Non-Hodgkin’s lymphoma of the hard palate P. Blot?. M.D.. L. \utz Delden, Atttstcrd~m, The Netherlands PATHOLOGIC
INSTITUTE,
FREE
M.D.,
and 1. van der Waal, D.D.S.,
UNIVERSITY
In the past decades many changes have taken place in the classification of lymphoreticular malignancies. At present two main groups are recognized-Hodgkin’s lymphomas and non-Hodgkin’s lymphomas. Hodgkin’s lymphomas rarely affect the oral cavity. The mouth, especially the soft tissues, is somewhat more frequently involved in cases of non-Hodgkin’s lymphoma. There seems to be some predilection for the mucosa of the palate. The present report describes eight patients in whom a swelling of the palatal mucosa led to the diagnosis of non-Hodgkin’s lymphoma. The emphasis is on the clinical and microscopic aspects. The present most accepted histologic classifications have been applied and are briefly discussed.
I
n 1975 Tomich and Shafer’ reported twenty-one cases of so-called lymphoproliferative disease of the palate and suggested that most, if not all, of their cases were actually examples of malignant lymphoma. In a series of 1.367 patients with extranodal lymphomas published in 1972 by Freeman and associates,’ about 2 percent were located in the oral cavity. Unfortunately, those oral locations were not specified any further. Lehrer and co-authors:’ reported ten cases of lymphoma in the oral cavity and pharynx, including one case of palatal involvement. In Cook’? series of six patients with oral lymphomas. none was located in the palate. The present report describes eight patients with lymphoproliferative disease of the palate which, indeed, proved to be malignant lymphoma. In the same period six patients were seen with lymphomas in other sites of the oral cavity. three of which were located intraosseousl\ METHODS
AND MATERIALS
In all patients in whom biopsy of the palatal swelling a malignant lymphoma, tomographs of the maxilla were made. In none of them could underlying bone destruction be detected. In five of the eight patient\ a clinical staging procedure was done, comprising mediastinal tomography, bipedal lymphography, bone marrow examination, scintigraphy of the liver and spleen, and needle biopsy of the liver. In treatment, radiation was applied by megavolt techniques. Wholebody radiation has not been used in our patients. Chemotherapy. w;hen used, consisted of COP (cyclorevealed
~X~30~1210.‘70/0501~15+0X$0~1
X0/0
0
1979 The C. V. Mosby
Co
phosphamide, Oncovin, and prednisone) and CHOP (cyclophosphamide, hydroxydaunorubicin, Oncovin, and prednisone). The histologic material was studied with hematoxylin and eosin, periodic acid-Schiff, methyl green-pyronine, reticulin, Giemsa, and naphthol-ASD-chloracetate esterase stains and by electron microscopy, for which purpose in six of the eight patients some tissue was fixed in glutaraldehyde and postfixed in osmium tetroxide. The follow-up period varied from 5 months to 5 years. For all patients a short description of the case history will be given. The most important findings are summarized in Tables I and II. CASE REPORTS CASE 1
In January. 1973, an 80-year-old woman was referred becauseof a rapidly growing ulcerating massof the palate (Fig. 1). She had been aware of a small submucosalnodule in the palate for some years, but this had never caused her any discomfort. On both sides of the neck multiple hard, indurated, and nonpainful lymph nodes could be palpated. The patient seemedto be healthy otherwise. On the basis of repeatedbiopsies of the palatal mass,the diagnosis of sarcoma (most likely rhabdomyosarcoma)was made.The diagnosis of malignant melanoma was considered hut not accepted hecauseof lack of melanin pigment and a negative DOPA test result. Because of the rapid growth of the tumor, it was decided not to wait for the result of the electron microscopic examination of the biopsy specimen.The patient was treated by surgery, including cryosurgery. Treatment resulted in a 445
Non-Hodgkin’s lynphoma of hard pulutt~
Volume 47 Number 5
447
Fig. 3. Low-power view of palatal biopsy specimen diagnosed as malignant non-Hodgkin’s lymphoma. (Fo, typing, bee Table II.) Note remnant of salivary gland duct. (Hematoxylin and eosin stain, Original magnification. x65.1
time. Chemotherapy was instituted, resulting in a remission of the sternal tumor. Radiologic examination of the sternum showed a complete healing of the bone defect. Additional radiotherapy, a so-called “iceberg radiation.” was given to the sternal area (3.000 rads in 3 weeks) and was followed by more chemotherapy. In July. 1978. the patient was doing well and was apparently free of disease. CASE 5
In April, 1977, an 84-year-old man was referred because of a rapidly growing swelling of the palatal mucosa of about 3 weeks’ duration (Fig. 9). The medical history was essentially negative. Extraoral examination did not reveal any abnormality. A biopsy of the oral lesion led to the diagnosis of malignant non-Hodgkin‘s Iymphoma. Because of the age of the patient. no additional uork-up had been done and ra-
diotherapy was instituted immediately. At the end of the radiation course, 4 weeks later. the palate had almost regained a normal aspect. Eleven months after his first admission the patient suddenly died. A few days earlier. tumorous involvement of the liver had been diagnosed on the basis of clinical and scintigraphic examination findings. Permiahion for autopsy was refused. (Henefer and associates” described a case of palatal enlargement in a 65-year-old man with chronic lymphocytic leukemia which clinically looked much like the present case.) CASE 6
A X&year-old man was referred because of a swelling of about 2 months’ duration in the right hard palate in the molar area. Under the provisional diagnosis of pleomorphic adenoma, an excisional biopsy was performed in September, 1977.
Fig. 4. Ht.&power
Lie\\
bq ;I monotonous
of matenul
population
sho\+n
of lymphoid
Fig. 5. Electron
microscopic
\ic’w
11 mphoid
cells
\vith
condensation
(Original
magnitication.
variable
* 1.100
in FIN. 3. demonstrating cells.
01 mallgnant 1
Hematoxylin
non-Hodpkin’s
01‘ nuclear
chromatin.
the remaming
and eosin
Iymphoma Note
stain.
salivary Original
~hou.11 in Figs. the moderately
gland
dt~ct \tlrr~lundcc!
magnitication.
3
and
irrqular
1.
35)
&mc~~~~tIatin~
nuclear
(,utlinc\
/
Volume Number
Fig. 6. High-power view of lymphoid cells shown in Fig. 5. Note the clearly visible different content (91’ condensed chromatin. There is distinct maturation dissociation of cytoplasm and nuclei. almost conclusive (‘1. malignancy. (Original magnification, X 15,000.) at another institution (Fig. IO). Surprisingly, the microscopic examination revealed a malignant non-Hodgkin’s lymphoma. There was one suspicious submandibular lymph node on the left. Additional staging did not disclose any abnormality in this otherwise healthy patient. The palatal wound, in the meantime, had healed nicely. Nevertheless, radiotherapy was given to the upper jaw, also including the cervical nodes. In July, 1978, the patient was doing well and was apparently free of disease. CASE 7 In October. 1977. a 47.year-old man was referred by his dentist hecause of a palatal swelling in the left molar area. The dentist had made a tentative diagnosis of periodontal abscess and had incised the lesion (Fig. I I). No drainage occurred. however. Biopsy of the lesion in this otherwise apparently healthy patient revealed malignant non-Hodgkin’s lymphoma. Because of the alarming speed at which the tumor seemed to grow. radiotherapy was started immediately, without awaiting the results of the additional staging procedures. After 2 weeks, the laboratory results disclosed that the patient actually suffered from disseminated malignant lymphoma. Chemotherapy was given in addition. In July, 1978, the patient was doing well and was apparently free of disease. He is still on a chemotherapeutic regimen. CASE 8
In February. 197X, a 36-year-old woman was referred by her dentist because of a gradually increasing swelling of the
Fig. 7. Case 3. Swelling of the right Grlc of the r,tlate in
;I
26-year-old man. There is also some s~cll~ng at the Icft \idc. The dentist considered an odontogenic cauw ;tntl cxtractcd the second molar.
palatal mucosa on the right (Fig. 12). She had complained 01 recurrent gingival swellings in both upper and lov\L~rjab+\ for about 15 years. Several gingivectomics had been j~crformed in the past. She was not taking mcdicamcnts and II;,\ apparently healthy. Biopsy specimens of multiple areas \~crc taken from both the maxilla and the mandible. Only the material from the palatal mucosa proved to bc positive for a malignant non-Hodgkin’s lymphoma. Additional vvorh-up did not reveal other foci. Radiotherapy had been applied III the qy~t~ jan.
Table I. Clinical non-Hodgkin’s
data of eight lymphoma
patients
with
of the palate
F
1: 41 I, I1
11 21 f
Discussion Thtw caxs
vxmh
fo
2s cutranodal
ha\ c not
originated
be justification lymphomas from
tot- conaidtzring in the hard
Waldeycr’s
ring
palate
our which
01‘ faucio-
tics.’
’ As can hcl seen in Table
from
low-grade
and
the
II. ti\c
remuinin
high-grade Tumors
Iymphomas. that can be mistaken
malignant
non-Hodgkin’s
malignant
melanoma,
anaplastic
from
mtcroscq~icall~
lymphoma
include
carcinoma.
and pri-
tologic
Lor differentiation of a lymphoma 2(riven by Saltr.stein” from a reactt\c process. In the absence of germinal ccnterx. the lw1ymorphic nature ot’ the cellular iw liltrate. includtng apparently normal lymphocytes. rc’-
or on its immunologic
charactcri\-
histologic
for primaq
mary
appt‘arance’i
Valuable
sutfcrtd
patients
pharyngcal
Iymphoid tissue. \vhich is part of the “1ynphatic structuw.” The classification of non-Hodgkin’s lymphomas t\ controversial and can be based either soleI) on its hi\-
chemodectoma.
patients
g three
criteria
arc
Volume 47 Number 5
Fig. 11. Case 7. Swelling of the left side of the palate. The dentist thought of a periodontal abscess and incised the lesion. No drainage occurred. however. A biopsy revealed the true nature of the lesion.
Table II. Histologic
typing
of 8 patients with non-Hodgkin’s
Ruppaport”
I 2 3 4 5 6 1
8
Fig. 12. Case 8. Diffuse swelling of the right side of the palate and maxillary ridge.
lymphoma
Lukes and Collins’
of the Lennrrt et al
i-
Hiatiocytic (?) Diffuse, well-differentiated lymphocytic Histiocytic (?)
Immunoblastic sarcoma(‘?) B-cell plasmacytoid lymphocytic
Immunoblastic sarcoma(‘3 Immunocytoma
High 1.ow
T-cell convoluted lymphoblastic
High
Diffuse. well-differentiated lymphocytic Diffuse. poorly differentiated histiocytic Nodular lymphocytic histiocytic Diffuse, poorly differentiated lymphocytic Diffuse. well-differentiated Iymphocytlc
B-cell plasmacytoid lymphocytic
T-cell convoluted lymphoblastic lymphoma (‘?) Immunocytoma Centroblastic
High
Centrocytic-centroblastic
I .ow
Centrocytic-centroblastic
i.OU
lmmunocytoma
!,OW
B-cell large noncleavedfolliculal center cells B-cell small cleaved follicular center cells B-cell small cleaved follicular center cells B-cell plasmacytoid lymphocytic cells
active histiocytes, and inflammatory cells is most suggestive of a pseudolymphomatous process, while the presence of follicular center cells (centrocytes and centroblasts) outside a normal germinal center favors a malignant lymphomatous process. An immunofluorescence-immunoperoxidase technique, showing either a polyclonai or monoclonal character of the lymphomatous growth. can also be of great help. Especially on the palate, Wegener’s granulomatosis should be included in the differential diagnosis. It is important to know that Wegener’s granulomatosis is characterized by an angiocentric and angiodestructive Dolvmoruhous atvuical Ivmphoid infiltrate with plasma
! .ou
and Shafer’ have extensively discussed those aspects in their previously mentioned article. In order to get maximum information from the biopsy and to avoid diagnostic difficulties as much as possible, it is mandatory to handle the specimen as gently as possible. Depending on the pathologist’s preference, the tissue should be sent in irnmcdiately. fresh or in a special medium. The pathologist will then have a chance to make touch preparation\ for cytologic examination and to apply techniques of enL!me histochemistry and electron microscopy as well. Summary
Mahgnant Lqmphoma I” the @dt Cavit) tinn‘.. OP.&I 41: 341.450, 1976. Cook, H. P : Oral Lymphomaa. 01141 .SI~K(,. fJ: hUtI-70.i. 1961. Moran, fz. M.. Ultmann, J. E.. Ferguson. D. J . tlollcr. 1’ 13.. Ranninger. K.. and Rappaport. H.: Stagins Laparotom> 111 non-Hodgkin’s Lymphoma, Br. J. Cancer 31: Suppl 2. XX236, 1915. Rappaport. H.: Tumors of’the Hematopoletlc Sjstt’m l/i Atis\ 01 Tumor Pathology. Section Ill. Faacrcle X. Washington I) (‘ 1966. Armed Forces Institute of Pathology. Lukes. R. J.. dnd Collins, R. 0.: Immunologic C‘llaracturl/,itl~~t! of Human Malignant Lymphomaa. Cancer 34: 13X%I.S(!3. 1974. Lennert. K.. Stein. H.. and KuscrIIng. 1, C’ytologlial lu~(! Functional Criteria for the Classification ot Malignant f.\ I+ phomata. Br. J. Cancer 31: Suppl 2. 2Y-li. 1075 Henet’er. f< P Nelson. J F.. and Beaupr