Composite enteric-type adenocarcinoma-carcinoid of the nasal mucosa

Case Report

Composite Enteric-type Adenocarcinoma-Carcinoid of the Nasal Mucosa Marzia Bonato, M.D., Bruno Frigerio, M.D., Carlo Capella, Ph.D., Anna Maria Chiaravalli, B.D., and Michele Cerati, M.D.

Abstract The authors describe a patient whose nasal neoplasm demonstrated histological characteristics of both a moderately differentiated intestinal-type adenocarcinoma and an atypical carcinoid (well-differentiated neuroendocrine carcinoma). The adenocarcinoma displayed a predominantly papillary architecture, immunohistochemicatly positive staining for intestinal markers, and ultrastructural features {microvilli with tong roots) characteristic of intestinal differentiation. The carcinoid component was argyrophilic, was immunoreactive with chromogranin, gastrin, and serotonin, and displayed ultrastructurally characteristic G and EC cells. The neoplasm recurred twice, and the tumor tissue from the second recurrence was composed only of neuroendocrine cells, indicating that this component was more resistant to the therapy {surgery and radiotherapy) employed. The patient died from an intracranial recurrence 5 months after the last combined surgical and radiotherapic treatment. Because of its unfavorable prognosis, a neuroendocrine-exocrine tumor should not be grouped with typical carcinoids or with well-differentiated papillary sinonasal adenocarcinomas, which seem to be less aggressive. Endocr Pathoi 4:40-47, 1993,

Department of Human Pathology, lI Medical Faculty, University of Pavia at Varese, and Multizonal Hospital, Varese, ltaly (MB, CC, AMC, MC); and General Hospital of Saronno, Saronno. Italy

(B~3. Address correspondence to Profi C. Capella, Servizio di Anatomia e lstologia Patotogica, Ospedale Mulrizonale, Viale Borri 57, 21100, Varese, italy. 9 1993 Blackwell Scientific Publications, Inc.

Forty-seven years have passed since Jarvi [16] described the first case of primary enteric-type adenocarcinoma of the sinonasal cavities in 1945 and stressed the occurrence of argentaffin cells in addition to columnar, goblet, and Paneth's cells within these tumors. Since that time the pathology of enteric-type sinonasal adenocarcinomas including their neuroendocrine (NE) component has been more clearly delineated at both the light and electronmicroscopic level [2, 2t, 25-27]. Similarly much information has been gathered about tumors of the diffuse NE system (carcinoids) [13, t9, 28] and the so-called composite carcinoma-carcinoid tumors exhibiting both adenocarcinomatous and carcinoid differentiation [3, 32]. Composite neuroendocrine-~exocrine tu-

mors have been reported in various sites including the esophagus [7], stomach 161, gall bladder [321, colon [201, pancreas [8], appendix [15], and prostate [51 . In the nasal cavity only one case o f endocrine-amphicrine enteric-type carcinoma has been reported so far [26]. In this report we describe a unique case of a patient with a composite atypical carcinoid-enteric-type adenocarcinoma of the nasal cavity. This investigation includes light and electron microscopy as well as immunohistochemical detection of several neuroendocrine and exocrine tmnor markers. The relationship between enterictype adenocarcinomatous and carcinoid components, the possible origin of the tumor, and criteria for diagnosis of nasal neuroendocrine-exocrine tumors are briefly discussed.

Nasal Adenocarcinoma-Carcinoid

Case Report A 52-year-old male printer with a short history of headache underwent a computed tomography (CT) scan in June 1984. A mass originating from the ethmoidal lamina cribrosa and budding into the anterior cranial fossa with compression of the dura was disclosed. In July 1984 a right frontal craniotomy was performed with removal of a mucoid, translucent, well-circumscribed extradural mass. After this operation a residual neoplastic mass was detected in the right upper nasal cavity and in the frontal and sphenoidal sinuses. A radical operation of the tumor was then performed and was followed by radiotherapy. In January 1986 the patient complained of diplopia due to a right exophthalmos, A CT scan revealed a mass involving both the right ethmoidal and frontal sinuses and invading the medial side of the right orbit. The patient was treated again with surgery combined with postsurgical radiotherapy. Six months later the patient died from intracranial tumor recurrence. Permission for autopsy was refused.

Material and Methods For light microscopy the tissue samplcs obtained from the first and third operations were fixed in 10% buffered formalin and embedded in paraffin. Sections 5/~m thick were stained with hematoxylin and eosin (H&E), Alcian blue (AB)pH 2,S-periodic acid-Schiff (PAS), high iron diamine (HID)-AB, Grimelius' silver stain, and diazonium test for cells storing 5-hydroxytryptamine (5-HT). Amphicrine cells were identified by combining Grimelius' silver impregnation with AB. For immunohistochemistry the antibodies employed with their respective dilutions are listed in Table 1. Immune reactions were revealed by the avidin-biotinperoxidase complex (ABC) technique according to Hsu et al. [14] and developed with diaminobenzidine. The antisera employed were applied for 16-48 hours at 4~ Controls for the specificity ofimmuno-

4|

staining were performed by using rabbit, goat, or mouse nonimmune serum as first layer; by incubating adjacent sections with diluted antiserum preadsorbed with 1-50 b~g/ml of the respective antigen; and by omitting the first layer. Specimens for electron microscopy were obtained from paraffin blocks of tumor tissue taken at the first operation, refixed in phosphate-buffered paraformaldehyde-glutaraldehyde mixture, postfixed in 1% OsO4, dehydrated in graded ethanols, and embedded in Epon. For orientation sections 1 /.tm thick were stained with toluidine blue. The thin sections were stained with uranyl acetate and lead citrate and studied on a Zeiss EM 10 electron microscope at 60 kW.

Results Histology and Histochemistry

The tumor tissuc from the first operation and that from the third operation had different histological and histochemical features. In the first, the tumor showed a pattern typical of papillary-tubular cylinder cell adenocarcinoma (Fig. 1), which was combined with orderly solid nests and microacini characteristic of carcinoid tumor. The papillae and tubules were lined by moderately differentiated columnar cells with their vesicular nuclei located in a predominantly basal position and an apical brush border similar to that of intestinal absorptive cells. In some areas with adenocarcinomatous features some goblet cells, columnar cells with few mucus droplets in the apical cytoplasm, and numerous neuroendocrine (NE) cells dispersed as scattered elements or forming linear chains or micronodules were also seen. The latter seemed to merge gradually with the carcinoid component. The NE cells were rounded, triangular, and apposed to the basement membrane, with pink granules (in H&E preparations) which were copious and usually situated in the basal cytoplasm. The carcinoid component was represented by sheets, nests, and acini o f polygohal cells with fine granular eosinophilic cytoplasms and rather large hyperchro-

42

Endocrine Pathology

Volume 4 Number 1 March 1993

I Table I.

Details of the polyctonal (PC) and monoclonat (MC) antibodies used

Antibodies Against

Ref. No.

CAR-5 human sulfated colorectal glycoprotein [9, 24] (MC) Human foveolar gastric fucomucins [11. (MC) Human intestinal sulfated glycoprotein [22] (MC) Human lysozyme (PC) Human CEA (PC) Humau pcpsinogen 1I (PC) Serotonin (5-HT) (MC) N-terminal human gastrin 34 (PC)

Dilution

Source

1/20

P.M. Comoglio, Turin, Italy

2-t1M, 2-12M 1 9-13MI, 58M1 M3-SI-168

115,000

P. Burtin, Villcjuif, France

1/16,000

P. Burtin

A099 A t 1B R248 YCS/HLK AC90

1t 2,000 1/2OO 112,000 t I5,000 l/500

R4804 B3t-1 A566

1/2,0iX) 1/2,560 1/300

Dakopatts, Copenaghen, Denmark Dakopatts I.M. Samloff, Scpulveda, CA Serotcc, Oxford, England Cambridge Research Biochemicals, Cambridge, England N. Yanayara, Shizouka, Japan Milab, Malmoe, Sweden Dakopatts

C-terminal pancreatic polypeptide (PC) Human substance P (PC) Synthetic bovine neurotensin (PC) Pure porcine G|P (PC) Porcine gastrin-releasing peptide (PC) Porcine cholecystokinin (PC) Alpha-chain of HCG (MC) Chromogranin A (MC) Synthetic motilin (PC)

221

1/2,000

M.T.T. O'Harc

B45-1 B44-1 B35 R-6902

1/320 1/6,000 1/ 1,0(X) 1/500

Milab Milab Milab N. Yanayara

A B01 5E8 Phe 5 M03

1/500 1/5,000 1/ 1,000 1/ 1,000

Porcine insulin (PC) Pure porcine secretin (PC)

B39-1 B33

1/t,00t)

Cambridge Research Biochemicals S. Ghietmi, Brescia, Italy Ortho, Raritan, NJ A.M.J. Buchan, University of British Columbia, Vancouver, Canada Mitab Milab

Porcine C-terminal glicentin (PC) Porcine pancreatic glucagon (PC) Synthetic cyclic (1-14) somatostatin (PC)

1/2,500

matic nuclei (Fig. 2), suggesting an atypical carcinoid (or well-differentiated neuroendocrine carcinoma). Mitotic activity was m o d erate (6 mitoses per 10 HPF), and necrosis was not found. Invasion o f small vessels was detected only focally. The tumor mucus at the apex o f some columnar cells, in the cytoplasm o f goblet cells, and in the glandular lumina stained strongly with both AB and HID. Practically all the cells o f the solid microacinar carcinoid-like areas and about one-third o f the cells in the papillary adenocarcinomatous areas were positive with the Grimelius' procedure. The diazoni u m technique for 5 - H T stained numerous

cells both in adenocarcinomatous and in carcinoid-like areas. The tumor f r o m the third operation had a monophasic architectural pattern, similar to the solid and microacinar areas described in the first tumor, characterized by sheets, nests, and microacini o f rather small polygonal cells with hyperchromatic nuclei and finely granulated eosinophilic cytoplasms. Mitotic figures were 6 per 10 HPF, and t u m o r necrosis was not found. There was no evidence o f AB-PAS and H I D positivity. All the cells were argyrophilic with Grimelius' silver stain (Fig. 3), and about 5% o f t h e m were also positive with the diazonium technique.

Nasal Adenocarcinoma-Carcinoid

Figure 1. Area of typicai moderately differentfated papillary-tubular cylinder cell adenocarclnoma IH&E, x200)

43

Figure 3. Intense and diffuse cytoplasmic argyrophitia in the recurrent ~umor (Grimelius" silver. x4001.

Immunohistochemical Findings

In tumor tissue from the first operation, i m m u n o peroxidase studies for the localization of carcinoembryonic antigen (CEA) revealed positive staining m most areas o f both the adenocarcinomatous and carcinoid components CEA imnlunoreactivity appeared to be concentrated at the apical plasma m e m brane o f t u m o r cells. Both the intracellular arid extracellular mucus within the adenocarcinomatous component showed positive staining for a cotorectal mucin-like antigen (CAR-5) (Fig. 4) with a distribution very similar to the AB and H I D positivity. [mmunostaining for a small intestinal mucin antigen (M3SI) was observed in about 10% o f the goblet cells and m the extracellular mucus Staining for an antigen present in gastric foveolar cells (M1) and lysozyme immunoreactivity were detected in the columnar cells with few apical mucus Exocrlne and Oncofetal Markers

Figure 2, Solid nests ot uniform, small cells in area of typical carcinoid tumor {H&E, x 1001,

droplets and in goblet cells. No pepsinogcn II nnmunoreactivity was demonstrated. In t u m o r tissue from the third operarion. no staining was obtained with any of the markcrs e m p l o y e d In tumor tissue from the first operation, about 8{)~ o f celts m the solid carcinoid-like areas were positively stained for chromogranin A, 20% for gastrin 34, 2{)% for 5-HT. 10% for somatostatin. 5% for glicentin, and tess than l % for PPct, alpha-chain o f human chorionic gonadotropin and pancreaticspecific glucagon. In the papillary and tubular adenocarcinomatous component, the N E cell types present were both 5 - H T (Fig, 5) and chromogranin A l m m u n o r e a c rive. No other immunoreactivities were Neuroendocrlne Markers

Figure 4. CAR-5 immunoreact~vity present over the luminal surface of columnar adenocarcinomatous cells (immunoperoxidasehematoxylin, • 400).

44

Endocrine Pathology

Volume 4 Number I

March 1993

Figure 5. Seroton~n-=mmunoreactive cells w~thin glandular structures (immunoperox~dasehematoxylir x400).

detected with the remaining antisera or antibodies employed. In tumor tissue from the third operation, about 80% o f the cells were i m m u n o reactive for chromogranin A, 20% for 5HT, 10% for somatostatin, and less than 1% for gastrin 34 and glicentin.

Figure 6. Electron microscopy of the apical part of tumor cells in a tubule. Abundant m=crovilti typ