Adenomatous Differentiation Research Articles

Clinicopathological characteristics of SMARCB1(INI1)-deficient sinonasal carcinoma

Objective: To investigate the clinicopathological characteristics, diagnosis, differential diagnosis and prognostic factors of SMARCB1 (INI1)-deficient sinonasal carcinoma (SDSC). Methods: Sixteen cases of SDSC diagnosed in the Department of Pathology, Beijing Tongren Hospital from January 2016 to September 2020 were enrolled. Ninety-nine cases of small round cell malignant tumors of the head and neck were selected as the control, including poorly-differentiated squamous cell carcinoma (n=10), poorly-differentiated adenocarcinoma (n=5), undifferentiated carcinoma (SNUC, n=4), NUT carcinoma (n=5), neuroendocrine carcinoma (n=10), and other non-epithelial tumors [olfactory neuroblastoma (n=10), rhabdomyosarcoma (n=10), NK/T-cell lymphoma (n=10), malignant melanoma (n=10), Ewing's sarcoma/primitive neuroectodermal tumor (EWS/PNET, n=5)] and non-keratinizing undifferentiated nasopharyngeal carcinoma (n=20). The clinical and pathologic characteristics of SDSC, and immunohistochemical (IHC) expression of broad-spectrum CKpan, CK7, CK8/18, CK5/6, p63, p40, p16, INI1, NUT and neuroendocrine markers (Syn, CgA, CD56) were evaluated. In situ hybridization (ISH) was used to detect EBER and fluorescence in situ hybridization (FISH) to detect INI1 gene deletion. Results: The 16 cases of SDSC accounted for 1.3% (16/1 218) of all malignant sinonasal tumors in the author's unit during this time period, and 2.4% (16/657) of all malignant epithelial tumors. Microscopically, there was no clear squamous and adenomatous differentiation, but "rhabdoid-like" cells, are often seen. All SDSC cases were positive for CKpan and CK8/18, negative for INI1; Epstein-Barr virus was not detected by ISH; and INI1 gene deletion was observed in all 11 SDSC patients with FISH. Twelve cases were followed up for 3-47 months. One died of tumor-related diseases half a year after diagnosis, and the remaining patients were alive with tumor, the longest survival time was 47 months. Conclusion: SDSC should be differentiated from a variety of poorly-differentiated tumors in the sinonasal area. Histologically, SDSC has no clear differentiation, but the tumor cells are characteristically basal-like or rhabdoid-like, with non-specific vacuoles, translucent or vacuolar nuclei, prominent nucleoli and necrotic foci. They are negative for INI1 IHC staining, and FISH demonstrates INI1 gene deletion. The clinical prognosis is still unclear, further studies on its biologic behavior and treatment methods are warranted.

Differences in the ARID-1 alpha expressions in squamous and adenosquamous carcinomas of uterine cervix.

AT-rich interactive domain 1A (ARID1A) is a tumor suppressor gene involved in chromatin remodeling which encodes ARID1A (BAF250a) protein. Recent studies have shown the loss of ARID1A expression in several types of tumors. This retrospective study was designed to evaluate the differences in tissue expressions of ARID1A in a spectrum of cervical neoplasms. Cervical intraepithelial neoplasms, invasive squamous or adenosquamous carcinomas were identified in 100 patients recently diagnosed as cervical neoplasms based on pathology databases. In this series, there were 29 low- and 29 high-grade cervical intraepithelial neoplasms, 27 squamous cell carcinomas, and 15 adenosquamous carcinomas. Mean age of the patients was 47.8±13years (20-80years). It was determined that the expression of ARID1A was statistically significantly down-regulated in adenosquamous carcinomas when compared with non-invasive or invasive squamous cell carcinomas (p=0.015). Lower levels of the ARID1A expression were detected in cases with adenosquamous carcinomas (60%), low- or high-grade squamous intraepithelial lesion (SIL) (31%), and squamous cell carcinomas (18.5%). Our findings have demonstrated the presence of a correlation between ARID1A expression and adenomatous differentiation of uterine squamous cell carcinomas. Therefore, ARID1A gene may suggestively have a role in the pathogenesis of cervical adenosquamous carcinomas.

Rhabdoid Large Cell Carcinoma of Lung, With Illustrative Immunohistochemical and Molecular Findings

Large cell carcinomas with rhabdoid phenotype (LCC-RP) account for <1% of pulmonary large cell carcinomas and are associated with extremely poor prognosis. We report a case of a 64-year-old male patient who presented at an advanced stage with a LCC-RP, arising from a poorly differentiated adenocarcinoma of the lung. Ninety percent of the tumor consisted of large pleomorphic rhabdoid tumor cells that showed eosinophilic cytoplasmic inclusions and the remaining 10% showed evidence of adenomatous differentiation. Rhabdoid areas were immunohistochemically positive for pan-cytokeratin AE1/3, epithelial membrane antigen, vimentin, thyroid transcription factor-1, integrase interactor-1, and negative for desmin. Nuclear positivity was absent for Myo-D1. The parent adenocarcinoma was positive for thyroid transcription factor-1 and cytokeratins 7. Epidermal growth factor receptor mutation analysis revealed the same mutation (p.delL747-T751) in both areas, suggesting that the malignant rhabdoid phenotype represents a dedifferentiation phenomenon of the adenocarcinoma. This is the first reported case of an Exon 19 deletion in epidermal growth factor receptor of the activating type detected in a LCC-RP associated with a poorly differentiated pulmonary adenocarcinoma.

Expression of carbonic anhydrase IX in genitourinary and adrenal tumours

High expression of carbonic anhydrase IX (CAIX) is reported for clear cell renal cell carcinoma (RCC), with a paucity of data for non-renal genitourinary or adrenal tumours. This study investigated the immunohistochemical expression of CAIX throughout the genitourinary tract and adrenal gland. High expression in the renal cortex was restricted to clear cell, papillary and clear cell papillary RCC and carcinoid. Core biopsies of clear cell RCC were consistently positive. Positivity within the urothelial tract was seen in urothelial carcinoma including squamous, small-cell, sarcomatoid and adenomatous differentiation and clear cell adenocarcinoma. Signet ring and plasmacytoid variants of urothelial carcinoma were negative. Phaeochromocytoma, adrenal cortical adenoma, seminoma, yolk sac tumour, choriocarcinoma, Leydig cell tumour and prostatic adenocarcinoma were predominately negative, with variable reactivity in adrenal cortical carcinoma, embryonal carcinoma, teratoma and Sertoli cell tumour. Carbonic anhydrase IX is a sensitive marker for clear cell RCC in core biopsies. However, other genitourinary or adrenal tumours that can have a clear cell appearance including urothelial, squamous cell, clear cell adeno and adrenal cortical carcinoma and Sertoli cell tumour express CAIX. Knowledge of expression overlap between these entities may prevent incorrect interpretation of immunohistochemical results, particularly if limited tissue is available.

Adenoendocrine carcinoma of the accessory papilla of the duodenum: Report of a case

This report describes a very rare case of an adenoendocrine carcinoma of the accessory papilla of the duodenum. A 70-year-old woman was admitted to the hospital complaining of epigastralgia. Gastrointestinal endoscopy showed a protruding tumor with ulceration at the accessory papilla of the duodenum. A biopsy revealed a small-cell carcinoma. Computed tomography showed a highly enhanced tumor in the early phase. No metastatic lesions were shown. Magnetic resonance cholangiopancreatography showed dilatation of the pancreatic duct, but a normal common bile duct. A pyloruspreserving pancreaticoduodenectomy was performed with lymph node dissection. Microscopically, the tumor was a small-cell neuroendocrine carcinoma with adenomatous differentiation. An immunohistochemical analysis showed positive staining for synaptophysin, chromogranin A, CD56, and carbohydrate antigen 19-9. The final diagnosis was an adenoendocrine carcinoma with lymph node metastasis. The postoperative course was uneventful and the patient is now doing well as an outpatient after 14 months of follow-up.

Successful enucleation of a giant cardiac hemangioendothelioma showing an unusual proliferation pattern

As a pathologic entity this particular subtype may not constitute a distinct tumor from the other types of clear cell tumors, as suggested in the early 1980s. However, further clinicopathologic, immunohistochemical, and ultrastructural studies of subsequent case reports support CCC as a distinct subtype of large cell carcinoma with purely clear cell features or classified into squamous or adenomatous variants, depending on the type of cellular differentiation. In our case, no squamous or adenomatous differentiation was seen, and the tumor grew into and completely occluded the right main bronchus. This biologic behavior appears to be more benign than that seen in other types of non–small cell lung cancer.

Mucoepidermoid carcinoma arising within nevus sebaceus of Jadassohn.

Nevus sebaceus (NS) of Jadassohn is a common congenital lesion associated with numerous benign and malignant tumors. However, mucoepidermoid carcinoma (MEC) has not been described in association with NS. We describe an unusual case of MEC arising within NS. A 72-year-old man presented with an enlarging plaque on his forehead, along the hairline. Physical examination revealed a mounded, erythematous lesion that was completely excised. Histological evaluation revealed a typical MEC with areas of squamous and adenomatous differentiation with foci of typical intermediate cells. The diagnosis of MEC is an important one, because it portends a poor prognosis, requiring long follow-up. This is, to our knowledge, the first report of MEC arising within NS.

Tubular differentiated stomach carcinoma of the (Ming) infiltrating type

Gastric carcinoma of the infiltrative type (according to Ming) occasionally shows adenomatous differentiation only. Over the past 18 years, we have observed 23 cases of this tumour type, accounting for 3.6% of all surgically treated gastric carcinomas. Macroscopically they were classified as Borrmann IV or III, while histologically most of them were well differentiated. Histologically, these tumours retained the pre-existing structures of the stomach, most readily observable at the tunica muscularis propria; a pronounced desmoplasia was also characteristic, particularly in the submucosal and subserosal layers. In all cases the tumour tissue spread inside lymphatic vessels. All but 2 cases with metastatically involved lymph nodes, often small, showed infiltration of the lymph node sinus; in three quarters of cases the serosa was infiltrated by the tumour. Significant findings among the patients under observation for extended periods included bilateral ovarian metastases in 4 of 5 women examined and tumour recurrence at the anastomosis in 6 of 9 patients in whom Billroth II operation had been performed. The mean survival time of 16 patients was 14.9 months. Owing to the diffuse type of tumour growth, extensive surgery is recommended as in cases of signet ring cell cancer. The high incidence of small lymph node metastases from this type of tumour should also be taken in account preoperative staging. Preoperative diagnosis of this tumour subtype is difficult, because histological criteria alone do not allow clear identification. Close cooperation with clinical investigators is necessary, and intraoperative assessment of the tumour--including frozen section of necessary--in particular is of the utmost importance.

Alpha-amylase in resectable lung cancer: Lenler-Petersen P, Grove A, Brock A, Jelnes R. Topasdalen 8, DK-8900 Randers. Eur Respir J 1994;7:941–945

Biochemical analysis and immunohistochemical techniques support the theory that hyperamylasaemia in lung cancer is due to amylase production in carcinoma cells. The vast majority of amylase-producing carcinomas are adenocarcinomas with amylase isoenzyme similar to the salivary type. This prospective study assesses alpha-amylase expression in resectable lung cancer. Seventy four patients with resectable lung cancer were studied. Amylase activity in tumour tissue was analysed and isoamylase identification performed. Immunohistochemical analysis was performed using a polyclonal rabbit antibody against human salivary amylase. Hyperamylasaemia occurred in 13 out of 70 patients. Increased amylase activity in tumour tissue was found in 10 out of 52 cases, of which only two were associated with hyperamylasaemia. With the exception of one large cell carcinoma and one squamous cell carcinoma, the tumours were adenocarcinomas. Immunohistochemical analysis revealed amylase expression in seven adenocarcinomas and two adenosquamous carcinomas. In conclusion, immunohistochemical amylase expression was restricted to carcinomas with adenomatous differentiation. Biochemical analysis confirmed amylase production in 5 of 7 cases examined, the tissue amylase isoenzymes being of salivary type. However, hyperamylasaemia and a slightly increased amylase activity in tumour tissue may be caused by factors other than amylase-producing carcinoma cells.

The Value of Immunohistochemistry of Pleural Biopsy Specimens in the Differential Diagnosis between Malignant Mesothelioma and Metastatic Carcinoma

The aim of the present study was to evaluate the aid of immunohistochemistry in the differential diagnosis between pleural malignant mesothelioma (MM) and secondary pleural carcinoma in pleural biopsy specimens. A series of MM (epithelial or biphasic type) (n = 39), and a series of secondary pleural carcinomas (n = 25) were studied with a panel of monoclonal antibodies against Ber-EP4, CEA, and Leu-MI (CD-15). Considering the markers one, two or three at a time, computer analysis was conducted to identify the immunophenotype with the highest sensitivity and specificity for both MM (n = 39) and adenocarcinoma (n = 19). The CEA/CD-15 marker combination had the highest specificity (MM = 100%; adenocarcinoma = 82.1%), and sensitivity (MM = 82.1%; adenocarcinoma = 100%) considering both categories of tumours. Positive reaction for CEA and/or CD-15 was the best indicator of metastatic adenocarcinoma. Negative reaction for CEA/CD-15 and Ber-EP4/CD-15 showed up to be 100% specific for MM. Positive reaction for one, two or even all these antigens, however, occurred in nine tumours predetermined as MM according to their gross appearance, and absence of other primary malignancies at autopsy. Ultrastructural examination (n = 7) of these tumours strongly supported the diagnosis in one case, and did by no means exclude the diagnosis MM in the other six cases. Neither did any of the tumours reveal ultrastructural signs of adenomatous differentiation, and they did not express PAS/diastase resistant globules, amylase or surfactant. Anti -Ber-EP4 was the antibody most frequently expressed in MM (n = 8). Until antibodies specific for MM are available, the limitation of immunohistochemistry to solve the diagnosis in all cases of pleural malignant tumours has to be considered.

Alpha-Amylase in resectable lung cancer

Biochemical analysis and immunohistochemical techniques support the theory that hyperamylasaemia in lung cancer is due to amylase production in carcinoma cells. The vast majority of amylase-producing carcinomas are adenocarcinomas with amylase isoenzyme similar to the salivary type. This prospective study assesses alpha-amylase expression in resectable lung cancer. Seventy four patients with resectable lung cancer were studied. Amylase activity in tumour tissue was analysed and isoamylase identification performed. Immunohistochemical analysis was performed using a polyclonal rabbit antibody against human salivary amylase. Hyperamylasaemia occurred in 13 out of 70 patients. Increased amylase activity in tumour tissue was found in 10 out of 52 cases, of which only two were associated with hyperamylasaemia. With the exception of one large cell carcinoma and one squamous cell carcinoma, the tumours were adenocarcinomas. Immunohistochemical analysis revealed amylase expression in seven adenocarcinomas and two adenosquamous carcinomas. In conclusion, immunohistochemical amylase expression was restricted to carcinomas with adenomatous differentiation. Biochemical analysis confirmed amylase production in 5 of 7 cases examined, the tissue amylase isoenzymes being of salivary type. However, hyperamylasaemia and a slightly increased amylase activity in tumour tissue may be caused by factors other than amylase-producing carcinoma cells.

Histochemical and ultrastructural analyses of glandular differentiation in typical carcinoid tumor of the hindgut.

Adenomatous differentiation of typical carcinoid tumors was examined by histochemical and ultrastructural studies on 33 cases of typical carcinoids of the hindgut. Of these 33 carcinoids, 12 (36%) showed a tubular and/or acinar pattern with production of mucus as a minor component. A few tumor cells with mucous globules were scattered among tubules in these carcinoids. Ultrastructurally, microvilli were seen along the luminal surface of tubules, with both numerous mucous globules in the supranuclear area and endocrine granules in basal sites of the same cells. These results indicate that even in typical carcinoid tumors, certain tumor cells have the features of goblet cells or the open type of endocrine cells. The findings of both mucous globules and endocrine granules in the same single cells indicate a close relationship between endocrine cells and mucus-producing and/or tubule-forming cells. It is concluded that pluripotential cells producing carcinoid tumors might be able to differentiate into three types of tumor cells: (i) endocrine cells without microvilli or mucus production; (ii) cells with microvilli and no mucus product; and (iii) mucus-containing cells with microvilli.

Serological screening for a mucine-like carcinoma-associated antigen (MCA) in patients with gastrointestinal tract malignancies.

Mouse monoclonal antibody b-12 identifies a high-molecular-mass glycoprotein antigen strongly expressed by breast carcinoma cells. Since immunohistochemical studies have also demonstrated some reactivity with other epithelial neoplasms, and since "mucine-like carcinoma-associated antigen" (MCA) has gained considerable interest as a tumor marker in breast cancer, we have investigated 34 patients with histologically proven advanced gastrointestinal malignancies for the presence of elevated MCA serum levels. Our data suggest that screening for and/or monitoring of MCA in these tumors is unlikely to have any practical clinical relevance. The possible role of MCA as a marker in tissue specimens for abortive adenomatous differentiation in gastrointestinal (and other) neoplasms, however, remains to be determined.

The immunohistochemical reactivity of a new anti-epithelial monoclonal antibody (MAb b-12) against breast carcinoma and other normal and neoplastic human tissues

A mouse monoclonal antibody, MAb b-12, has been described previously (Stähli et al. 1985) which reacts with a Mr 350 kD glycoprotein with mucin-like characteristics (Stähli et al. 1987) expressed in cytoplasm and on the surface of human breast carcinoma cell lines (MCF-7 and ZR-75-1). In the present report the immunohistochemical reactivity of this MAb with normal and malignant human tissues is analyzed. Pre-experiments showed that the epitope b-12 is resistant to formalin treatment allowing the use of tissue processed by standard paraffin embedding methods. 167 normal and 408 neoplastic tissues were tested by indirect immunofluorescence or the avidin-biotin complex method. MAb b-12 stained the apical cytoplasm of secretory epithelia and their secretions including the acinar and ductular epithelia of the breast. It reacted with all breast carcinomas independent of their histological type or stage, frequently with all but in some cases with a fraction of the tumour cells. Some other carcinomas, primarily those of adenomatous differentiation, were also reactive. In these, however, the fraction of positive tumour cells was usually lower. The b-12 epitope is thus a marker for normal and neoplastic epithelia with secretory functions, particularly for breast carcinomas of all histological types and stages, and perhaps a differentiation marker for abortive adenomatous differentiation in solid carcinomas of the gastro-intestinal, uro-genital or respiratory tract.

Transformation of a rat liver cell line: Neoplastic phenotype and regulation of gamma glutamyl transpeptidase in tumour tissue

A continuously dividing but non-transformed rat cell line was transformed by ras oncogenes and by aflatoxin. Transformed lines grew as solid tumours in nude mice with a short latency period. Different phenotypes were obtained from the transformed clones, and covered a wide spectrum of tumour types. While the commonest tumour type obtained was undifferentiated with unorganised spindle shaped and rounded cells, tumours with well formed trabeculae and adenomatous differentiation were also obtained. Gamma glutamyl transpeptidase (GGT), which showed an increase in transformed cells in tissue culture showed a variable expression in nude mouse tumours. While GGT positive cells were seen in all types of tumours they followed no consistent pattern and GGT negative areas were seen with a high frequency. However, in tumours showing adenomatous differentiation it was confined to the membrane on the luminal surface of the glandular structures. The different types of tumours resulting from the transformation of a single cell line provide a model of in vivo tumour development, supporting the possibility of a single stem cell origin of different types of liver neoplasms. This system also demonstrates the complexity of the regulation of GGT in tumour tissue. The influence of GGT on tumorigenesis has also been studied.

Adenosquamous Carcinoma of the Skin

Two cases of an aggressive cutaneous carcinoma showed both squamous and adenomatous differentiation. These neoplasms invaded subcutaneous structures with a sclerosing pattern, making surgical resection difficult. Unlike the usual squamous carcinoma, glands and epithelial mucin (sialomucin) were produced. This mucin stained with mucicarmine and was sensitive to sialidase and resistant to hyaluronidase digestion. No mucin with similar histochemical properties was found in a study of 50 consecutive cutaneous squamous carcinomas and 50 consecutive basal cell epitheliomas from our files. Literature reports of histologically similar cutaneous carcinomas together with our experience with these two cases suggest aggressive behavior for this category of neoplasm.

Ultrastructural investigation of anaplastic salivary gland carcinomas in Eskimos.

Ultrastructural investigation of 19 malignant lymphoepithelial salivary gland tumors in Greenland Eskimos disclosed evidence of epithelial origin of the tumor cells in 18 cases. Furthermore, tumor cells exhibited markers of squamous cell differentiation in 16 cases. Signs of adenomatous differentiation were never encountered. Thus, the malignant lymphoepithelial tumor of salivary glands is the ultrastructural counterpart to the nasopharyngeal anaplastic carcinoma (malignant lymphoepithelioma), both being high-grade squamous cell carcinomas.

Mucoepidermoid carcinoma of the breast: high grade variant

The mucoepidermoid carcinoma is a very rare neoplasm of the breast which histologically resembles mucoepidermoid carcinoma in the salivary glands. It is characterized by sheets of epidermoid cells with area of definite squamous differentiation as well as glandular and cystic spaces lined by atypical mucin-secreting columnar cells. The ultrastructural findings reflect the squamous and adenomatous differentiation seen on light microscopy. The degree of histological differentiation and the infrequency of nodal metastasis suggest an indolent behaviour. This is supported by the absence of recurrence or death due to the disease in 7 of the 8 cases reported to date. Only 1 patient has had extensive axillary nodal metastasis from a mucoepidermoid carcinoma which showed large areas of poorly differentiated cells. The present case is another example of such a high grade variant in which death occurred from pulmonary and vertebral metastases within 6 mth of mastectomy. An aggressive behaviour should be predicted by the presence of a large undifferentiated component in the tumour, necrosis and prominence of mitoses.

Ultrastructure of the Lewis lung carcinoma

Electron microscopic observations were made on the Lewis lung carcinoma, which has frequently been used in various experiments. Although the tumor cells had desmosomes, interdigitations, microvilli and basement membranes which were of epithelial nature, they did not show either squamous or adenomatous differentiation. On the basis of microscopic and ultrastructural findings, this tumor falls into the category of large cell carcinomas. At the periphery of the tumor, sinusoidal clefts between the strands of tumor cells contained many red blood cells without fibrin. While perfect blood vessels were observed towards the center of the tumor, large necrotic areas were observed. Dilated large vessels possessed some endothelial fenestrations. Light endothelial cells were also observed, which were penetrated by red blood cells. Interstitial components were very scant and collagen fibres were frequently observed to be dissolved.