Extramammary Paget's disease of the penis is associated with long-standing transitional cell carcinoma and radiotherapy.
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Biomedical subjects
Publications and source records attributed to J M Theaker.
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AIMS: To determine the applicability of rapid, sequence specific polymerase chain reaction (PCR)-based HLA class II genotyping for the distinction of complete from partial hydatidiform moles (HM) using DNA extracted from formalin fixed and paraffin wax embedded tissue. METHODS: Nine HM were studied. DNA was extracted from formalin fixed and paraffin wax embedded tissue after mechanical separation of decidual and molar components. HLA class II DRB (DRB1, -3, -4, and -5) and DQB1 genotyping was performed using a parallel series of PCR reactions, each of which contained sequence specific primers designed to amplify different HLA DRB and DQB1 alleles or allele groups (PCR-SSP analysis). In each case the HLA DRB and DQB1 genotypes identified within the decidua and HM were compared. RESULTS: Within the decidual tissue, HLA DRB genotypes were assignable in all nine cases, and HLA DQB1 genotypes were identified in seven cases. Within the molar tissue, HLA DRB genotypes were assignable in seven cases, and at least one HLA DQB1 allele was identified in seven cases. Interpretation based on HLA class II genotyping was therefore possible in two cases classified on histological appearances as complete HM, in four classified as partial HM, and in one HM of uncertain type. Different HLA DRB and DQB1 haplotypes were identified within the decidual and molar tissue from both complete HM, consistent with a solely paternal origin and supporting the histological diagnosis. HLA DRB and DQB1 alleles common to the decidual and molar tissue were present within the four partial HM and the HM of histologically uncertain type, consistent with combined maternal and paternal genetic input to these HM, supporting the histological diagnosis in four cases and suggesting that the histologically equivocal case was also a partial HM. CONCLUSION: PCR-SSP HLA class II DRB and DQB1 typing is reliably applicable to DNA extracted from formalin fixed and paraffin wax embedded tissue. Therefore, in a suitably equipped HLA typing laboratory, this technique provides a useful adjunct to histological examination for differentiation of complete from partial HM.
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Mislabelling of surgical specimens can seriously affect the accuracy of histopathology reports. We describe two cases in which clinically suspected mislabelling was investigated by polymerase chain reaction (PCR)-based HLA DRB and DQB tissue typing of paraffin biopsy-derived DNA, using sequence specific primers (PCR-SSP HLA typing). In the first case, two patients underwent surgery for breast carcinoma. A subcutaneous lymph node containing metastatic carcinoma was received with the breast specimen from one patient, but was clinically considered more likely to originate from the other patient who underwent breast surgery on the same day. In the second case, histological examination of retained products of conception from a young woman revealed adenocarcinoma, but a repeat curettage specimen consisted of secretory phase endometrium. In case 1, PCR-SSP HLA typing confirmed the clinical suspicion that the subcutaneous lymph node received with tissue from one patient originated from the other patient. This result converted the first patient from lymph node positive breast carcinoma to lymph node negative disease. In case 2, there was no evidence from PCR-SSP HLA typing that the endometrial samples had originated from different patients. PCR-SSP HLA typing requires fewer steps than methods based on PCR amplification followed by oligonucleotide probing (PCR-SSOP HLA typing), and relies on the amplification of shorter sequences of DNA. Therefore, this technique can produce more rapid results than PCR-SSOP HLA typing, and is ideally suited to typing partially degraded DNA derived from formalin-fixed and paraffin-embedded tissue.
Sections from 95 skin lesions excised at pigmented lesion clinics in England and Scotland were studied by eight histopathologists in order to evaluate consistency in the use of histopathological terms for features of diagnostic and prognostic importance for cutaneous malignant melanoma. The level of agreement (kappa) amongst the panel improved after discussion and re-definement of criteria for several features. These included, architectural and nuclear atypia, pagetoid infiltration and radial and vertical growth phases. A high level of agreement was achieved for an overall benign or malignant diagnosis (kappa = 0.77) but use of more specific terms such as benign naevi with atypia and melanoma < or = 0.76 mm thickness, was associated with only an intermediate level of agreement. Of the original diagnosis of melanoma, 17% were re-classified by the panel as benign with atypia and 2% reported to be benign were judged to be melanoma. This reflected the high proportion of borderline lesions in the study. The use of standardized diagnostic criteria with precise definitions has been shown to improve consistency in diagnosis and it is recommended for general application. From this should emanate more reliable incidence figures for thin melanoma, and improved understanding of the nature of these early lesions, to the benefit of patient and clinician alike. The poor concordance in distinguishing severe dysplasia in the junctional component of melanocyte proliferations from melanoma in situ and superficial dermal invasion improved only modestly despite intensive efforts. Since melanoma in situ and severe dysplasia cannot be distinguished by objective measurements and since their clinical management is the same, the panel suggests that attempts to separate them in diagnostic reports should be discontinued and they could both be referred to as melanocytic intraepidermal neoplasia (MIN). If it becomes accepted that dermal invasion without a vertical growth component can also be managed identically to MIN, then this invasive radial phase may be appropriately referred to as microinvasion and linked to MIN for the purposes of clinical management.
AIMS: To immunophenotype and quantitate glomerular and interstitial inflammatory cells in cases of idiopathic membranous and IgA glomerulopathy; to correlate cell numbers with aspects of clinical data and renal function. METHODS: Routine indirect immunoperoxidase staining was performed on frozen section renal biopsy specimens for T and B lymphocyte related antigens, macrophages and MHC class II antigens. Double immunohistochemical staining was performed to identify CD45RO+ and CD45RA+ cells. RESULTS: In IgA glomerulopathy correlations were found relating interstitial cell numbers to creatinine concentration at biopsy (CD45RO+ and CD45RA+ cells) and follow up creatinine concentration (CD3+, CD4+, CD8+, CD45RO+, and CD45RA+ cells). Also in IgA glomerulopathy mean arterial pressure at biopsy correlated with interstitial cell numbers and most recent follow up creatinine concentration. There were no correlations between glomerular inflammatory cells and renal function in either disease. Double staining showed that although most glomerular CD45RO+ and CD45RA+ cells were macrophages, positive cells in the interstitium were lymphocytes. The interstitial CD45RO+:RA+ ratio in normal renal biopsy specimens was approximately 5:1; for IgA glomerulopathy it was 1.5 and was 1.0 in idiopathic membranous glomerulopathy. CONCLUSIONS: This study demonstrates that interstitial, and not glomerular, inflammatory cell numbers correlate with renal function in primary glomerular disease and that double staining is necessary to interpret positive immunostaining for antigens located on more than one type of inflammatory cell. Detailed investigation of the interstitial CD45RO+ and CD45RA+ cells may give an insight into the pathogenesis of glomerular disease.
AIMS: To alert pathologists to the spectrum of histological appearances that may be seen in injection site reactions related to aluminium. METHODS: Four cases of injection site reaction were examined microscopically using routine staining with haematoxylin and eosin, electron microscopy and by electron probe microanalysis. RESULTS: As in previous reports, all four cases included collections of histiocytes which contained faint granular brownish refractile material within their cytoplasm; ultrastructural examination showed this to be aluminium. Two cases showed a prominent inflammatory reaction with numerous lymphoid follicles and a notable eosinophilic infiltrate. Two cases showed unusual features not described previously. In one, there was a sclerosing lipogranuloma-like reaction with unlined cystic spaces containing crystalline material. The other case presented as a large symptomatic subcutaneous swelling which microscopically showed diffuse and wide-spread involvement of the subcutis by a lymphoid infiltrate with prominent lymphoid follicles. CONCLUSIONS: This report highlights the changes encountered in aluminium injection site reactions and emphasises that the lesions have a wider range of histological appearances than described previously.
PURPOSE: Despite its histologically benign appearance, primary pure teratoma of the testis is believed to have metastatic potential and behave similarly to other nonseminomatous germ cell tumors. We present our experience with the natural history and management of pure teratoma. MATERIALS AND METHODS: We reviewed the histological findings and clinical history of 15 patients with primary pure teratoma who were treated during a 15-year period, accounting for 4.2% of all nonseminomatous germ cell tumors treated during the same period. Fourteen patients were available for followup and are included in this report. RESULTS: In 8 patients the tumor was composed entirely of mature teratoma and in 6 immature elements were also present, although this finding was not associated with an increased frequency of metastatic disease. Carcinoma in situ was found adjacent to the tumor in 12 cases. Of 10 patients with stage I disease at presentation who were entered on a surveillance program only 2 have had relapse. The remaining 4 patients had metastatic disease at presentation and, thus, metastatic disease occurred in a total of 6 of the 14 patients (43%) with a median followup of 46 months (range 5 to 197). Metastatic disease was confined to the retroperitoneum in all 6 patients and only 2 patients had elevated serum marker levels. Five patients were treated with primary chemotherapy followed by resection of a residual mass and in all cases teratoma was identified in the resected mass. One patient underwent surgical excision of a retroperitoneal mass, which contained teratoma and yolk sac tumor, followed by chemotherapy. All patients are alive without evidence of progressive disease. CONCLUSIONS: In patients with primary pure teratoma of the testis metastatic disease may develop and the metastases may contain other subtypes of nonseminomatous germ cell tumors in addition to teratoma. There is probably a reduced frequency of relapse, which should be considered when advising patients with stage I disease, but otherwise management should be the same as for other testicular nonseminomatous germ cell tumors and the prognosis should be excellent.
BACKGROUND: A small proportion of patients with testicular germ cell tumors present with widely metastatic disease and are treated initially with chemotherapy. Little is known about the efficacy of systemic chemotherapy in eradicating the primary testicular germ cell cancer; however, there is concern that the testis may act as a sanctuary site for germ cell cancer in these patients, and orchiectomy, is, therefore, recommended after chemotherapy. METHODS: The results from a clinical and pathologic review of 24 patients who underwent delayed orchiectomy after chemotherapy are presented. The testicular pathologic findings are correlated with those in extragonadal masses and also with a blinded review of postchemotherapy testicular ultrasound scans. RESULTS: The most common testicular pathological finding was a dense fibrous scar that was found in all patients. Three patients had persistent testicular germ cell cancer, six had mature teratoma, and one had carcinoma in situ. There was a strong concordance between the major testicular pathologic findings and those in the resected extragonadal masses. All three patients with persistent testicular germ cell cancer subsequently had disease progression in the extragonadal sites. Testicular ultrasound examination did not distinguish accurately between residual tumor or scar in the testis. CONCLUSION: Persistence of the primary testicular germ cell cancer is most likely due to the same heterogeneous response to chemotherapy observed in different metastatic sites. Because current imaging techniques cannot identify accurately those patients with residual testicular germ cell cancer or related testicular abnormalities that may predispose to subsequent relapse, orchiectomy after chemotherapy remains appropriate.
Eleven cases of chrysiasis have been studied ultrastructurally and by electron probe microanalysis. Tissue samples were examined both with and without osmium and uranyl acetate staining. There was a significant morphological difference in the appearance of the gold deposits within aurosomes between the two groups. The untreated group showed finely granular deposits, often arranged in a linear fashion. Aurosomes from samples treated with osmium and uranyl acetate showed more electron-dense deposits and star-like formations. We propose that treatment of the tissue with osmium and uranyl acetate causes a change in the electron microscopic appearance of aurosomes, including the formation of the characteristic star-like aurosomes.
Eight patients are described who had palpable breast lumps with clinical and imaging features suspicious of malignancy which proved to be sclerosing lymphocytic lobulitis on histological examination. In this series the typical mammographic appearance of this condition was increased parenchymal density and/or localized stromal distortion while on ultrasound, the typical appearance was an ill-defined mass with distal acoustic shadowing. This rare benign condition has been described in association with longstanding insulin-dependent diabetes or autoimmune disease, but four of our eight patients had no such medical history.
Two cases of combined goblet cell carcinoid and mucinous cystadenoma occurring in the appendix are reported. The histogenesis of the goblet cell carcinoid remains one of its most controversial aspects and the occurrence of both of these relatively uncommon tumours in the same organ may lend support to the unitary stem cell hypothesis on the origin of this tumour. Alternatively, this occurrence may represent an example of the adenoma/carcinoma sequence.
This study evaluates the use of human leukocyte antigen (HLA) class II PCR-SSO typing for the investigation of suspected specimen contamination in four routine surgical histopathology cases. Two cases were of patients undergoing transurethral resection of the prostate gland. The third case was a patient undergoing excision of a subcutaneous small cell carcinoma. The fourth case was a patient undergoing reversal of a Hartman's procedure for adenocarcinoma of the colon. Tissue was extracted from routinely processed formalin-fixed, paraffin-embedded material and HLA class II typed, using a non-radioactive polymerase chain reaction-sequence specific oligonucleotide probe technique (PCR-SSO), using probes specific for the DRB, DQA, and DQB loci. The accuracy of PCR-SSO typing of DNA extracted from paraffin biopsy material was confirmed by concordant results for DRB, DQA, and DQB typing in five separate control individuals from whom frozen and paraffin lymph node biopsies were available. PCR-SSO typing was also successful in the four study cases and revealed that contamination had occurred in two cases, eliminating this possibility in the remaining cases. This study demonstrates that DNA can be reliably amplified and accurately typed from routinely processed material, and reveals a useful new application for PCR-SSO tissue typing.
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Germ cell neoplasia of the testis can spread into the rete testis in a pagetoid manner, but this is less often recognized than vascular invasion or direct spread into the tunica albuginea. The rete testis was studied in 71 orchidectomy specimens: 47 with an untreated germ cell tumour, 18 with germ cell neoplasia after treatment with chemotherapy, and six with other tumours. Pagetoid spread into the rete testis was seen in 14 of the 47 cases of germ cell tumour. The cytology of the infiltrating cells was that of intratubular germ cell neoplasia. Hyperplasia of the rete testis was seen in six cases. In three of the four testes with untreated germ cell neoplasia and hyperplasia of the rete, neoplastic cells were seen in the hyperplastic rete epithelium. The two testes with extensive pagetoid involvement of the rete testis by intratubular germ cell neoplasia both had associated hyperplasia of the rete testis. Two of the 18 testes with germ cell neoplasia after chemotherapy had focal hyperplasia. Pagetoid involvement of the rete testis by intratubular germ cell neoplasia is common and may be a cause of hyperplasia of the rete testis.
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Chrysiasis, the systemic deposition of gold pigment in patients on long term chrysotherapy, is identified histologically as small black granules within macrophages. Histological sections from 12 confirmed cases of chrysiasis were examined under crossed polarized light. This revealed a striking orange-red birefringence of the pigment not detected in other histologically similar deposits. This technique provides a valuable adjunct to the histological identification of gold without the need to resort to ultrastructural and analytical procedures.