Two unrelated clonal chromosome rearrangements in a nasal papilloma

Two Unrelated Clonal Chromosome Rearrangements in a Nasal Papilloma Yue-sheng Jin, Sverre Heim, Nils Mandahl, Anders Bi6rklund, Johan Wennerberg, Roger Willen, and Felix Mitelman

ABSTRACT: We have cytogenetically examined short-term cultures from a nasal papilloma, a tumor type in which chromosome aberrations have hitherto not been reported. Two pseudodiploid clones were detected, giving the tumor karyatype 46.XY,t(~ ;3)(p31 :p121,'46,XY.t(1 ~:?](q25;?).

INTRODUCTION Because of the technical difficulties involved, little is known about the c h r o m o s o m e abnormalities in most human solid tumors [1, 2]. Cytogenetic studies of primary tumors from the upper aerodigestive tract are restricted to only four squamous cell carcinomas [3-6]. We present here the cytogenetic findings in a nasal papilloma. The karyotype of this benign tumor included two apparently unrelated clonal chromosome abnormalities.

CASE REPORT The patient, a 57-year-old male, was admitted to the Department of Oto-RhinoLaryngology because of recurrent right-sided nasal polyposis. He was operated on with a lateral rhinotomy. The maxillary sinus was filled with papillomatous tissue, wh i ch was exenterated. Histopathologic examination revealed a papillomatous tumor outlined by cylindrical transitional epithelium that proliferated inversely into an edematous stroma (Fig. 1). The basal membranes were always intact; no infiltration was detected. Proliferation of reserve cells in combination with squamous cell metaplasia up-lifted the ciliated cells. Some mitoses were seen, but there was no cellular atypia. In some areas intercellular cystic spaces were found, giving the tissue a " m o t h - e a t e n " appearance (Fig. 2). Incarcerated goblet cells were also present. The stroma was edematous with moderate infiltration of inflammatory cells. The picture was thus typical for a transitional-type papilloma [7].

From the Departments of Clinical Genetics (Y. 1.. S. H., N. M., F. M.), Oto-Rhinu-Laryngol.gy{A. B.. ]. W.) and Clinical Pathology {R. W.). Lund Uniw;rsity llospital, I,und, Sweden. Address reprint requests to: Dr. Y. Jin, Department of Clinical Genetics, University Hospital, S-221 85 Lund, Sweden. Received luly 28. 1988. accepted December 14, 1988.

29 1989 Elsevier Science Publishing Co., Inc. 655 Avenue of the Americas. New Ynrk, NY 10010

Cancer Genet Cytogenet 39:29 34 (1989) 01(15-460889$03.50

30

Figure 1 Overview of the papillomatous tumor demonstrating inv(~rse proliteralion ot transitional epithelium with reverse (:ell hyp(.'rplasia, squamous metaplasia, and remainillg (.:ohinHu~r epithelium (H&E ×12}. Figure 2 Higher magnification demonstrating transitional type epithelium with in(:ar(:erated goblet (:ells and inter(:ellular rout:in-filled spaces (H&E x47).

31

I

I

I

~ x

,-°

.c

o

0

IL2

I,o 4

I

N

I x

o

I

oil., ©

p,,

I

X "5 ~r

~s 5r -

I

I I

y?

_

I

W Q

I

~

m

°~

Figure 4

19

~o

13

6

1

9

Ir

21

16

-'~.,

10

tr

17

22

"

11

".,,

4

18

z,~

12

X Y

Ii

~;--

5

Representative karyotype demonstrating the clone 46,XY,I(1:3)(p31 ;p12). Arrowheads inclic:ate br~akpoints.

20

15

.~-x

OIt

14

8

I(

,,¢

7

3

2

4

Ix3

Rearrangements in Nasal Papilloma

33

CYTOGENETIC STUDIES The procedures for processing epithelial tumor biopsies for chromosome analysis have been described in detail elsewhere 13]. In brief, the fresh tumor sample was minced, disaggregated overnight in a collagenase solution, and plated in Flaskettes in RPMI-1640 m e d i u m with Hepes buffer supplemented with fetal calf serum, glutamine, antibiotics, insulin, cholera toxin, and epidermal growth factor. After 1 week, in situ preparations were made by colcemid exposure, hypotonic treatment in 0.3% NaCl, and fixation in methanol/acetic acid. Before banding with Wright stain, the slides were incubated overnight at 60°C. A total of 32 metaphases were photographed and karyotyped. All cells were pseudodiploid. Twelve cells had nonclonal chromosome abnormalities. In the rem a i n i n g metaphases, two abnormal clones were found, 46,XY,t(ll;?)(q25;?) in 11 cells (Fig. 3) and 46,XY,t(1;3)(p31;p12) in nine cells (Fig. 4).

DISCUSSION Because cytogenetic abnormalities have not previously been reported in papilloma, no data from similar tumors are available for comparison with the aberrations found in the present case. To the best of our knowledge, t(1;3)(p31;p12) has not been described in other neoplasms. On the other hand, the band 11q25 is frequently rearranged in various types of neoplasia [21, with formation of a t(1 ~1;?)(q25:?) marker in 13 cases (four acute T-cell lymphocytic leukemias, four malignant lymphomas, one acute monocytic leukemia, one acute nanlymphocytic leukemia, one plasma cell leukemia, one small cell carcinoma, and one adenocarcinoma of the lung). Whether any of these markers were identical to the one described here is impossible to say. Future cytogenetic investigations of additional nasal and laryngeal papillomas will clarify whether any consistent pattern of karyotypic abnormalities characterizes these benign tumors and whether unrelated chines will be an equally characteristic feature of papillomas as they have proved to be in several squamous cell carcinomas [3-5, 8, 91. This work was supported by grants from the Swedish Cancer Society, the Swedish Work Environment Fund, and the JAP Foundation for Medical Research. Dr. Jin is on leave from the Department of Genetic:s, Cancer Institute, Sun Yat-sen University of Medical Sciences. Guangzhou, People's Republic of China.

REFERENCES 1. Heim S, Mitelman F [1987]: Cancer Cytogenetics. Alan R. Liss, Inc., New York. 2. Mitehnan F (1988): Catalog of Chromosome Aberrations in Cancer, 3rd Ed. Alan R. Liss, Inc.. NY. 3. Jin Y, Mandahl N, Helm S, Biorklund A, Wennerberg l, Mitelman F (1988): Unique karyotypic abnormalities in a squamous cell carcinoma of the larynx. Cancer Genet Cytogenet 30:177-179. 4. Jin Y, Mandahl N, Heim S, Bi6rklund A, Wennerberg J, Mitelman F (1988): t(6;7)(q23;p22) as the sole chromosomal anomaly in a vocal cord carcinoma. Cancer Genet Cytogenet 32:305307. 5. Jin Y, Heim S, Mandahl N, Biorklund A, Wennerberg ], Mitelman F (1988): Multiple apparently unrelated clonal chromosome abnormalities in a squamous cell carcinoma of the tongue. Cancer Genet Cytogenet 32:93-101. 6. Teyssier JR (1987}: Nonrandom chromosomal changes in human solid tumors: Application of an improved culture method. J Natl Cancer Inst 79:1189-1198.

34

Y. Jin el ~tl.

7. Friedmann 1, Osborn DA {1,q82): Pathology of the (;ranulomas and Neoplasms o[ the Nost, and Paranasal Sinuses. Churchill Livingstone. l,andon, pp. 105-116. 8. Heim S, lin Y. Mandahl N. Biorklund A. Wennerberg l, Jonsson N. Mitelman I-' (1988): Multiple tmrelated clonal chromosome abnormalities in an in situ squamnus cell car(.immm of the skin. Cancer (;enet Cytogenet 36:149-153. 9. Heim S. Mertens F. Jin Y. IVlandahl N. Iohansson B. BiOrklund A. Wennerberg J. Ionss(m N. Mitclman F (1989}: l)iverse chromosome abnormalities in squamous cell carcinomas c~f the skin. Cancer (;enet Cytogenet 39:69-76.