Maria Elena Errico

Loss of oestrogen receptor β, high PCNA and p53 expression and aneuploidy as markers of worse prognosis in ovarian granulosa cell tumours

Aims:  Ovarian granulosa cell tumour (OGCT) is a sex‐cord stromal tumour with a general trend toward late relapse and/or metastasis. However, mortality rate corrected for long‐term follow‐up shows that about 50% of patients die within 20 years of diagnosis. Classical clinicopathological parameters are unable to predict the biological behaviour of OGCT. The involvement of a recently characterized subtype of oestrogen receptor, ERβ, in ovarian carcinogenesis has been hypothesized.

Epithelioid sarcoma: report of two cases diagnosed by fine-needle aspiration biopsy with immunocytochemical correlation.

Epithelioid sarcoma (ES) is an aggressive soft‐tissue malignant tumor generally arising in the distal extremities of young adults. The microscopic diagnosis of ES is often difficult because of its rarity and its possible confusion with other malignant tumors or even with benign granulomatous processes. Two cases of ES and a recurrence of one of these tumors, diagnosed by fine‐needle aspiration biopsy (FNAB), are reported. Cytologic smears were quite similar in both cases including the relapse, showing single or loosely arranged groups of medium to large atypical cells. Single cells had well‐defined eosinophilic cytoplasms and one or more atypical, eccentrically located nuclei, resulting in a plasmacytoid appearance. Nuclei had fine granular chromatin and one or two large nucleoli. The cells sometimes palisaded along the edges of necrotic material. The immunocytochemical stains showed diffuse cytoplasmic positivity for cytokeratins (CAM 5.2) and both cytoplasmic and cell membrane positivity for vimentin, while S‐100 protein and HMB 45 immunostaining were negative, thus supporting the cytological diagnosis of ES, which was subsequently proven on the surgical samples. Diagn. Cytopathol. 1999;21:405–408.

DNA ploidy and cyclin D1 expression in basal cell carcinoma of the head and neck.

Basal cell carcinomas (BCCs) may be subdivided into primary with a favorable biologic course (BCC1) and recurrent and/or metastatic (BCC2). No clear association between primary tumor location, histologic subtype, or other clinicopathologic variables and predisposition for BCC2 has been found. Histopathologic criteria are limited for prognostication. To identify prognostic factors useful for planning therapy, we studied cyclin D1 immunohistochemical expression, DNA ploidy, and epiluminescence light microscopic (ELM) patterns in 60 cases of BCC (30 BCC1 and 30 BCC2) in the head and neck region, half of which were hyperpigmented. Cyclin D1 was absent in 27 cases, expressed at low level in 4 cases, and overexpressed in 30 cases. Seven BCCs were euploid, 28 exhibited a mixed cellular population, and 25 were aneuploid. Among aneuploid tumors, hypodiploidy was found in 12. Among the 30 pigmented carcinomas, only 15 showed a typical ELM pattern. No association between pigmentation and more aggressive biologic behavior of BCC was found. These results and follow-up data seem to indicate that an unfavorable outcome can be predicted by hyperexpression of cyclin D1, aneuploidy, and an atypical ELM pattern for pigmented cases. A definite hypodiploid peak was associated with worse prognosis. The analysis of cyclin D1 expression and DNA ploidy may help identify BCC with an aggressive phenotype and a poor clinical outcome.

Symptomatic epidural compression in infants with neuroblastoma: a single-center experience with 5 cases.

Infants affected by neuroblastoma with symptomatic epidural compression require early diagnosis and appropriate treatment to avoid severe late complications. However, no established guidelines are available regarding the optimal treatment of these patients. We describe 5 such infants. The interval between the onset of symptoms and tumor diagnosis was 3 to 8 days in 4/5 cases. None developed paraplegia before or after treatment. Treatment for epidural compression included first-line laminoplasty followed by chemotherapy in 3 patients, and chemotherapy first in the remaining 2. To date, all are alive and none have developed severe complications after a follow-up of 9 to 39 months (median, 20).

Melanocytic tumors of uncertain malignant potential in childhood: do we really need sentinel node biopsy?

To the Editor We are intrigued by the report of Abraham et al.1 illustrating the case of a 4-year-old child with a histomorphologically atypical, but genetically normal (by array comparative genomic hybridization) melanocytic neoplasm, with deep penetrating nevus (DPN)-like features. In a sentinel lymph node biopsy (SLNB), there were foci of tumor, which the authors considered as an evidence of a ‘metastatic’ melanocytic tumor, of uncertain malignant potential (MelTUMP). Interestingly, the very same case was interpreted by McCalmont and Bastian2 in a ‘counter perspective’ as representing an ‘unconventional’ DPN with microscopic involvement of the SLNB. The issue raised in the aforementioned papers concerns the biological significance of tumor deposits in SLNB from an ambiguous primary tumor. In our opinion, it is important to remember that the specific clinical setting in which the issue is raised is childhood. We do believe that childhood melanoma does exist, and that its clinicopathologic features are peculiar enough to justify its classification as an entity, distinct from the ‘conventional’ histotypes of melanoma. However, if cases of clear-cut melanoma are excluded from prognostic evaluation, one can immediately realize that a truly unfavorable behavior (i.e. distant metastases and/or disease-related death) is highly uncommon in atypical melanocytic tumors of the childhood. In the study by Cerroni et al.3 on 57 MelTUMP, there were 26 cases with unfavorable outcomes; of which, only three cases were diagnosed in patients younger than 10; and of these, two had been included as ‘unfavorable’ because of a massive replacement of the sentinel lymph node. However, the patients were still alive with no evidence of disease. Therefore, even massive replacement of a sentinel lymph node does not necessarily imply an ominous prognosis. In addition, and not surprisingly to us, Cerrato et al.4 have described a completely favorable clinical outcome in 24 cases of atypical Spitz tumor diagnosed at a mean age of 9 years, and treated with simple excision without SLNB. Similarly, Mills et al.5 have reported no unfavorable outcome in 24 patients, 5 of whom were less than 10 years of age, in spite of a 29% rate of positivity of SLNB. In our view, these cases represent the best proof that true metastatic disease from MelTUMP in childhood is highly unlikely to occur. Figure 1 shows a case with a highly worrisome clinical picture. The patient was a 3-year-old girl, who underwent excision of a 5-mm pigmented lesion of the right auricle. Histopathologically, the lesion disclosed the features of an ambiguous melanocytic neoplasm, that we interpreted as an epithelioid blue nevus/pigmented epithelioid melanocytoma. Besides its own provisional classification into an ‘intermediate’ category between nevus and melanoma, the lesion itself had no relevant feature of histopathologic atypia: pigment distribution was symmetric (Fig. 1A); the neoplasm respected the adnexa (Fig. 1A) and the epidermis (Fig. 1B); epithelioid and dendritic melanocytes were strongly prevailing over melanophages and showed no necrosis and inflammation; mitotic figures were not found, even after ‘bleaching’ of the tissue sections, and after an immunostain with the anti Ki67 antibody. No lymph vessel permeation was found; clinically, however, bluish pigment lines were seen to be confluent in a ‘Y’ fashion, at

Application of Plastic Embedding to Fine Needle Aspiration Biopsy

OBJECTIVE To explore the possible advantages that plastic embedding offers to fine needle aspiration biopsy (FNAB). STUDY DESIGN A series of 54 FNABs was fixed in Kryofix (30 cases) and acetone (24 cases), plastic embedded and cut using a rotative microtome. The 2-micron sections obtained were May-Grünwald-Giemsa and Papanicolaou stain in all cases; mucicarmine, Alcian Blue, periodic acid-Schiff (PAS), PAS-diastase and Feulgen stain for DNA cytometric evaluation were also applied in five cases. Immunocytochemical staining using the antibodies cytokeratin 1-8, epithelial membrane antigen, vimentin, Ki-67, lysozime, calcitonin and carcinoembryonic antigen was carried out with the immunoalkaline phosphatase method. RESULTS The fragments in the sections were perfectly two dimensional; the architectural features of the original tissues were preserved. Morphologic details of nuclear membranes, nucleoli and mitotic figures were excellent. Cytochemical and immunocytochemical stains were successful in all cases. Immunostains showed the precise location of the signal (nuclear, nucleolar or cytoplasmic), a clear background and preservation of morphology. CONCLUSION Plastic embedding can be applied to FNAB to solve the problem of dense cellular groups, to study structural and cellular details, and to capitalize on the diagnostic material available for serial cytochemical, quantitative and immunocytochemical purposes.

Skin Adnexal Tumours: A Large Spectrum of Clinic-Pathological Lesions

Skin adnexal neoplasms comprise a wide spectrum of more than 80 benign and malignant tumours, exhibiting morphological differentiation towards pilosebaceous unit, eccrine and apocrine glands. In addition more than one line of differentiation in this neoplasm could be observed. These tumours generally exhibit a benign behaviour, but malignant histotypes also exist. Clinical diagnosis of specific entity and of their potential malignancy is quite impossible. Thus, the diagnosis always requires surgical excision of skin lesion, and histological features at haematoxylin and eosin-stained sections are considered generally adequate for the correct classification of skin adnexal tumours. The use of histochemical and immunohistochemical stains could further aid in this purpose. Finally, they are usually encountered as single, sporadic tumours, but they may also occasionally be multiple and hereditary, heralding complex genetic syndromes that comprise visceral cancers.