Validation of mitosis counting by automated phosphohistone H3 (PHH3) digital image analysis in a breast carcinoma tissue microarray.

Mitosis counting in H&E stained sections is the most informative constituent of the Nottingham histological grade in breast carcinoma prognosis. Phosphohistone H3 (PHH3) immunohistochemistry (IHC) is a highly specific marker of mitoses, with practical application in identifying mitoses in poorly fixed or distorted tissue and is of prognostic significance in breast carcinoma. Our aim was to assess methods of PHH3 IHC mitosis counting in a tissue microarray (TMA) of 2 mm cores from 36 resected breast carcinomas. Mitoses in H&E and PHH3 stained slides were manually scored by pathologist consensus and expressed as counts/2 mm. PHH3 stained cores were also evaluated by automated digital image analysis (DIA). Results were compared using Spearman correlation. A strong and significant correlation was observed between manual PHH3 and manual H&E mitotic counts (correlation = 0.81; p < 0.0001) and between automated PHH3 DIA and manual H&E mitotic counts (correlation = 0.79; p < 0.0001). More mitoses were identified with PHH3 IHC than with H&E. Manual and DIA PHH3 counts were strongly and significantly correlated (correlation = 0.83; p < 0.0001) and of similar absolute values. PHH3 DIA is a valid alternative to manual counting with potential application in breast cancer reporting and prognostication.

Handling of radioactive seed localisation breast specimens in the histopathology laboratory: the Western Australian experience.

Radio-guided occult lesion localisation using iodine-125 seeds (ROLLIS) is a novel method of localisation for impalpable in situ and invasive carcinomas that has been the subject of a recent pilot study and pilot study extension in Western Australia. Robust protocols for radiation safety, specimen labelling, specimen tracking, seed retrieval and seed disposal were developed at two Western Australian laboratories to minimise the risk of seed loss. The processes are safe and effective with no significant radiation exposure to pathologists and with acquisition of all seeds intact and undamaged. The success can be attributed to developing specific seed retrieval techniques, suited to local preferences at each institution, with input from surgeons, radiologists and medical physics personnel. These techniques are now routine and will continue in the randomised control phase of the ROLLIS study.

Diagnosis of breast microcalcifications: a comparison of stereotactic FNA and core imprint cytology as adjuncts to core biopsy.

Stereotactic core biopsy (CB) using 14-gauge needles was adopted as the standard method of diagnosis of screen-detected breast microcalcifications (MC) at Sir Charles Gairdner Hospital in 1996. Fine needle aspiration (SFNA) was included as an adjunct, to optimise sensitivity and to provide immediate reporting. Recently, core imprint cytology (CI) has been shown to have a high sensitivity in diagnosing malignancy. The aims of this paper were to evaluate the accuracy of SFNA as an adjunct to CB, and whether CI could replace SFNA for immediate reporting in MC. Part A is a retrospective review of CB/SFNA of screen-detected MC from May 1998 to February 2000. A minimum of five cores was performed. SFNA samples were restricted to a maximum of three needle passes. Part B is a prospective study of CI from May to November 2000. In Part A, there were 406 MC in 353 women and 81 carcinomas were proven on excision. The complete sensitivity of CB for a diagnosis of malignancy was 97.5% and of SFNA was 65%. No false-positive diagnoses were made by either method. No extra carcinomas were detected using SFNA. In Part B, CB/CI were performed on 203 MC from 165 women. There were 38 carcinomas and 30 of these (79%) were diagnosed as malignant on CI. No false-positive diagnoses were made. The predictive value of a benign diagnosis was 95%. SFNA had little value as an adjunct to core biopsy in MC. CI promises to be useful in providing same day diagnosis for counselling purposes and for planning future surgery.

Can CD34 discriminate between benign and malignant hepatocytic lesions in fine-needle aspirates and thin core biopsies?

BACKGROUND: Distinguishing well differentiated hepatocellular carcinoma (HCC) from benign hepatocellular lesions is a well recognized problem in fine-needle aspiration (FNA) cytology. The endothelial cell marker CD34 is negative in normal hepatic sinusoids and stains vessels diffusely in HCC. This feature is useful in distinguishing benign from malignant hepatocytic lesions in histological specimens, although benign lesions may show focal positivity for CD34 confined to periportal and periseptal areas. In this study, we assess the role of CD34 in cell block and thin core biopsy material from benign and malignant hepatocellular lesions, and compare it with reticulin staining. METHODS: Cell blocks and thin core biopsies were assessed from 40 cases of HCC and 25 benign hepatocytic lesions. HCCs were scored for nuclear grade. Sections were stained for CD34 antigen and scored semi-quantitatively. Previously performed reticulin stains were reviewed. RESULTS: Thirty three of 40 HCCs (82.5%) showed diffuse positivity for CD34. The other seven cases showed either focal positivity (four cases), minimal positivity (two cases) or negative staining (one case). These results did not correlate with the nuclear grade of the tumor. Two of 25 benign cases (8%) showed diffuse positivity for CD34, 8 showed focal positivity, 11 showed minimal positivity, and 4 showed negative staining. All HCCs showed an abnormal reticulin pattern characterized by expanded trabeculae and islands, or sheets, with decreased or absent reticulin. All of the benign hepatocellular lesions showed a normal trabecular reticulin pattern. CONCLUSIONS: Diffusely positive CD34 staining is useful to support a diagnosis of well differentiated HCC, but in our study the reticulin stain distinguished more consistently between benign and malignant lesions.

Cytodiagnosis of well differentiated hepatocellular carcinoma: can indeterminate diagnoses be reduced?

BACKGROUND: Distinction of well differentiated hepatocellular carcinoma (HCC) from benign hepatocellular lesions is a well recognized problem in fine-needle aspiration (FNA) cytology, sometimes leading to indeterminate reports. The aim of this study was to critically examine criteria that might allow definitive diagnosis in these cases. METHODS: FNA smears and cell blocks from 65 patients with primary hepatocellular lesions were reviewed. Seventy separate samples had been obtained. The initial reports in these samples were: HCC in 34, benign findings in 27, and indeterminate findings in 9. We defined architectural and cytological features seen in the malignant cases but not seen in the benign cases, including an assessment of reticulin in cell blocks. These criteria were then applied to the indeterminate cases. RESULTS: The most specific cytologic criteria of malignancy in well differentiated HCC were (i) numerous stripped atypical nuclei, (ii) macronucleoli, (iii) increased mitoses, and (iv) multinucleation. The most specific architectural criteria in smears were (i) widened trabeculae, (ii) well defined capillaries traversing tissue fragments, and (iii) solid islands of hepatocytes rimmed by endothelial cells. The most valuable architectural criteria in cell blocks were (i) trabeculae greater than two cells thick and (ii) reduced or absent reticulin framework. Using the above criteria a retrospective diagnosis of HCC was possible in eight of the nine indeterminate cases, all but one of which have subsequently been confirmed as malignant. CONCLUSIONS: Close attention to architectural features in both smears and cell blocks should allow most well differentiated HCCs to be diagnosed by FNA cytology. A reticulin stain should be part of the routine assessment of cell blocks. Cancer (Cancer Cytopathol)

Medullary carcinoma of the thyroid: accuracy of diagnosis of fine-needle aspiration cytology.

BACKGROUND: A preoperative diagnosis of medullary carcinoma of the thyroid (MCT) allows for the investigation of associated multiple endocrine neoplasia/ pheochromocytoma, and definitive surgery without the need for frozen section. Criteria for cytodiagnosis are well known but variable patterns of presentation may cause diagnostic difficulty. METHODS: This study examines the accuracy of cytodiagnosis and the value of ancillary tests in 17 patients seen between 1976 and 1997. Nine patients underwent thyroid gland aspirations, five patients underwent fine-needle aspiration (FNA) of the thyroid and cervical lymph nodes, and three patients underwent cervical lymph node aspiration alone. Electron microscopy (EM) of aspirated material was performed in nine cases and immunocytochemistry in two cases. RESULTS: In all cases the diagnosis was suggested by FNA. In four cases, diagnosis and management were based on cytology alone. EM of FNA material was confirmatory in nine cases, two of which also showed positive calcitonin immunocytochemistry. In three cases the diagnosis was not proven until surgical resection, and in one case FNA confirmed lymph node metastasis in known MCT. Frozen section in five patients did not change the level of diagnostic confidence over the FNA diagnosis in any case. In four other thyroid tumors (one Hürthle cell follicular carcinoma, two anaplastic carcinomas, and one hyperplastic nodule) MCT was suspected in the FNA differential diagnosis but later excluded. In the Hürthle cell tumor immunoperoxidase staining was positive for calcitonin and in one anaplastic carcinoma, a neuroendocrine phenotype was suggested. In the latter case, additional EM excluded MCT. CONCLUSIONS: Although correct diagnosis is made by cytology in the majority of instances, other tumors may show cytologic findings similar to MCT. EM of FNA material was found to be the most definitive method of proving or excluding MCT. Immunocytochemistry may be misleading for rarely performed tests.

Salivary monomorphic adenomas of dermal analogue type: report of two cases.

Two cases of monomorphic adenoma, dermal analogue type, are presented illustrating fine-needle aspiration cytology and subsequent histopathology. Aspiration findings were similar in both cases, demonstrating aggregates of mildly disorganised small regular epithelial cells bordered by a thick rim of basement membrane material. In the first case seen, there was a prominent lymphoid component which gave rise to the false suspicion that the lesion was lymphoepithelial in nature. The cytological features of this tumour are characteristic, however, and their recognition is important to enable distinction from malignancy (e.g., adenoid cystic carcinoma), other benign neoplasms (e.g., plemorphic adenoma), and non-neoplastic conditions.

Carcinoma cuniculatum of the abdominal wall.

A case of carcinoma cuniculatum (verrucous carcinoma of the skin) is reported. The 15 X 16 cm tumour was located on the abdominal wall. We believe this to be the first reported case of carcinoma cuniculatum occurring on the abdominal wall.

A control, double-blind comparison of mepivacaine injection versus saline injection for myofascial pain.

In a double-blind study 28 patients with acute, localised muscle pain received four local injections of mepivacaine 0.5%, and 25 patients with the same type of pain received local injections of an equivalent volume of physiological saline. The group receiving saline tended to have more relief of pain, especially after the first injection. The results thus show that pain relief is not due merely to the local anaesthetic. The study therefore raises questions about the mechanism by which local injections into muscle relieves pain, since there is the possibility that a similar effect might also be achieved by merely inserting a needle into the trigger point. Physiological saline is considered to be a more appropriate fluid for injection therapy than local anaesthetics since it is less likely to produce side-effects.