Histochemistry: historical development and current use in pathology.

We describe the history of the histochemical stains that contributed most to the development of modern pathology during the last two centuries. Histochemical stains are presented in a list, which provides the essential information about year, country and main use of each to enable the reader to follow the chronological and geographical history of histochemistry. In addition to the historical evaluation of histochemistry development, we investigate how many classical histochemical stains survive in a modern laboratory of pathology and how often they are used for diagnostic practice compared to immunohistochemical (IHC) techniques. A ratio of about one histochemical reaction to 13 IHC reactions was tabulated. Finally, our data make it possible to define different cultural approaches to the terminology of histochemical and IHC stains: the former were based on eponyms, which link the stain with the name of its inventor, while the latter use a more impersonal biological terminology.

'Indeterminate for malignancy' (Tir3/Thy3 in the Italian and British systems for classification) thyroid fine needle aspiration (FNA) cytology reporting: morphological criteria and clinical impact.

BACKGROUND: The British system (Thy1-5), the Bethesda system for reporting thyroid cytopathology (BSRTC) and the Italian Society of Anatomic Pathology and Cytology (SIAPEC) classification represent the most important international classifications for thyroid cytopathology. Irrespective of the system used, the 'indeterminate' categories are still debated among cytopathologists, particularly with regard to diagnostic criteria, clinical impact of subclassification and role of molecular techniques. AIM: We aimed to find answers to the following questions: Are there shared criteria in cytological preparations that allow the division of indeterminate follicular lesions into subcategories? What is the true clinical impact of this possible subclassification? METHODS: Among 1150 consecutive thyroid fine needle aspiration (FNA) specimens, 80 patients had nodules with a final cytological report of Tir3 (SIAPEC)/Thy3. These 80 cases were re-evaluated and subclassified according to morphological criteria into three groups: pure follicular proliferations, Hürthle cell follicular lesions and atypical proliferations. RESULTS: Sixteen (20%) cases were categorized as pure follicular proliferations, 40 (50%) as Hürthle cell follicular lesions and 24 (30%) as atypical proliferations. Surgery was performed in 57 cases (71%). Cyto-histological correlation showed that follicular adenoma was the most frequent final diagnosis in the cases treated by surgery (24/57, 42%). The overall malignancy rate in the Tir3 category was 28% (16/57). Atypical proliferations were more often malignant than either of the follicular groups (53% versus 19%, P = 0.019). CONCLUSIONS: A five-tiered classification, subdividing the 'indeterminate for malignancy' class into 'follicular proliferations' and 'atypical lesions' could be adopted. As a result of their higher risk of malignancy, surgical management of the atypical lesions would be justified. In future, the introduction of a genetic panel might contribute to their stratification, to the determination of a more accurate risk of malignancy of the atypical lesions and to the verification of follicular proliferations that are benign.

A case of carcinoid of Meckel's diverticulum associated with gastric adenocarcinoma.

Meckel's diverticulum is an uncommon gastrointestinal congenital anomaly that occurs in 1-3% of the population. It is sometimes associated with complications related to the presence of ectopic tissue (obstruction, ulceration, hemmorhage, inflammation, perforation, fistula and tumors). Neoplastic degeneration of Meckel's diverticulum mucosa is rare, developing in only 1-5% of all diverticula, usually asymptomatic and occasionally discovered. Disease is metastatic, usually to the liver, in 25% of cases. We report a case of asymptomatic unsuspected carcinoid of Meckel's diverticulum with ileal, hepatic and mesenteric metastasis discovered during a gastrectomy performed for gastric adenocarcinoma. The patient underwent ileal and Meckel diverticulum resection, excision of mesenterial metastasis and liver bisegmentectomy. Furthermore, total gastrectomy with esophago-jejunal anastomosis was performed. After an 18-month follow-up period, the patient is alive and disease free. Owing to possible neoplastic degeneration, Meckel's diverticulum should be resected when occasionally discovered. In the presence of a carcinoid tumor, even if associated with metastatic disease, extended resection is recommended.

Carcinosarcoma of the parotid gland: cytological, clinicopathological and immunohistochemical study of a case.

Manifesting a putative origin from a pleomorphic adenoma, carcinosarcoma of the salivary gland is a heterologous neoplasm in which a sarcomatous and a carcinomatous component coexist. We present a parotid gland carcinosarcoma in a 77-year-old man with peculiar morphological findings. Fine-needle aspiration cytology allowed a preoperative diagnosis of poorly differentiated carcinoma. At histologic examination, the tumor showed biphasic differentiation with an epithelial component made up of well-differentiated keratinizing squamous carcinoma and ductal-type adenocarcinoma, and a mesenchymal component, revealing focal areas of osteosarcoma and myoepithelial malignant proliferation. Carcinosarcoma is a very rare malignant neoplasm, accounting for 0.16% of malignant salivary gland tumors: only 60 cases have been reported, some of which arose "de novo", i.e., without clinico-pathologic evidence of a pre- or co-existing pleomorphic adenoma.

Unusual recurrence of cervical adenosquamous carcinoma after conservative surgery.

The use of less radical procedures for the treatment of early cervical cancers is gaining interest among physicians and young patients. Some authors have described surgical procedures aimed at reducing the surgical aggressiveness but the safety of such procedures remains debated. After a polypectomy, a young patient had a diagnosis of stage Ia(2) cervical adenosquamous carcinoma in 1995. As she wished to preserve her fertility, she underwent a cone biopsy and pelvic lymphadenectomy, without evidence of tumor spread. In 1998, at the 13th week of gestation, she had a diagnosis of a pelvic mass. The mass was a recurrence of carcinoma involving the myometrium, just underneath the peritoneum. She underwent a radical hysterectomy with bilateral oophorectomy. An ovarian metastasis was also detected at pathological exam. She received chemotherapy postoperatively and remains alive without evidence of disease. The recurrence of cervical cancer is traditionally regarded as an issue concerning the cervix, the parametria, or the lymph nodes. When the uterus is preserved we must also consider the possibility of a recurrence involving the corpus. With wider acceptance of limited therapeutic approaches we must be prepared for the detection of previously unknown patterns of recurrence and the follow-up modalities must be consequently adapted.

[Nephrogenic adenoma of the bladder. Morphological and immunophenotypic study with particular attention to differential diagnosis]. / Adenoma nefrogenico della vescica. Studio morfologico ed immunofenotipico con particolare attenzione alla diagnostica differenziale.

BACKGROUND: Nephrogenic Adenoma (NA) is a rare lesion of the urinary tract, considered a metaplastic response to chronic inflammation, trauma or immunosuppression. METHODS AND RESULTS: We report two cases of NA arising in the urinary bladder of patients with previous history of recurrent urinary tract infections due to neuropsychiatric disease. Pathological examination of the lesions, resected by transurethral (TUR) management, revealed a papillary proliferation of tubules and cysts lined by cuboidal to low-columnar cells without atypia. Immunohistochemistry showed positivity for Cam 5.2, CK7 and EMA. MIB 1 count demonstrated a positivity in 12/200 cells in case 1 and < 2/200 in case 2. No expression of nuclear p53 was evident. CONCLUSION: NA is a benign unusual neoplasm which might be misdiagnosed as clear cell adenocarcinoma of the bladder or prostatic adenocarcinoma. Its recognition is important because it is a benign lesion cured by a conservative resection and no additional therapy is generally required.

Gastrointestinal autonomic nerve tumor (plexosarcoma): report of a case with fine needle aspiration biopsy and histologic, immunocytochemical and ultrastructural study.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) encompass a large group of mesenchymal neoplasms that display common cytologic spindle-shaped morphology on light microscopy. Immunocytochemical and ultrastructural studies can demonstrate several patterns of differentiation. CASE: A 70-year-old male presented with two intraabdominal small bowel masses. The cytopathologic features of a fine needle aspiration biopsy (FNAB) included plump spindle cells in densely populated aggregates or in a fasciculated pattern, without significant pleomorphism. An epithelioid component in a lobular arrangement with abundant, eosinophilic cytoplasm was also noted. The nuclei were vesicular, with a very evident, eosinophilic nucleolus and finely distributed chromatin. Groups of loosely cohesive cells with slender, dendritic-like cytoplasm were evident. Immunocytochemical study of the embedded, fine needle aspirated fragments of the neoplasm demonstrated immunoreactivity for vimentin and neuron-specific enolase. Cytokeratin immunoreactivity or muscular, vascular, neuroendocrine or nerve sheath differentiation failed to be demonstrated. The cytologic and immunocytochemical findings correlated well with the histologic features of the neoplasm. The morphologic diagnosis was confirmed by ultrastructural study. CONCLUSION: FNAB and immunocytochemistry can be valuable in making the correct diagnosis between gastrointestinal stromal tumors.

Sporadic fundic gland polyps: an immunohistochemical study of their antigenic profile.

Fundic Gland Polyps (FGPs) are small sessile (2-5 mm), usually multiple polyps arising in the gastric, acid-secreting mucosa of disputed histogenesis. They have been described in a sporadic form, prevalently in middle aged females, or associated with familial adenomatosis coli-Gardner's syndrome. We performed an immunohistochemical study on 24 sporadic FGPs, using monoclonal antibodies (MAbs) against differentiation markers, class II MHC antigens (HLA-DR), oncofetal and proliferation antigens, aimed to characterize the antigenic profile of the polyps. A preliminary cytogenetic study on five polyps was also done, using an in situ culture method after collagenase treatment. Cytokeratins 8-18 (CAM 5.2 MAb) and 20 (IT-Ks 20.8 MAb), Epithelial Membrane Antigen (EMA) and Chromogranin A were normally expressed by FGPs. FGPs did not express HLA II DR. FGPs did not react with an anti-CEA MAb (F6), but they were frequently positive (22/24, 91.6%) with B72.3 MAb (reacting with the cancer-associated mucin epitope sialyl-Tn). The PC10 MAb (against PCNA or cyclin) showed enhanced expression in the deep glandular-cystic compartment of FGPs; the PCNA index of FGPs was significantly higher than in normal fundic mucosa. The cytogenetic study on the 5 cases analysed, revealed a normal karyotype. We have demonstrated that FGPs express in the paranuclear zone the sialyl-Tn epitope, a side-chain sugar normally masqued in adult gastric mucins, thus revealing an alteration in mucin synthesis; FGPs' higher proliferation index as compared with normal fundic mucosa supports the hypothesis of their hyperproliferative nature.

Ganglioglioma: a clinical and pathological study of 12 cases.

We report the clinico-pathological and immunohistochemical findings of 12 cases of gangliogloma that were diagnosed at Legnano Civil Hospital over a period of 10 years. The patients' age at presentation ranged from 2-69 years with a mean duration of symptoms equal to 52 months. Seizures were the most common presenting symptoms. These tumors, mainly located in the temporal lobe (5/10), displayed in 10 cases a low density appearance at CT scan. Histologically the tumors were composed of neoplastic ganglion cells mixed together with a glial component. All but one of the tumors were surgically treated: complete removal was accomplished in 8 cases and incomplete in 3 cases; 1 case was an incidental autopsy finding. Radiotherapy was administered in the incompletely removed cases. The mean follow-up period was 40.8 months, with 3 patients deceased. Our findings support the notion that ganglioglioma is a slow-growing relatively benign tumor of young adults, ubiquitous in the central nervous system with a non-specific CT scan appearance and varied histological morphology, in which immunochemical stains will confirm the diagnosis and could provide a prognostic marker.

Sarcomatoid carcinoma of the colon. Report of the second case with immunohistochemical study.

Sarcomatoid Carcinomas are rare tumors composed of mixed malignant epithelial and mesenchymal cells. Only one case is reported in the colon, up to date. We describe the second case in an 86-year-old woman. The tumor, replacing the intestinal wall, consisted of carcinomatous and sarcomatous areas. The former was composed of differentiated superficial adenocarcinoma and of infiltrating epithelioid undifferentiated solid portion. The latter was mostly composed of undifferentiated spindle cells with focal chondrosarcomatous and pleomorphic anaplastic areas. A strong Cytocheratin (CK) and Epithelial Membrane Antigen (EMA) immunoreactivity (IR) with focal CA 125 positivity was detected in differentiated adenocarcinomatous areas. Solid carcinoma-like areas coexpressed CK and Vimentin (VIM). The sarcomatous spindle-cell component of the tumor was largely VIM positive, with focal CK IR. Both polyclonal and monoclonal antibodies for Carcino-Embryonic Antigen (CEA) did not display any reaction.

Atrio-ventricular nodal tumor associated with polyendocrine anomalies.

We report the clinical and autopsy findings of a young female suffering of complete heart block since the age of 11 and who suddenly died at the age of 32 because of a polycystic atrio-ventricular node tumor. In association with this tumor, we observed a hyperplasia of the islets of Langherans, a true thymic hyperplasia, bilateral multicystic ovaries, adrenal tissue heterotopia and clear cell adenomatosis in the right kidney. We suggest that the polycystic atrio-ventricular node tumor may be part of a complex syndrome with endocrine disorders and heterotopias.

Placental teratoma with three-germ layer differentiation.

A rare case of placental teratoma is described. Major features were the presentation as a pedunculated mass from the fetal surface of the placenta, the mixture of different tissues derived from all three germ layers (skin with dermal appendages, ganglion-like cells, and nervous structures, gut structures, osteocartilagineous and smooth and striated muscle), and the absence of segmental organization.

Tripartite differentiation (squamous, glandular, and melanocytic) of a primary cutaneous neuroendocrine carcinoma. An immunocytochemical and ultrastructural study.

We report a case of primary cutaneous neuroendocrine carcinoma (PCNEC) with squamous, glandular, and melanocytic differentiation and associated Bowen disease. The paranuclear globular positivity of low-molecular-weight cytokeratins agrees with the ultrastructural observations of paranuclear fibrous bodies in the small neuroendocrine cells, while the diffuse cytoplasmic positivity corresponds to the sparse intermediate filaments in large cells with squamous differentiation. "Transitional forms" are characterized by both diffuse and globular cytoplasmic positivity for cytokeratins and by the ultrastructural evidence of neuroendocrine and squamous features. Therefore the ultrastructural demonstration of intracytoplasmic tonofibrils and tonofilaments, intercellular glandular lumina, lined by well-formed microvilli, and immature premelanosomes in the neurosecretory cells supports the proposed tripartite differentiation of neuroendocrine cells of this case of PCNEC.

A case of malignant phyllodes tumor with muscular and fatty differentiations.

A 50-year-old female underwent surgical removal of a mammary phyllodes tumor, whose peculiar histologic feature was the coexistence of areas of liposarcoma and leiomyosarcoma. The morphologic differential diagnosis is briefly discussed.

[Glial heterotopy of the nose ("nasal glioma"). Description of a case]. / Eterotopia gliale del naso ("glioma nasale"). Descrizione di un caso.

A six months female infant was admitted in our hospital for congenital dysmorphism of face: a subcutaneous nodule in left nose region was present. An x-ray study showed relevant scoliosis of the nasal septum. On surgery a white firm nodule was incompletely excised; a post-operatory CT-scan excluded any communication of neoplasia with brain. No bone lacunae were seen. Clinically there was neither rhinorrhea nor meningitis. The baby was discharged on 7th day. Grossly the mass presented white surface, firm consistency with small hemorrhages on cut surface. Microscopically the nodule, encircled by a fibrous pseudo-capsule, was mostly composed of gemistocytic astrocytes, occasionally binucleated, interspersed within fibrillary neuroglial tissue. Strands of fibrous tissue, in continuity with the pseudo-capsule, separated the glial tissue. No neuronal cells were seen. Necrosis, mitotic figures and vascular proliferations were absent. GFAP immunohistochemical stain confirmed the glial nature of the cells. Our diagnosis was one of "heterotopic glial tissue of nose" (nasal glioma). The absence of connection between the nodule and endocranial contents (CSF-filled spaces, leptomeningeal or dural tissue), excluded the diagnosis of encephalocele. In our case, the tissue was only of embryonic neuroectodermal derivation: on this basis the diagnosis of teratoma, which is classically composed of two or three embryonic layers could be excluded. The pathogenesis of nasal glioma is briefly discussed by authors.