Histological identification

Histological identification of the malignant nature is the critical issue; some lesions escape the criteria mentioned previously. Examples are:

♦ Small-sized renal cell carcinomas (erroneously called adenomas because of their size).

♦ Highly differentiated 'lipoma-like' liposarcomas.

♦ Controversial pigmented skin lesions ('dysplastic' naevi).

♦ Questionable soft tissue tumours—such as atypical fibro-histiocytoma, fibromatosis, haemangiopericytoma; myelodysplasia.

While lesion classification uncertainty has decreased in recent years, 'borderline' ovarian tumours are still controversial; for some time they were classified as (cyst)adenocarcinomas of low malignant potential, but now as (cyst)adenomas with uncertain malignant potential or atypical proliferating tumours.

Lesions preceding malignant tumours are as various as the natural histories of the subsequent cancers. At some sites (e.g. uterine cervix and prostate) pre-malignant lesions may persist for a long time, others are short-lived. Among the former, some lesions permit reproducible histological typing and even grading, whereas ductal carcinoma in situ of the breast can be sub-typed and graded according to cell differentiation. At other sites the current criteria allow only a reproducible overall diagnosis of carcinoma in situ. Examples include:

♦ Most organs lined by squamous epithelium (skin, upper respiratory and alimentary tract).

♦ Transitional epithelium (lower urinary tract).

Melanoma in situ is recognized as a stage in melanoma tumour progression. 'Dysplasia', though vague, is nonetheless well established and employed to define pre-malignant changes of, for example, larynx, uterine cervix, and Barrett's oesophagus.

Malignant potential without well-defined or reproducible histopathological features is attributable to hypercellular leiomyomas of the uterus, hyperplasia of plasma cells in the bone marrow accompanied by monoclonal gammopathy, nodular hyperplasia of regenerating cirrhotic liver, dysplastic naevi with random atypia, large congenital cutaneous naevi, and lymphomatoid granulomatosis.

Although clonality is a basic feature of malignancy in early phases of proliferation before multiple subclones develop due to additional mutational events (genetic instability), it is not a synonym of malignancy as shown by the curable, occasionally self-limited, local lesions of Langerhans' cell histiocytosis (eosinophilic granuloma) whose monoclonality was recently proven.

Epithelial tumours comprise over 80% of neoplasms; adenoma being the most common epithelial benign growth and carcinoma the general term for the malignant counterpart. The latter may be additionally classified according to:

♦ Origin (adenocarcinoma, Merkel-cell ca.).

♦ Extracellular matrix (desmoplastic ca.).

♦ Cellular content (glycogen-rich ca., lipid-rich ca.).

♦ Cell products (mucinous ca., keratinizing ca.).

The proliferating cell type is recalled in the names of tumours of soft parts and of myoid origin, both benign and malignant (e.g. fibroma vs. fibrosarcoma, leiomyoma vs. leiomyosarcoma). Most of the latter are subject to grading, and several systems have been proposed.

The central nervous system (CNS) displays an array of cell types from which several tumours may arise (astrocytes, ependymal cells, neuroblasts, etc.). A few CNS tumours are histologically benign (gangliocytoma, central neurocytoma); all others show a broad range of grades of malignancy. Progression from low to high-grade malignancy is a common event.

Mixed benign epithelial-stromal tumours are common in salivary glands (pleomorphic adenoma) and breast (fibroadenoma). Despite phenotypic multi-cellularity, clonality was recently proven for these tumours, supporting a totipotential stem-cell divergence hypothesis. Developmental errors are probably responsible for teratomas, which mostly arise along the midline of the body and in the gonads—these commonly display immature and malignant features in the testes and mature benign features in the ovaries.

Tumour-like conditions are non-neoplastic lesions that mimic neoplastic growth. Their importance lies in the differential diagnostic work-up. Chronic reactive inflammatory response may produce deceptively neoplastic-looking lesions such as nodular fasciitis of soft tissue. Other common lesions which simulate a neoplasm indicate:

♦ Aneurysmal bone cysts.

♦ Traumatic neuromas.

♦ Intravascular papillary endothelial hyperplasia.

♦ Central giant-cell granuloma of bone.

♦ Reactive hyperplastic nodules of mesothelium.

Tumour-like conditions also include hamartomas (e.g. pulmonary and hepatic bile duct)—local circumscribed developmental errors— and choristomas which are aggregates of ectopic tissue (e.g. nasal glial heterotopia, accessory spleen).

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