Richard Jaworski

The histologic diagnosis of adenocarcinoma in situ and related lesions of the cervix uteri. Adenocarcinoma in situ

Seventy‐two cases of in situ adenocarcinoma (AIS) of the cervix were reviewed. Forty‐five cases had associated cervical intraepithelial neoplasia and 20 cases had changes of wart virus infection. Five cases had associated microinvasive squamous cell carcinoma and one cases showed frankly invasive squamous cell carcinoma (SCC). Of the 72 cases, 41 showed an endocervical type of AIS and three cases an endometrioid type. There was no case of pure intestinal type AIS. Twenty‐eight cases showed a mixed pattern. Architectural patterns characterized by tunnel clusters, cribriform glands, glandular budding and papillary formations were assessed. Most cases showed varying combinations of these patterns but in ten cases significant changes were absent. Both cellular apoptosis and mitotic activity were seen in varying degrees in all cases of AIS. The significance of these and other features of AIS are discussed as well as the conditions involved in the differential diagnosis.

The application of a pCR technique for the detection of immunoglobulin heavy chain gene rearrangements in fresh or paraffin-embedded skin tissue

Summary Although detection of a clonal sequence of the heavy chain gene of immunoglobulin by the polymerase chain reaction (PCR) is frequently used to assess lymphoid infiltrates in skin biopsy specimens, there are no data on the sensitivity and specificity of this test in detecting clonal B cell populations. Having refined a PCR technique for the detection of immunoglobulin heavy chain (IgH) gene rearrangement in both fresh and formalin‐fixed, paraffin‐embedded skin samples, we undertook to define the role of this assay in the diagnostic setting. Thirty‐one cases of cutaneous B cell lymphoma (CBCL), 19 cases of B cell pseudolymphoma (lymphocytoma cutis), 34 cases of benign lymphocytic infiltrates of the skin and one case of cutaneous T cell lymphoma (CTCL) were studied using the polymerase chain reaction assay. All biopsies were formalin‐fixed, paraffin‐embedded skin sections apart from 13 of the 31 CBCL specimens which were fresh skin specimens. DNA from the framework region 3 (FR3) sequence of the IgH genes was amplified to ascertain the presence of a clonal IgH gene rearrangement. The findings were correlated with histological and immunophenotyping results on all samples. The assay performed with 73% sensitivity and 100% specificity, comparable to results obtained examining fresh lymphoid tissue specimens from patients with B cell tumours. The results indicate that this technique is a useful tool in the work up of suspected CBCL and in differentiating between CBCL and mixed lymphocytic infiltrates, a clearly important distinction with regards to prognosis and treatment.

In-situ hybridization using biotinylated DNA probes to human papillomavirus in adenocarcinoma-in-situ and endocervical glandular dysplasia of the uterine cervix

&NA; In‐situ hybridization using biotinylated probes to human papillomavirus (HPV) DNA was performed on formalin fixed paraffin embedded tissue in 30 patients with histologically confirmed adenocarcinoma‐in‐situ (AIS). Thirteen of the 30 cases contained areas of endocervical glandular dysplasia (EGD) admixed with AIS. Twenty one patients showed positive staining of the AIS nuclei for HPV DNA. Ten cases (33%) were positive for HPV 16 DNA and 11 cases (37%) were positive for HPV 18 DNA. No case showed synchronous expression of HPV 16 and 18 DNA. All cases of AIS were negative for HPV 6b and 11 DNA. Four cases of EGD were positive for HPV 18 DNA and 2 cases were positive for HPV 16 DNA. Four of 6 cases of intestinal dysplasia/AIS were positive for HPV 18 DNA. Associated squamous abnormalities (HPV ± CIN ± SCC) were noted in 15 cases. Of these, 7 showed positive staining for HPV DNA in the squamous lesion. Moreover, 5 of these were positive in both the AIS and squamous lesion. In‐situ hybridization using biotinylated DNA probes is a sensitive and safe technique readily adaptable to routine histopathology.

Squamous cell carcinoma in situ arising in inflammatory cloacogenic polyps: report of two cases with PCR analysis for HPV DNA

Summary Inflammatory cloacogenic polyp (ICP) is regarded as part of the spectrum of pathological changes encountered in mucosal prolapse syndrome (MPS)/solitary rectal ulcer. We present the clinicopathological features of two females with squamous cell carcinoma in situ arising in their ICPs. Human papillomavirus (HPV) type 16 was demonstrated in the areas of squamous carcinoma in situ in both polyps by polymerase chain reaction. These cases highlight the need for close scrutiny of the squamous components of these lesions.

Squamous Cell Carcinoma Arising in an Eccrine Hidrocystoma

&NA; This report describes the case of a 63 yr old male with an enlarging lesion on the left cheek. Excision biopsy showed a squamous cell carcinoma arising from an eccrine hidrocystoma. The eccrine hidrocystoma showed foci of squamous metaplasia and the sequence of squamous metaplasia complicated by squamous carcinoma is postulated. Squamous differentiation in eccrine neoplasia is discussed.

Gynandroblastoma of the Ovary

&NA; Gynandroblastoma is an extremely rare primary tumour of the ovary showing morphological evidence of both male and female differentiation. We describe the light and ultrastructural features of this tumour and review the present knowledge about its nature, function and behaviour.

Tumoural calcium pyrophosphate dihydrate crystal deposition disease presenting clinically as a malignant soft tissue mass diagnosed on fine needle aspiration biopsy

Summary Tumoural calcium pyrophosphate dihydrate crystal deposition is a rare manifestation of calcium pyrophosphate deposition disease (CPPD). We present the case of a 75‐year‐old male with a previously resected rectal adenocarcinoma who developed a 5‐cm right‐sided mass at the base of his neck. Clinically and radiologically the lesion was suspicious for malignancy, possibly of metastatic origin. A bedside fine needle aspirate was performed and the smears were mildly cellular showing histiocytes with numerous intracellular and extracellular crystals. These colourless crystals were mostly short and rhomboid shaped and demonstrated weakly positive birefringence. A diagnosis of tumoural CPPD was made. This case is only the second in the English literature diagnosed on fine needle aspiration biopsy. Tumoural CPPD is well known to be a clinical, radiological and occasionally pathological mimic of malignancy. Several cases have been reported where unnecessary radical surgery was performed for this condition. Fine needle aspiration biopsy, as in this case, can provide a rapid and accurate diagnosis of CPPD, avoiding the need for invasive procedures. Polarisation microscopy is a vital adjunct to confirm this diagnosis.

In-situ hybridisation using biotinylated DNA probes to human papillomavirus in adenocarcinoma-in-situ and endocervical glandular dysplasia

DNA in-situ hybridisation using biotinylated probes to Human Papillomavirus DNA (HPV DNA) was performed on 30 patients with adenocarcinoma-in-situ (AIS). 21 patients (70%) showed positive staining for HPV DNA. 10 cases (33%) were positive for HPV 16 DNA and 11 (37%) were positive for HPV 18 DNA. All cases were negative for HPB 6b and 11 DNA. No case showed synchronous staining for HPV 16 and 18 DNA. Thirteen of the 30 cases showed significant areas of endocervical glandular dysplasia (EDG) admixed with AIS. 4 cases of EGD were positive for HPV DNA 18 and 2 cases positive for HPV 16 DNA. These rates are higher than those that have been previously reported. Seven cases showed staining of the associated squamous abnormality (HPV +\- CIN) with HPV DNA probes. Six cases of intestinal dysplasia/AIS were noted. Of these 4 cases were positive for HPB DNA 18. Normal glandular epithelium was always negative for the HPV DNA types examined. This study confirms an association between HPV and the glandular precursors of adeno-carcinoma of the uterine cervix.

Adenocarcinoma-in-situ of the cervix and related lesions

Fifty-two cases of adenocarcinoma in situ (AIS) of the cervix uteri, or lesions closely related to AIS, have been reported by this laboratory over a five-year period. Whereas this lesion has commonly been considered a rare and usually incidental histologic finding, the large majority of these cases involved glandular atypia only and were prospectively diagnosed. Comparison of the findings from this larger series with the 11 cases of AIS described by us previously has led to a shift in emphasis from cell size to sheet architecture as the primary cytologic criterion for diagnosis of this lesion. The structure of AIS sheets was consistent with respect tothe cytologic appearances described here, even when the cells were poorly preserved. Retrospective studies of Papanicolaous smears of other cases from this laboratory that were confirmed histologically as endocervical dysplasia, microinvasive or early invasive adenocarcinoma or deeply invasive adenocarcinoma indicate that these entitites can be distinguished from AIS primarily on the basis of the architecture of the sheets of cells. Cellular groups comprising small, crowded nuclei were a feature of several undercalled deeply invasive adenocarcinomas, and the diagnostic significance of this material is discussed.