renal neoplasms with certain unusual features should be investigated immunohistochemically to rule out the possibility of EAML. The frequency of adverse outcome is lower in EAML than in renal cell carcinoma.     

DNA content in gallbladder carcinoma: a flow cytometric study of 96 cases

The DNA content in gallbladder carcinoma and its relation to histological and cytological features was studied in 79 primary gallbladder carcinomas and 16 metastases. Abnormal DNA content was observed in 48 (51%) of 95 cases. In primary carcinomas, 44 (55.6%)showed a diploid DNA content, and 35 (44.4%) were aneuploid. The majority of the metastatic lesions were aneuploid DNA (81.3%; P =0.006). Marked differences in the coefficient of variation estimated by manual, Kosugi and Dean methods were detected ( P =0.005). Seventy-one per cent of early gallbladder carcinomas had a normal DNA content. In contrast 54% of the cases with subserosal or serosal infiltration had normal DNA content. In primary tumours the degree of architectural atypia had a close relationship with the degree of cellular atypia ( P =0.00001). Only two (15%) of 13 cases with mild architectural atypia, and 34 (51.5%) of 66 cases with marked architectural atypia were aneuploid. Only one (10%) of 10 cases with mild cellular atypia and 35 (51%) of 69 with high cellular atypia had abnormal DNA content ( P =0.01) The importance of DNA content as a marker in gallbladder carcinoma remains uncertain and its clinical importance requires further clinicopathological studies.     

Polymorphous sweat gland carcinoma

We describe nine cases of a distinctive cutaneous neoplasm showing features of eccrine adnexal differentiation that were characterized by their variegated histological appearance and low-grade malignant behaviour. The term polymorphous sweat gland carcinoma is proposed to designate these lesions. The tumours presented as large, longstanding, slow growing, dermal nodules showing a marked predilection for the extremities. Six patients were women. The patients were aged 42–70 years (mean, 59.8 years). Histologically, the lesions were characterized by a highly cellular proliferation displaying a variety of growth patterns, including solid, trabecular, tubular, pseudopapillary and cylindromatous, with prominent stromal changes including haemorrhage, hyalinization and cystic change, and displaying moderate cytological atypia and mitoses. Focal areas showing features associated with eccrine differentiation (i.e. tubular structures, small glandular lumina) could be identified in all cases. Clinical follow-up in six cases showed that two of the lesions recurred locally over a period of 3–6 years, and one tumour metastasized to regional lymph nodes 3 years after excision. Polymorphous sweat gland carcinoma should be considered in the differential diagnosis of neoplastic epithelial dermal proliferations; complete but conservative surgical excision appears to be the treatment of choice for these lesions.     

Polymorphous low-grade adenocarcinoma of the major salivary glands: report of three cases in an unusual location

AIMS: Polymorphous low-grade adenocarcinoma (PLGA) is the second most common type of malignant neoplasm in minor salivary glands. Its origin in major salivary glands is considered exceedingly rare. Herein, we present three cases of de novo PLGA arising in major salivary glands. METHODS AND RESULTS: Three cases of PLGA were identified in a large series of primary tumours of major salivary glands. We investigated their clinicopathological profiles, including immunohistochemical features. The three patients (two men and one woman) were 51, 65, and 79 years old. The tumours were 20-30 mm large; two were in the parotid gland and one in the submandibular gland. Histologically, all the tumours had a polymorphous architectural pattern showing predominantly solid, tubular, and cribriform features and invasive growth. Papillary areas were observed focally in two tumours and an 'Indian-file' array in one. The tumour cells had a bland cytological appearance and low mitotic count. Two tumours showed perineural invasion. No preexisting pleomorphic adenoma component was identified. In all cases, tumour cells were positive for epithelial markers, S100 protein, and vimentin but negative for alpha-smooth muscle actin, muscle-specific actin, and glial fibrillary acidic protein. Proliferative activities assessed with the Ki67 labelling index were 4.3%, 7.1%, and 7.6%; no p53 overexpression was observed. Two patients had local recurrence, but none had metastasis or died of tumour. CONCLUSIONS: PLGAs arising in major salivary glands and those in minor salivary glands have similar clinicopathological and immunohistochemical characteristics. It is important to recognize that PLGA can occur ab initio in the major salivary glands, although it is extremely rare.     

Central atypical papillomas of the breast: a clinicopathological study of 119 cases

The clinicopathological features of central intraductal papillomas of the breast presenting with florid usual ductal hyperplasia or atypical ductal hyperplasia (ADH) were analyzed in a retrospective series of 119 patients, whose lesions were sent to the Armed Forces Institute of Pathology from 1976 to 1990. After histological review considering predefined morphological and quantitative criteria, the 119 central papillomas were classified into 22 papillomas with florid usual ductal hyperplasia (18%), 40 papillomas with focal atypia (34%), 24 atypical papillomas (20%) and 33 carcinomas arising in a papilloma (28%). After a median period of follow-up of 110 months, 16 recurrences (5 papillomas, 2 carcinomas arising in a papilloma, 4 ductal carcinomas in situ, 5 invasive carcinomas) occurred. No statistically significant difference was observed in relation to recurrence for the various categories of papillomas. The presence of epithelial hyperplasia, ADH or lobular neoplasia in the surrounding breast as well as infarction of the papilloma were significant predictive factors of recurrence (P=0.02 and P=0.005, respectively, log-rank test). The main reason for the observed low rate of significant recurrences in this series was that epithelial atypia (whether comprising 20% or 60% of the papillary lesion) was, in most of the cases, localized in a confined lesion that was completely excised.     

''Organoid'' thymoma: a well-differentiated variant with distinctive clinicopathological features

The present paper describes the clinical, histological and immunohistochemical features of five cases of 'organoid' thymoma. The histological hallmark of this lesion is the prominent and diffuse 'organoid' pattern, defined by the presence of several areas of medullary differentiation. These areas, which are strictly reminiscent of the medullary area of the normal thymus, are scattered within a neoplastic tissue resembling the thymus cortex, the overall appearance mimicking that of normal thymus. All cases shared common clinical features; they were non-invasive or minimally invasive tumours arising in young or middle-aged female patients. Although the incidence of 'organoid' thymoma is low (5.2% in our series), our morphological, immunohistochemical and clinical data suggest that this peculiar tumour may represent a well-differentiated variant of thymoma, with low-grade aggressiveness and a distinct clinicopathological profile.     

Cytological features of dedifferentiated adenoid cystic carcinoma of the trachea

Adenoid cystic carcinoma (AdCC) is a distinct type of carcinoma, and cytological examination has been recognized as a useful tool in its diagnosis. Dedifferentiation is defined as the abrupt transformation of a low‐grade tumor into a tumor with high‐grade components. Albeit extremely rare, dedifferentiated AdCC has been reported: however, the cytological features of this tumor have not been documented. We observed a case in which a 66‐year‐old Japanese male had stenosis and thickness of the lower tracheal and bronchial walls. Cytological smears of a bronchial brush specimen revealed features typical for low‐grade AdCC. However, a few cohesive epithelial cell clusters composed of large, atypical polygonal cells with large nuclei and conspicuous nucleoli also were present. This component was considered to represent dedifferentiated carcinoma. Histopathological study of the resected bronchial tumor revealed dedifferentiated AdCC. The cytological diagnosis of conventional low‐grade AdCC is straightforward in most cases, although extremely rare, dedifferentiated carcinoma can occur within the conventional AdCC, and detection of a dedifferentiated component is possible in a cytological specimen because of obvious nuclear atypia. Therefore, careful observation is needed because cytologic diagnosis of dedifferentiated AdCC can help expedite treatment of this highly aggressive tumor. Diagn. Cytopathol. 2014;42:880–883. © 2013 Wiley Periodicals, Inc.     

Immunohistochemical assessment of proliferative activity in mammary adenomyoepithelioma

Aims : Two cases of adenomyoepithelioma of the breast were examined by immunohistochemistry to evaluate proliferative activity of epithelial and myoepithelial components. Methods and results : The tumours showed a bicellular pattern of gland-forming epithelial cells and proliferative myoepithelial cells with clear cytoplasm. They showed foci of monotonous growth of myoepithelial cells devoid of glands with low mitotic rate (1 ∼ 2/10 high-power fields) and mild cytological atypia. Immunohistochemically, the glandular cells were positive for epithelial membrane antigen, cytokeratin (KL-1 and CAM5.2) and carcinoembryonic antigen, whereas tumour cells with clear cytoplasm were reactive with muscle-specific actin (MSA), alpha smooth muscle actin, vimentin, and S100 protein but negative for desmin. Proliferative activities assessed by MIB-1(Ki-67)/MSA positive cell index were greater in myoepithelial cells in both cases (19.2% and 17.7%) as compared to those in epithelial cells (MIB-1/CAM5.2 index: 10.2% and 9.5%). Conclusions : These results might account for the previous findings that myoepithelial components predominate over the epithelial ones in an advanced stage of this tumour as well as in recurrent or metastatic lesions.     

Immunohistochemical assessment of proliferative activity in mammary adenomyoepithelioma

Aims: Two cases of adenomyoepithelioma of the breast were examined by immunohistochemistry to evaluate proliferative activity of epithelial and myoepithelial components. Methods and results: The tumours showed a bicellular pattern of gland-forming epithelial cells and proliferative myoepithelial cells with clear cytoplasm. They showed foci of monotonous growth of myoepithelial cells devoid of glands with low mitotic rate (1 ～ 2/10 high-power fields) and mild cytological atypia. Immunohistochemically, the glandular cells were positive for epithelial membrane antigen, cytokeratin (KL-1 and CAM5.2) and carcinoembryonic antigen, whereas tumour cells with clear cytoplasm were reactive with muscle-specific actin (MSA), alpha smooth muscle actin, vimentin, and S100 protein but negative for desmin. Proliferative activities assessed by MIB-1(Ki-67)/MSA positive cell index were greater in myoepithelial cells in both cases (19.2% and 17.7%) as compared to those in epithelial cells (MIB-1/CAM5.2 index: 10.2% and 9.5%). Conclusions: These results might account for the previous findings that myoepithelial components predominate over the epithelial ones in an advanced stage of this tumour as well as in recurrent or metastatic lesions.     

Deep penetrating naevus: clinicopathological study of 31 cases with further delineation of histological features allowing distinction from other pigmented benign melanocytic lesions and melanoma

AIMS: To examine a series of deep penetrating naevus (DPN) and discuss the differential diagnosis of pigmented, deep penetrating melanocytic lesions and their biological potential. DPN has been described as a variant of common acquired intradermal melanocytic naevus. DPN remains poorly recognized by pathologists, partly attributable to its relatively rare occurrence. METHODS AND RESULTS: Thirty-one cases of deeply pigmented lesions were studied. The patients included 17 females and 14 males with an age range between 3 and 56 years (mean 25.8, median 23). The common clinical sites were face (n = 10) back (n = 6) and lower extremity (n = 7). The clinical diagnoses included various benign melanocytic naevi, and malignant melanoma, as well as non-melanocytic lesions. Histologically, all cases presented as wedge-shaped lesions composed of fusiform cells but also epithelioid melanocytes, with pale cytoplasm and oval nuclei. Pigment was identified in melanophages but also within lesional melanocytic cells. Nine cases contained mitotic figures. Nine cases showed the coexistence of 'ordinary' common acquired naevocytes, and seven lesions showed overlapping features with either ordinary blue naevus or Spitz naevus. In 13 lesions there was at least one feature that may cause concern as to the biological nature of the tumour. These include asymmetry, cytological atypia, inflammation, or an 'expansile' advancing margin. Each tumour was treated by simple excision; one lesion recurred after 1 year. No tumour metastasized. CONCLUSIONS: DPN is a distinct variant of melanocytic naevus. In some cases the histological features overlap with other benign melanocytic lesions. Criteria for recognizing malignant examples remain unclear, but cytological atypia and low mitotic activity do not necessarily portend a sinister outcome.     

Thymoma: an integrated clinicopathological and immunohistochemical study

The clinicopathological features of 32 thymomas were reviewed and tumours were staged according to their degree of invasion. Their antigenic profiles were studied using monoclonal antibodies to cytokeratins (CAM 5.2 and DAKO-CK1), HNK-1 (Leu 7), and HLA-DR (TAL-IB5). Stage I (non-invasive) tumours were mainly of the spindle cell (SC) or predominantly lymphocytic (PL) types, whilst all the predominantly epithelial (PE) tumours were either locally invasive (stage II) or showed more extensive spread (stage III). Neoplastic epithelial cells all expressed cytokeratin, but varied in their degree of positivity. CAM 5.2 was more uniformly positive with cells at the periphery of tumour nodules and lining tubulo-cystic areas staining most strongly. DAKO-CK1 gave less uniform positivity but highlighted areas of medullary differentiation. HNK-1 was variably expressed in all tumour groups but was found more often in the invasive tumours (73 per cent stage III, 62 per cent stage II, 50 per cent stage I), particularly those of PE or mixed (M) type. In general, TAL-IB5 expression was lost in the more invasive thymomas. Focal medullary differentiation in tumours suggests a common origin for cortical and medullary epithelium, indicating that sub-division of tumours into cortical or medullary types is not valid. Immunohistochemistry may usefully complement clinical and macroscopic findings in the assessment of malignancy in thymoma.     

Thymic epithelial tumours: Evaluation of malignant grade by quantification of proliferating cell nuclear antigen and nucleolar organizer regions

Cellular proliferation was studied by quantification of proliferating cell nuclear antigen (PCNA) and argyrophilic nucleolar organizer regions (AgNORs) of cells in 29 thymic epithelial tumours: 8 noninvasive (7 cortical and 1 mixed) thymomas, 11 invasive/metastatic (all cortical) thymomas, and 10 thymic carcinomas. Thymic carcinoma showed the highest percentage of cells positive for PCNA (14.73±5.419%) and the largest mean number of AgNORs per nucleus (4.89±0.756). The mean percentage of PCNA-positive cells and number of AgNORs in thymoma groups were as follows: in noninvasive thymoma 2.96±1.256% and 2.73±0.647, respectively, and in invasive/metastatic thymoma 4.41±1.823% and 3.68±1.148, respectively. The differences in PCNA and AgNORs were statistically significant between thymic carcinoma and each of thymoma groups. The overlap of the values between these tumours was minimal in the PCNA stains, although it was considerable in AgNOR counts as previously noted. However, there was no statistically significant difference in these markers between noninvasive and invasive/metastatic thymomas. These results indicate that thymoma in general is a slow-growing tumour compared with thymic carcinoma and that noninvasive thymoma is similar to invasive/metastatic thymoma with regard to proliferative activity; these latter two tumours may represent an essentially identical type in different stages of progression.Part of this work was presented at the 80th General Meeting of the Japanese Society of Pathology held in Osaka, April 1991