The clinical significance of lymph node micrometastasis in stage I and stage II colorectal cancer

AIM: Recent advances in immunohistochemical techniques have made it possible to identify micrometastasis using antibodies to cytokeratins (CK). The aim of the study was to determine the prevalence and prognostic significance of immunohistochemically detected micrometastasis (IHM) in patients with localised colorectal cancer (CRC) (Dukes' A and B). A further aim was to study the prognostic role of histopathological factors such as vascular invasion. METHODS: The original histology of 168 consecutive patients with Dukes' A or B tumours who had undergone curative resection was reviewed. Immunohistochemical staining was performed using CK antibodies, AE1/AE3 and MNF116 on all (n=898) lymph nodes. Survival analysis was performed on 105 cases that had been followed up until death or for at least 5 years. RESULTS: IHM were detected in 17.3% of lymph nodes analysed. Adverse outcome (death/local recurrence) was recorded in 8/49 (16%) patients with IHD-positive nodes and in 10/56 (18%) patients negative for IHM. IHM was not associated with adverse outcome on either univariate (p=0.540) or multivariate analyses (p=0.673). There was no correlation of IHM with age, gender, site, size and grade of tumour, depth of tumour invasion or perineural and vascular invasion. Vascular invasion was the only independent prognostic factor identified. DISCUSSION: We have shown that isolated CK-positive epithelioid cells are commonly found in morphologically benign pericolic lymph nodes of patients with localised (Dukes' A or B) CRC. These cells may represent occult micrometastasis but are not clinically significant. Vascular invasion identifies patients with localised CRC likely to develop recurrences or die of disease (AU)

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Immunohistochemistry increases the accuracy of diagnosis of benign papillary lesions in breast core needle biopsy specimens.

AIMS: Recent studies have suggested that benign papillary lesions without atypia [benign papilloma (BP)] diagnosed on breast core needle biopsy (CNB) may not require excision. However, most have studied only small numbers of cases and scant data are available on the utility of immunohistochemistry in the categorization of papillary lesions on CNB. In the largest published series of BP identified on CNB, we studied the impact of immunohistochemistry on the accuracy of a CNB diagnosis of BP. METHODS AND RESULTS: Breast CNBs (n = 129) with a diagnosis of papillary lesion were immunostained for calponin, p63 and cytokeratin 5/6. Haematoxylin and eosin and immunostained slides were independently reviewed by four breast pathologists. BP was the final excision diagnosis in 35 cases. With the use of immunohistochemistry, the positive predictive value (PPV) of BP diagnosis by the four individual pathologists increased from 72.7-83.3% (mean 79.2%) to 77.8-87.5% (82.1%), the negative predictive value (NPV) increased from 77.8-98.5% (88.6%) to 100% for all four participants and overall accuracy increased from 78.7-92.6% (84.7%) to 90.7-95.4% (92.8%). No case of invasive carcinoma was diagnosed as BP on CNB by any participant. The frequency of ductal carcinoma in situ following a BP diagnosis on CNB ranged from 2.5% to 4.8% (4%) but was only 0-3% (2.3%) after excluding cases that were radiologically suspicious for malignancy. CONCLUSIONS: Immunohistochemistry increases accuracy of BP diagnosis in CNB specimens. Benign papillary lesions diagnosed on CNB do not require excision in the absence of suspicious clinical/radiological findings.

Inhibin is more specific than calretinin as an immunohistochemical marker for differentiating sarcomatoid granulosa cell tumour of the ovary from other spindle cell neoplasms.

AIMS: To describe a case of recurrent sarcomatoid adult granulosa cell tumour (AGCT) of the ovary and to evaluate the usefulness of two ovarian sex cord stromal markers (inhibin and calretinin) in separating sarcomatoid AGCT from true sarcomas. METHODS: A 72 year old woman presented with a recurrent sarcomatoid AGCT in the sigmoid colon mesentery, which histologically mimicked a malignant gastrointestinal stromal tumour (GIST). This index case and 79 sarcomas (32 GISTs, 28 leiomyosarcomas, 15 endometrial stromal sarcomas (ESSs), including one with sex cord-like areas, and four undifferentiated uterine sarcomas) were immunostained using antibodies to inhibin and calretinin. RESULTS: The recurrent sarcomatoid AGCT expressed diffuse, strong cytoplasmic immunoreactivity with inhibin and focal but strong nuclear and cytoplasmic positivity with calretinin. Focal, weak cytoplasmic inhibin expression limited to sex cord-like areas was present in one ESS. None of the other sarcomas expressed inhibin. Focal, strong calretinin immunoreactivity was identified in 11 leiomyosarcomas and one GIST. The case of ESS with sex cord-like areas showed strong immunoreactivity for calretinin limited to the sex cord-like areas. CONCLUSIONS: Inhibin is a useful immunomarker to distinguish sarcomatoid AGCT from other spindle cell neoplasms that may enter into the differential diagnosis. Calretinin appears to be less specific than inhibin.

Absence of group II phospholipase A2, a Paneth cell marker, from the epididymis.

Paneth cell-like metaplasia has been reported in the epithelium of the epididymis and prostatic adenocarcinomas. We studied the expression of group II phospholipase A2 (PLA2), a marker of Paneth cell differentiation, in six orchiectomy specimens with Paneth cell-like metaplasia. Both immunohistochemistry for group II PLA2 protein and in situ hybridization for the mRNA of group II PLA2 gave negative results in all six cases but positive reaction for lysozyme. The results show that the cells of the Paneth cell-like metaplasia are not true Paneth cells.

Histologic variations in the epididymis: findings in 167 orchiectomy specimens.

Nonpathologic morphologic variations in the epididymal histology in 167 orchiectomy specimens were analyzed to assess and document the nature, frequency, and possible relation to patient age and underlying testicular pathology. Variations in histology included intranuclear eosinophilic inclusions, lipofuscin pigment, cribriform hyperplasia, Paneth cell-like metaplasia, and nuclear atypia. Intranuclear eosinophilic inclusions were observed in 72.5% of patients, and they appeared to occur at an older age than cribriform hyperplasia and Paneth cell-like metaplasia. Lipofuscin pigment was found in 32.9% of patients; this change was observed predominantly in ductuli efferentes and was more commonly associated with obstructive changes. Cribriform hyperplasia was seen in 41.9% of patients, and it occurred in 1 normal testis and in 33 testes with diverse pathologic alterations. Paneth cell-like metaplasia characterized by bright eosinophilic intracytoplasmic hyaline-like granules and globules, was present in 8.3% of patients and was accompanied by changes of obstruction in almost all instances. The globules were strongly periodic acid-Schiff positive, both before and after diastase digestion, and were negative for chromogranin A, KP-1, and MAC387 immunostains. Nuclear atypia, similar to that seen in seminal vesicles, was focally present in 13.8% of patients and tended to occur at an older age. The authors conclude that variations in epididymal morphology are fairly common and, therefore, surgical pathologists should be aware of these changes. Although exuberant in some patients, in no cases did these variations cause serious diagnostic problems.

Transferrin receptor expression by blast cells in acute lymphoblastic leukemia correlates with white cell count & immunophenotype.

Transferrin receptor (TR) expression by blast cells in 127 cases of acute lymphoblastic leukemia (ALL) at presentation and 19 cases at relapse was examined using three anti-TR monoclonal antibodies to find its correlation with prognostic features such as the total leucocyte count (TLC), the morphology of blast cells and their cytochemical and immunophenotypic properties, as well as age and sex of the patients. Blasts in 62 per cent of thymic (T) ALL cases at presentation showed significant TR expression as compared to only 10.9 per cent in common ALL (CALL) (P < 0.001). This differential expression of TR was also observed among cases with > 50 x 10(9)/l TLC, while in cases with < 50 x 10(9)/ l TLC no such pattern was observed (30% TR positivity in T-ALL vs 20% TR positivity in non-T-ALL). Furthermore, the percentage of TR positive blasts was significantly higher (P < 0.005) in cases with > 50 x 10(9)/l TLC as compared to those with < 50 x 10(9)/l (48.3-54.4% vs 24.9-28.8%). In contrast to CALL cases at presentation, those at relapse showed a very high TR positivity (54-66%), similar to the T-ALL cases (53-84%). This suggests a high proliferative rate of blast cells in ALL at relapse, irrespective of its immunophenotype. There was no correlation of TR expression with blast cell morphology (FAB L1 vs L2), their cytochemical properties and sex of the patients. However, a significantly higher incidence of TR positivity was observed in patients above 10 yr of age compared to those below 10 yr (47% vs 15%; P < 0.001). The incidence of T-ALL was also significantly higher in the former group (56%) compared to the latter (33%) (P < 0.005). Our data suggest that by virtue of its association with features of poor prognosis, e.g., age above 10 yr, expression of thymic markers, high leucocyte count and disease relapse, TR expression by blast cells in ALL could serve as a biological marker of poor prognosis.

Correlation of transferrin receptor expression with histologic grade and immunophenotype in chronic lymphocytic leukemia and non-Hodgkin's lymphoma.

The neoplastic lymphoid cells in 33 patients with chronic lymphocytic leukemia (CLL), 1 case of prolymphocytic leukemia (PLL), and 29 patients with various types of non-Hodgkin's lymphoma (NHL) were examined for the expression of transferrin receptors (TR) using a panel of three anti-TR monoclonal antibodies (MAb). Both immunofluorescence and immunoperoxidase techniques were applied in each case. All cases of B-CLL (31) were negative for TR expression, while both the cases of T-CLL, and the only case of T-PLL showed significant TR-positive cell populations. Similarly, all 13 cases of "low-grade" NHL were TR negative, while 6 of 7 cases of "high-grade" lymphomas (lymphoblastic and immunoblastic) had up to 28% TR-positive cells. A proportion (4/9) of "intermediate grade" lymphomas had 10-15% TR positivity. Interestingly, the majority of B-leukemia/lymphoma (49/55) cases were TR negative, while all 8 cases of T-cell leukemia/lymphoma were TR positive. This clearcut association of TR expression with high-risk morphologic and immunophenotypic subgroups of lymphoid leukemia/lymphoma points to the potential role of TR as a prognostic marker in lymphoproliferative disorders.