Periorbital erythema and swelling as a presenting sign of lupus erythematosus in tertiary referral centers and literature review.

Background Cutaneous lupus erythematosus (CLE) includes a broad range of dermatologic manifestations. Periorbital involvement, however, is a relatively rare clinical presentation of CLE. Objectives This clinical study aimed to investigate the characteristics of this unique presentation of CLE in tertiary medical centers. Methods We enrolled patients with periorbital erythema and swelling as the presenting sign of lupus erythematosus, from January 2003 to November 2017, using the data of 553 pathologically proven CLE cases from the registration database of the Chang Gung Memorial Hospitals in Taiwan. Results We enrolled a total of 25 patients. The mean age was 46.7 years and 68% of the patients were female. Most of the patients (84.0%) presented with unilateral involvement, with the left orbit involved in 15 patients (60%); the upper eyelid was the most frequently involved (72%). Mean duration between the onset of clinical manifestations and the diagnosis of CLE was approximately 59 weeks. Nineteen patients had been previously misdiagnosed. All patients had features compatible with CLE on histopathological examination. In contrast, laboratory analysis of the autoimmune profile often revealed negative results, including those for antinuclear antibodies (25%). Notably, anti-SSA/SSB (45.5%) showed the highest positive rate. During follow-up, six patients developed systemic lupus erythematosus (SLE) and two patients developed Sjögren syndrome. Conclusions The diagnosis of CLE presenting as periorbital erythema and swelling is often delayed because of clinical mimicry and the high proportion of negative results on autoantibody tests. Increased clinical suspicion and prompt histopathological examination are crucial for early diagnosis. Moreover, one-fourth of the patients ultimately developed SLE, which highlights the importance of clinical awareness.

Histopathological analysis and clinical correlation of drug reaction with eosinophilia and systemic symptoms (DRESS).

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe cutaneous adverse drug reaction. However, its histopathological features have not been well defined. OBJECTIVES: To identify the clinicohistopathological findings of DRESS, and analyse the cutaneous histopathological changes observed in DRESS compared with those observed in maculopapular exanthema (MPE). METHODS: In a retrospective study, conducted at Chang Gung Memorial Hospital (Taiwan) between 2001 and 2011, we compared the clinicohistopathological features of 32 patients with probable/definite DRESS (defined by the RegiSCAR scoring system) with those of 17 patients with MPE. RESULTS: The major pathological changes observed in patients with DRESS included dyskeratosis (97%), epidermal spongiosis (78%), interface vacuolization (91%), perivascular lymphocytic infiltration (97%) and eosinophilic infiltration (72%). Many pathological features were common to both MPE and DRESS. However, severe dyskeratosis, epidermal spongiosis and severe interface vacuolization were significantly more prominent in cases of DRESS (P < 0·05). The presence of severe dyskeratosis was significantly associated with the clinical severity of renal impairment (P = 0·01). CONCLUSIONS: The severe dyskeratosis detected in patients with DRESS may correlate with a greater extent of systemic involvement compared with that noted in MPE. However, the histopathological changes associated with DRESS are not entirely specific.

The PTPN22gain-of-function+1858T(+) genotypes correlate with low IL-2 expression in thymomas and predispose to myasthenia gravis.

Protein tyrosine phosphatase, non-receptor type 22 (PTPN22) inhibits T-cell activation and interleukin-2 (IL-2) production. The PTPN22(gain-of-function)+1858T(+) genotypes predispose to multiple autoimmune diseases, including early-onset (non-thymomatous) myasthenia gravis (MG). The disease association and the requirement of IL-2/IL-2 receptor signaling for intrathymic, negative T-cell selection have suggested that these genotypes may weaken T-cell receptor (TCR) signaling and impair the deletion of autoreactive T cells. Evidence for this hypothesis is missing. Thymoma-associated MG, which depends on intratumorous generation and export of mature autoreactive CD4(+) T cells, is a model of autoimmunity because of central tolerance failure. Here, we analyzed the PTPN22 +1858C/T single nucleotide polymorphism in 426 German Caucasian individuals, including 125 thymoma patients (79 with MG), and investigated intratumorous IL-2 expression levels. Unlike two previous studies on French and Swedish patients, we found strong association of PTPN22 +1858T(+) genotypes not only with early-onset MG (P=0.00034) but also with thymoma-associated MG (P=0.0028). IL-2 expression in thymomas with PTPN22 +1858T(+) genotypes (P=0.028) was lower, implying weaker TCR signaling. We conclude that the PTPN22(gain-of-function) variant biases towards MG in a subgroup of thymoma patients possibly by impeding central tolerance induction.

Clinicopathological features and prognosis of drug rash with eosinophilia and systemic symptoms: a study of 30 cases in Taiwan.

BACKGROUND: Drug rash with eosinophilia and systemic symptoms (DRESS), a group of non-blistering severe cutaneous adverse drug reactions (SCADRs), is characterized by skin rash and multiorgan involvement. Details of this reaction have not been reported in the literature so far. AIM: We investigate clinical and pathological features and prognosis of DRESS and hope this study will provide data concerning this disorder in Taiwan. METHODS: From January 2001 to June 2006, a total of 30 patients, diagnosed with DRESS, were enrolled and evaluated for demographic characteristics, pathological findings, complications and outcome. RESULTS: Patient ages ranged from 13 to 78, with an equal sex ratio. The most common offending drug was allopurinol followed by carbamazepine. Pathologic changes observed were lichenoid dermatitis, erythema multiforme, pseudolymphoma and vasculitis. Impairment of liver and renal functions and blood dyscrasia were frequent complications. Active infection or reactivation of HHV-6 was observed in 7 of 11 patients studied serologically. Two patients developed type 1 diabetes mellitus. The mortality rate was 10% (3 of 30). CONCLUSIONS: DRESS is a heterogeneous group of life-threatening conditions. The leading drug in DRESS in Taiwan is allopurinol. High eosinophil count and multiple underlying diseases are poor prognostic factors in patients with DRESS.

Corpuscular thymoma: entity or variant of organotypical thymomas WHO B2/B3?

Hassall's corpuscles are regular structures in the medulla of the normal thymus and in non-neoplastic thymic conditions, e.g. in multilocular thymic cysts. In thymomas, however, they are inconsistently found, and are believed to indicate medullary differentiation of WHO type B1-3 thymomas. We present five organotypical thymomas resembling WHO type B2 and B3 thymomas, but with an abundance of Hassall's corpuscles. We wonder whether this exceedingly rare observation might herald a distinct entity. Four tumors were asymptomatic, incidental findings and of low Masaoka stage (I or II) [20] . One patient suffered from myasthenia gravis which disappeared upon surgical removal of the thymus, while all other patients had no concomitant autoimmune disease. Two patients had a relapse-free follow-up of 12 and 2 years, respectively, upon curative surgery, and another tumor was an autopsy finding; follow-up data of two more recent cases was not yet available. The neoplastic epithelium other than Hassall's corpuscles was arranged either in a cortical type B2 pattern or in type B3 solid cords. In all examples, there was cyst formation, inflammatory reaction and repair, indicative of a long-standing condition. Immature T cells were present in all instances. "Corpuscular thymomas" morphologically resemble WHO type B2 and B3 thymomas, but appear biologically indolent and are rarely associated with myasthenia gravis. Whether they qualify for a separate entity has to be proven by larger series, including genetic studies.

Single-stranded DNA binding protein from bacteriophage cf: characterization, gene localization and protein-ssDNA complex.

The single-stranded DNA binding protein from the filamentous bacteriophage cf has been purified and characterized. The first 12 amino acids, resulting from the N-terminal amino acid sequencing analysis of the protein, agree with an open reading frame (ORF) on the cf genome. The ORF contains 294 bp and codes for a 98 a.a. protein of molecular weight 10.8 kDa, consistent with the result from the denaturing protein gel analysis. The protein appears to be a homodimer as evident from the apparent molecular weight of about 22 kDa obtained from native protein gel analysis. The gene location of the protein has been identified as gene V of the cf single stranded genome, same as that from the M13 phage. The GVP of cf shows a strong sequence homology to the ssDNA binding proteins of Ff, IKe and Pf3 filamentous phages. The DNA binding wing of GVP, conserved among the filamentous phages, has been predicted for cf. To further characterize the protein, the GVP-ssDNA complex of cf has been purified from the infected host (Xanthomonas campestris pv. citri) by density gradient centrifugation. Transmission electron microscopy (TEM) images of the complex showed that it is about 1200 nm in length and 9 nm in diameter and it has a highly regular morphology with a central groove shadow running along the entire structure, but without any apparent helical pattern seen in the M13 complex. The GVP-ssDNA complex of cf seems more rigid than that of M13. Our computer modeling study suggested that this difference between the two complexes may be due to the additional 11 or 12 amino acids at the C-terminal end of the cf-GVP.

Primary small-intestinal lymphomas in Taiwan: immunoproliferative small-intestinal disease and nonimmunoproliferative small-intestinal disease.

PURPOSE: The clinicopathologic findings in 45 adult Chinese patients with primary small-intestinal lymphoma (PSIL) are described and compared with those in Western countries and in underdeveloped nations. The efficacy of combination chemotherapy is also assessed. PATIENTS AND METHOD: Six patients had immunoproliferative small-intestinal disease (IPSID) indicated by the presence of alpha-heavy chain protein (alpha-CP) in body fluids or tumor tissues. Thirty-nine patients had non-IPSID, including one with postrenal transplant lymphoma. Thirty-three non-IPSID patients received a minimum of four cycles of combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP). RESULTS: All IPSID patients presented with the clinical and laboratory features of severe intestinal malabsorption, and all had diffuse lymphoplasmacytic infiltration in the mucosa of the small bowel. Lymphomas were localized mainly in the jejunum and mesenteric nodes. The histologic subtypes were diffuse large cell in two, immunoblastic in three, and diffuse mixed in one. All patients responded poorly to chemotherapy, with a median survival duration of 10.5 months. The common presenting symptoms of the 39 non-IPSID patients included abdominal pain (90%), weight loss (31%), abdominal mass (26%), obstruction (26%), and perforation (23%). Diffuse large-cell and immunoblastic lymphomas constituted 82% of cases. Four patients had stage IE, 19 stage II 1E, and 16 stage 112E disease according to the Musshoff's criteria; 22 had bulky tumors and 19 had multiple tumors. The tumors were completely resected in 14 patients. Of 33 patients treated with combination chemotherapy, 73% achieved a complete remission. With a median follow-up duration of 90 months, there have been four relapses, with only one at the primary tumor site. The overall 5-year survival and disease-free survival rates for non-IPSID patients who were treated with chemotherapy were 59% and 54%, respectively. CONCLUSION: Intensive chemotherapy produces long-term disease-free survival in locally advanced non-IPSID PSIL.

The primary immunity determinant in modulating the lysogenic immunity of the filamentous bacteriophage cf.

Bacteriophage cf is the first single-stranded DNA phage that has been shown to set up a stable lysogenic state with its genome integrated into the host chromosome. From the isolation and characterization of a virulent mutant, cf-tv2, we report the first investigation into the mechanisms of the immunity established by the filamentous bacteriophage. The mutation in cf-tv2 enables the phage to produce plaques on lawns of cf lysogenic cells. The mutation was defined as a 49-nucleotide deletion located in a 0.59 kb NcoI/KpnI fragment of cf replicative form DNA. Two messages, cM1 and cM2, transcribed from the immunity region of wild-type cf but in opposite directions, were detected. In cf-tv2, the 49-nucleotide deletion abolishes cM2 transcription. The primer extension assay suggests a possible RNA-RNA interaction directed by base-pairing of the cM1 and cM2 RNAs. A frameshift mutation of the open reading frame ORF 165, encoded by cM2, resulted in a 10(5) plating efficiency on the cf lysogen. These observations suggest that both RNA-RNA interaction and repressor protein inhibition are involved in the mechanism of cf immunity. A model is proposed for the regulation of cf immunity.

Role of anisotropy in determining the selective action of antiarrhythmics in atrial flutter in the dog.

OBJECTIVE: The aim was to clarify the electrophysiological and anatomical features of the preferential site of action of antiarrhythmic drugs in the re-entrant circuit of canine atrial flutter. METHODS: Electrophysiological and anatomical findings were correlated in 17 anaesthetised adult mongrel dogs with atrial flutter associated with an intercaval anatomical obstacle, before and after intravenous administration of disopyramide (2 mg.kg-1) and flecainide (2 mg.kg-1). RESULTS: Before drug injection, a rate dependent prolongation of conduction time occurred in the low right atrium where the conduction was slow during atrial flutter. Disopyramide (n = 8 dogs) and flecainide (n = 9 dogs) terminated atrial flutter, with conduction block occurring in this slow conduction area in the low right atrium. Although the degree of drug induced prolongation of refractoriness in this particular area was similar to those in other areas of the right atrium, conduction was depressed to a greater extent in this region. Anatomical study revealed that a thick pectinate muscle that branched from the crista or crista terminalis itself ran perpendicular to the wavefront of the pacing impulse and atrial flutter in this slow conduction area. CONCLUSIONS: These data indicated that slow conduction might be attributed, at least in part, to anisotropic conduction over the thick muscle bundle in the low right atrium, and that antiarrhythmic drugs preferentially produced conduction block in this area. Anisotropic conduction in the low right arium is an anatomical substrate for slow conduction in the re-entrant circuit and for the site preference of antiarrhythmic drugs in the present canine model.

Characterization of an open reading frame involved in site-specific integration of filamentous phage Cf1t from Xanthomonas campestris pv. citri.

Cf1t is a single-stranded DNA filamentous phage; a 1.9-kb segment of DNA from Cf1t was found to be responsible for site-specific integration into Xanthomonas campestris pv. citri (XW47), in the absence of any Xanthomonas origin of replication. Deletion analysis and introduction of amber stop codons into this fragment from Cf1t revealed an open reading frame (ORF344) which was involved in the integration function. The predicted amino-acid sequence of ORF344 bears no homology with conserved sequences of the integrase family.

Kikuchi's disease (histiocytic necrotizing lymphadenitis). A clinicopathologic study of 79 cases with an analysis of histologic subtypes, immunohistology, and DNA ploidy.

We conducted a clinicopathologic study of 79 cases of Kikuchi's disease. Our results confirmed that Kikuchi's disease is a distinctive type of necrotizing lymphadenitis that affects primarily the cervical lymph nodes of young adults and has a self-limited clinical course. However, female predominance was not as striking as heretofore reported. A low, but possible, recurrence rate of 3.3% was documented. Extranodal cutaneous involvement occurred in one patient who had a more severe and protracted clinical course. Classification of the histopathologic changes into three histologic types was proposed: proliferative, necrotizing, and xanthomatous types. These three types differed in certain aspects of their clinical features. Immunohistologic analysis revealed that the predominant cells of the lesions were various types of histiocytes, including the enigmatic plasmacytoid monocytes. A variable number of CD8(+) T cells correlating with the duration of the disease was detected. B cells were nearly absent, and only an insignificant number of OPD4(+) T cells was present. Eight cases studied by the flow cytometric DNA analysis all showed a diploid DNA content. Although the histologic changes of Kikuchi's disease were variable, the findings were sufficiently distinctive to permit accurate diagnosis. Malignant lymphoma and especially lupus lymphadenitis can be mistaken for Kikuchi's disease; thus differentiation is crucial.

Cutaneous manifestation of Kikuchi's histiocytic necrotizing lymphadenitis.

A young man who presented with cervical Kikuchi's histiocytic necrotizing lymphadenitis later developed a cutaneous plaque lesion. Histologic study of the cutaneous lesion revealed dermal patchy infiltrates composed of large lymphoreticular cells and scattered cells resembling Hodgkin or Reed-Sternberg cells. This condition was initially mistaken for a large-cell lymphoma. But it was later discovered that the dermal cellular infiltrates were similar to that of the involved lymph node. Many of the large cells in the infiltrates were found to be histiocytes. Immunohistochemical study revealed that the cells resembling Hodgkin or Reed-Sternberg cells were activated fibroblasts. The presence of foamy histiocytes and the absence of neutrophils in the skin lesions were also similar to the involved lymph node. Cutaneous Kikuchi's disease may be mistaken for cutaneous lymphoma. Cutaneous involvement by Kikuchi's disease may also denote a worse clinical course.

Mucicarminophilic histiocytosis. A polyvinylpyrrolidone (PVP) storage disease simulating signet-ring cell carcinoma.

In Taiwan, a peculiar type of cell with mucicarmine-positive bubbly or vacuolated cytoplasm was sporadically observed in a variety of surgical specimens removed for neoplastic or non-neoplastic conditions. They closely mimicked signet-ring cell carcinoma. Study of 14 such cases and review of the related literature led to the conclusion that the peculiar cells were storage histiocytes containing polyvinylpyrrolidone (PVP). Because they were shown to be mucicarmine-positive, we designated them " mucicarminophilic histiocytes." Particulate bodies sometimes observed in association with mucicarminophilic histiocytes were believed to be the extracellular counterpart of the cytoplasmic vacuoles. Our survey also revealed that PVP-containing intravenous injection fluids had been used in Taiwan as recently as 5 years ago. For surgical pathologists, PVP-containing mucicarminophilic histiocytes should not be mistaken for signet-ring cell carcinoma or signet-ring cell lymphoma. Mucicarminophilic histiocytes can be identified by the positive mucicarmine, colloidal iron, Gomori methenamine silver, Congo red, Sudan black B, Fontana-Masson argentaffin, and Victoria blue; but negative periodic acid-Schiff, alcian blue, and Giemsa stains.

Thymic carcinoma arising in thymoma is associated with alterations in immunohistochemical profile.

Thymic carcinoma is an uncommon tumor. Most cases appear to arise de novo, but in rare instances they can arise in thymomas. We report the clinicopathologic features and immunohistochemical profile of five cases of thymic carcinoma accompanied by a component of thymoma. Immunohistochemical studies were performed with the avidin-biotin-peroxidase complex method using monoclonal antibodies to p53(DO7), CD99(O13), epithelial membrane antigen, CD5(NCL-CD5-4C7), vimentin (V9), and cytokeratins 7, 8, 18, and 19. The patients consisted of three men and two women with a median age of 57 years. One patient had myasthenia gravis, and the other four presented with chest symptoms. One patient had concurrent adenocarcinoma of the lung with metastasis. Four of the patients died within 15 months. The thymomas consisted of two large polygonal cell thymomas, two squamoid thymomas, and one spindle cell thymoma. The malignant components included two undifferentiated carcinomas, one spindle cell carcinoma, one squamous cell carcinoma, and one clear cell carcinoma with squamous differentiation. There was no correlation between the histologic types of the thymoma and the thymic carcinoma. In three cases, excluding the two squamoid thymomas, the thymic carcinomas occurred in the necrotic areas of the thymoma. They showed upregulated expression of epithelial membrane antigen and cytokeratins 7, 8, 18, and 19, similar to the so-called "interface phenomenon" described in the invasion front of other types of carcinoma. Increased p53 protein expression was observed in all five carcinomas, and there was loss of CD99+ immature T lymphocytes. Among the thymic carcinomas, only the squamous component of the clear-cell carcinoma stained for CD5, a marker commonly expressed in thymic carcinomas. Paradoxically, a squamoid thymoma, but not its associated spindle cell carcinoma, expressed CD5, suggesting the acquisition of an "aggressive" phenotype by the squamoid thymoma, but with loss of the marker on malignant transformation. One undifferentiated carcinoma acquired vimentin immunoreactivity, whereas four other carcinomas and all five thymomas were negative. In conclusion, thymic carcinoma can arise in any histologic type of thymoma, including spindle cell thymoma, which is generally regarded as a benign neoplasm. The prognosis appears to be poor. Tumor necrosis in a thymoma should alert the pathologist to search for malignant change. The malignant change is commonly associated with increased expression of epithelial membrane antigen, cytokeratin subtypes, or p53 protein, and loss of CD99+ immature T lymphocytes, and is occasionally associated with a change in the expression of CD5 or vimentin.

Clear cell papulosis of the skin. A new entity with histogenetic implications for cutaneous Paget's disease.

A new skin condition characterized by multiple white papular eruptions was observed in two young brothers. Histologic study revealed many benign pagetoid clear cells in the basal layer of the acanthotic epidermis with decreased pigmentation. These cells contained cytoplasmic mucin and were positive for keratin AE1/AE3, carcinoembryonic antigen, and epithelial membrane antigen. The staining pattern was identical to that of extramammary Paget's disease. The presence of mucin granules and cytoplasmic filaments corresponding to AE1/AE3 were confirmed ultrastructurally. Comparative histochemical and immunohistochemical studies with normal eccrine sweat glands, Toker's nipple clear cells, and Paget cells of mammary and extramammary Paget's disease suggest that these clear cells are an aberrant derivative of sweat-gland epithelial cells in the epidermis. AE1/AE3 is an excellent marker for the "clear cells" of both the condition described and the cells in the nipple. The term "clear cell papulosis" is proposed for this new entity. The clear cell identified provides evidence for the existence of potential precursor cells in the epidermis for cutaneous Paget's disease.

Keloidal dermatofibroma: report of 10 cases of a new variant.

Dermatofibroma is a common cutaneous tumor. Unusual variants of dermatofibroma that exhibit various epidermal changes or different cellular composition have been described. We observed 10 cases of a novel variant of dermatofibroma characterized by keloidal change within the tumor. Formalin-fixed, paraffin-embedded tissues were used for histochemical and immunohistochemical studies. The patients consisted of six women and four men; median age was 34 years (17 to 59 years). All tumors occurred on the extremities, and six were present for at least 2 years. Tenderness was mentioned in four cases. They were described as erythematous or brown papules 1 cm or smaller. Clinical appearance did not deviate from that of ordinary dermatofibromas. Microscopically, the excised tumors showed a superficial circumscribed area of keloidal change under an atrophic epidermis in an otherwise ordinary dermatofibroma. In the keloidlike area, multinucleated giant cells, hemorrhage, hemosiderin deposits, and scattered KiM1P-positive histiocytes, but not factor XIIIa-positive or CD34-positive cells were present among the thick collagen fibers. There were no known recurrences. This variant dermatofibroma should not be overlooked as a simple keloidal scar. The observation of keloidal change in dermatofibromas may support the connotation that trauma is a possible cause of dermatofibroma. The fact that Asian people are more prone to develop keloid may have led us to find this new variant.

Kimura's disease. Involvement of regional lymph nodes and distinction from angiolymphoid hyperplasia with eosinophilia.

The clinicopathologic features of nine patients with Kimura's disease and 15 patients with angiolymphoid hyperplasia with eosinophilia (ALHE) were studied and compared in order to clarify the confusion between these two entities. The common features shared by both conditions included male predominance, predilection for the head and neck regions, tendency to recur, and vascular nature of the lesion with lymphoid and eosinophilic infiltrates. However, Kimura's disease was usually seen in younger individuals for a longer duration and occurred as a deeply seated, large soft-tissue mass, without significant change of the overlying skin initially. In addition, it was often accompanied by peripheral blood eosinophilia and elevated serum IgE. In contrast, ALHE lesions were multiple small dermal papular or nodular eruptions observed in older patients and present for a shorter duration; they were less frequently accompanied by peripheral blood eosinophilia. The main histopathological difference was the presence of "histiocytoid" or "epithelioid" blood vessels in ALHE but not in Kimura's disease. Kimura's disease was further characterized by eosinophilic folliculolysis; IgE deposits in the germinal centers; and frequent involvement of regional lymph nodes, salivary glands, and skeletal muscles. The eosinophilic infiltration, especially the formation of eosinophilic microabscesses, along with increased number of small blood vessels, perinodal eosinophilic infiltration, and eosinophilic folliculolysis characterized the nodal involvement by Kimura's disease. Our study indicates that Kimura's disease and ALHE are two distinct clinicopathologic entities. We place particular emphasis on the involvement of regional lymph nodes in Kimura's disease. In addition, we observed Charcot-Leyden crystals and polykaryocytes in both conditions. One of the patients with Kimura's disease also had an associated nephrotic syndrome.

Mesonephroid blastoma. A previously undescribed renal tumor of childhood.

We describe a renal tumor arising in a 4 1/2-year-old boy and characterized by the formation of epithelial tubules in a primitive mesenchymal stroma. We call attention to certain unique structural features of this tumor, which set it apart from Wilms' tumor. The tissue components regularly observed in Wilms' tumor were absent from the primary neoplasm despite exhaustive search, suggesting that this case should be considered distinct from nephroblastoma. However, a metastasis appeared that was formed entirely by undifferentiated nephrogenic cells. Based on structural appearance, histogenesis from mesonephros is tentatively proposed. No precedent was found in the literature of a tumor of this description.

Thymic carcinomas: histopathological varieties and immunohistochemical study.

Thirteen cases of primary thymic carcinomas are described. The patients' ages ranged from 19 to 64 years, with a median of 40 years. Nine of them were male. Chest pain with or without cough was the main presenting symptom. No patient had myasthenia gravis. Five histological types were identified; two were undifferentiated (lymphoepithelioma-like) carcinoma, one was a clear-cell carcinoma, two were mixed squamous and small-cell carcinoma, and six were squamous cell carcinoma. All the tumors were variably positive for anti-keratin antibody AE1 and AE3, but negative for AE2. Anti-neuron specific enolase antibody was useful in identifying and confirming the small-cell carcinoma component of the mixed carcinomas. Anti-epithelial membrane antigen antibody aided in revealing the glandular structures in mixed adenosquamous and small-cell carcinomas. Thymic carcinomas were histopathologically differentiated from thymomas by their malignant cytological appearance, increased mitotic activity, and central tumor necrosis. All six patients with pure squamous-cell carcinoma were still alive, with a median survival time of 27 months. All but one of the other patients of different histological types died, the exception being a recent case of mixed adenosquamous and small-cell carcinoma; their median survival was 19.5 months, or 18 months when the latter surviving case is included. The prognosis of patients with pure squamous-cell carcinoma was better.