Polymorphic reticulosis: A reappraisal

Polymorphic Reticulosis: A Reappraisal JOHN G. STRICKLER, MD, MANUEL F. MENESES, MD, THOMAS M. HABERMANN, MD, DUANE M. ILSTRUP, MS, JOHN D. EARLE, MD, THOMAS J. MCDONALD, MD, KAREN L. CHANG, MD, AND LAWRENCE M. WEISS, MD studied 18 patients (15 men and three women) evaluated for a destructivesinonasallesion that had been diagnosedas “polymorphic reticulosis.”The histologicfeatures of each lesion were those of “angiocentric immunoproliferative lesions,” characterized by atypical lymphoid infiltrateswith polymorphous, angiocentric, and necrotic features; 13 were grade 2 and five were grade 3. The neoplastic cells in each patient had a T-cell phenotype. Epstein-Barrvirus RNA was detected in the neoplastic cells of 17 of the 18 T-cell lesions. Initial treatment consisted of local radiation therapy in each patient, chemotherapy in two patients, and prednisone in another patient. Two patientswere lost to follow-up and the other 16 had a median followup of 14 years, 2 months (range, 4 months to 32 years, 5 months). Four patients are alive and disease free, four patients died not of diseaseor complicationof therapy,and eight patientsdied of disease. The Kaplan-Meierestimateof survivalwas 63% at 5 yearsand 50% at 15 years. Histologic progressionof angiocentricbnmunoproliferative lesions from grade 2 to grade 3 was observed in two patients, and a correlationbetweenangiocentricimmunoproliferativegrade and survival could not be detected. These data suggest that polymorphic reticulosisis an Epstein-Barr virus-elated angiocentricT-cell lymphoma. HUMPATHOL 25659-665. Copyright0 1994 by W.B. SaundersComPanY

“Polymorphic reticulosis” (PR), also known as midline malignant reticulosis,” is a term introduced by Eichel et al3 to describe aggressive lymphoreticular lesions involving the upper aerodigestive tract or midline facial structures.4 The histologic features of PR are identical to those of sinonasal “angiocentric immunoproliferative lesions” (AILS), which are characterized by angiocentric and angioinvasive lymphoid infiltrates with a wide range of cytologic atypia.5g These histologic features are similar to pulmonary “lymphomatoid granulomatosis.“‘S’2 The clinical features of PR are part of the spectrum of “lethal midline granuloma” or “midfacial necrotizing lesions”, . these terms describe midline destructive lesions caused by various pathologic processes, including PR, lymphoma, Wegener’s granulomatosis, infections, sarcoidosis, and idiopathic midline destructive disease.““’ From the Division of Anatomic Pathology, the Division of Hematology and Internal Medicine, the Section of Biostatistics, the Division of Radiation Oncology, and the Department of Otorhinolaryngology, Mayo Clinic and Mayo Foundation, Rochester, MN; and the Department of Pathology, City of Hope National Medical Center, Duane, CA. Accepted for publication November 15, 1993. KeJiwurds: angiocentric immunoproliferative lesion, angiocentric lymphoma, Epstein-Barr virus, peripheral T-cell lymphoma, polymorphic reticulosis. Address correspondence and reprint requests to John C. Strickler. MD, Mayo Clinic, 200 First St SW, Rochester, MN 55905. Copyright 0 1994 by W.B. Saunders Company

0046-S177/94/2507-0006$5.00/0

Although infectious and immune mechanisms have been proposed,‘324 many investigators postulate that PR is a non-Hodgkin’s lymphoma. Because the lymphoid cells in PR typically are angiocentric and demonstrate a Tcell phenotype,25 PR often is considered to be an unusual form of angiocentric T-cell lymphoma.20,‘““” However, molecular genetic studies have not demonstrated evidence of clonal T-cell receptor gene rearrangements in some cases of PR and nasal ~Ls.9.2R.363R Furthermore, recent studies”.“*3M3 show that the lymphoid cells in PR (nasal AILS) may contain Epstein-Barr virus (EBV) genomes or antigens, suggesting an infectious component to the pathogenesis. Clinical studies are small, incorporate variable diagnostic and staging criteria, use various pathologic criteria, and approach therapy differently.44 This study describes the pathologic and clinical features of 18 PR patients who were evaluated and managed at the Mayo Clinic.

MATERIALS AND METHODS Patient Selection Eighteen patients with PR were studied. The initial clinicopathologic diagnosis of PR was established at the Mayo Clinic between 1957 and 1983 from the histologic assessment of a tissue biopsy specimen of a destructive sinonasal mass. Patients were excluded from this study if clinical information or paraffin-mbedded tissue was not available.

Pathologic Examination The histologic diagnosis of PR was confirmed in the initial biopsy specimen from all 18 patients and in specimens taken at the time of repeat biopsy from seven patients by using criteria established by Eichel et al.” Histologic features of PR, including polymorphous lymphoid infiltrates with angiocentric and angioinvasive features, were identified in each tissue specimen. These histologic criteria for PR are identical to those of AILS, and grading of AILS (grades 1 to 3) was performed by using previously reported criteria:%’ Patients with nonangiocentric large cell lymphoma were excluded from the study. Immunohistochemical studies were performed on paraffin-embedded tissue using standard techniques?’ The phenotype of the atypical lymphoid cells in each case was assessed by using antibodies to leukocyte common antigen (CD45RB; Dako Corp, Carpinteria, CA); the B-lineage marker L26 (CD20; Dako); the T-lineage markers CD3 (polyclonal; Dako) , Leu-22 (CD43; Becton Dickinson, San Jose, CA), and UCHL 1 (CD45RO; Dako); and the natural killer marker Leu-‘7 (CD57; Becton Dickinson).

HUMAN

PATHOLOGY

Volume 25, No. 7 (July 1994)

lineage (CD20, LX) or T-lineage (CD43, Leu-22) antigens. Immu~~ohistochemical studies for the EBV latent membrane protein-l (LMP-1, Dako) also were performed using standard techniques.

RESULTS Pathological Findings Twenty-five biopsy specimens were studied from including 18 initial specimens and the 18 patients, seven relapse specimens. All specimens showed histologic features of PR. The atypical lymphoid infiltrate

FIGURE 1. Polymorphic reticulosis consists of a lymphoid infiltrate that is angiocentric and angioinfiltrative. (Original magnification x250.)

Epstein-Barr Virus Studies Epstein-Barr virus RNA was detected by in situ hybridization (ISH) in paraffin-embedded tissue with a biotinylated 30-base oligonucleotide that is complementary to EBERl, a region of the EBV genome that is actively transcribed in latently infected cellsx,“” The specificity of this technique for EBV detection has been confirmed previously using RNAase predigestion, competitive inhibition, and control probe studies.‘” Tissues without evidence of EBV RNA were tested for viability of total RNA with a polydeoxythymidylic acid [poly d(T)] probe.47 Double-labeling studies were performed by combining ISH for EBV with immunohistochemistry for B-

was angiocentric, angioinfiltrative, or both, often invaded cartilage and bone, and commonly was associated with extensive necrosis and mucosal ulceration (Fig 1). The polymorphous lymphoid infiltrates were characterized by a spectrum of cell sizes and cytologic atypia, and were associated with plasma cells, eosinophils, and histiocytes (Fig 2). The histological features closely resembled those of peripheral T-cell lymphomas found in other sites. Each biopsy specimen also showed histological features of AILS because atypical lymphoid infiltrates with polymorphous, angiocentric, and necrotic features were identified in each case. Grade 2 AILS (13 initial biopsy specimens) consisted of a polymorphous lymphoid infiltrate with atypia in the small lymphoid cells. Grade 3 AILS (five initial biopsy specimens) consisted of a monomorphous population of large atypical lymphoid cells that were associated with prominent necrosis. Immunohistochemical studies of the initial biopsy specimens revealed that the atypical (large) lym-

FIGURE 2. The polymorphous infiltrate includes lymphoid cells with a spectrum of cell sizes and cytologic atypia. (Original magnification x400.)

POLYMORPHIC

RETICULOSIS

(Strickler et al)

phoid cells had a T-cell phenotype (CD3+, CD43+, CD45RO+, CD20-) in all 18 patients. These 18 cases contained few reactive B cells (CD20+) and showed morphological features that resembled peripheral Tcell lymphomas. The lymphoid cells in each specimen did not react with the natural killer marker Leu-7 (CD57).

Epstein-Barr Virus Studies In situ hybridization studies detected EBV RNA in the atypical (large) lymphoid cells of 17 of 18 T-cell lesions, including grade 2 (12 of 13 cases) and grade 3 (five of five cases) AILS. Each of the seven lesions that were positive for EBV and recurred also contained EBV genomes in the recurrence specimen. The cells that were positive for EBV showed intense nuclear staining in the majority of the lymphoid cell population and included large lymphoid cells with cytologic atypia and angiocentricity (Fig 3). Double-labeling immunohisto chemical and ISH studies (Fig 4) confirmed that the EBV-positive lymphoid cells had a T-cell phenotype (CD43+, CD20-). In situ hybridization studies did not detect EBV RNA in one T-cell lesion (grade 2 AIL), although adequate RNA was demonstrated by poly d(T) studies. Evidence of EBV LMP was detected by immunohistochemical studies in only three T-cell lesions (patients no. 1, 3, and 12), despite appropriate staining of

FIGURE 4. Double-labeling studies demonstrated that the lymphoid cells that stain positively for EBV black are positive for CD43 (brown). (Original magnification x400.)

Reed-Sternberg cells in control cases of known EBV-as sociated Hodgkin’s disease.

Clinical Data

FIQURE 3. In situ hybridization studies demonstrate that the angiocentric lymphoid infiltrate consists of cells that stain positively for EBV, as indicated by intense nuclear reactivity (black). (Original magnification x 160.)

Table 1 summarizes the clinical features of the patients. There were 15 men and three women with a median age of 45 years (age range, 22 to 80 years). The sites of the initial biopsy specimens included the nasal cavity in 13 patients, the nasopharynx in four, and the larynx in one. Initial therapy consisted of local radiation in each patient, chemotherapy in two, and prednisone in one. Recurrent disease was treated with additional local radiation therapy and chemotherapy (two patients) or additional chemotherapy alone (five patients). The sites of relapse included local recurrence (both within and outside the radiation field) in six patients and systemic disease (including lungs and skin) in three patients (Table 1). The elapsed time from diagnosis to relapse ranged from 3 months to 18 years. Serial pathologic specimens (seven specimens) usually showed similar histologic features and AIL grades. However, histologic progression from grade 2 to grade 3 AIL was observed in two patients: patient no. 2 (12 years, 11 months after diagnosis) and patient no. 8 (2 years, 11 months after diagnosis). Two patients were lost to follow-up (patient no. 7 at 5 months and patient no. 17 at 8 months). The other 16 patients had a median follow-up of 14 years, 2 661

HUMAN

TABLE 1. Initial

Patient

Biopsy

Age

No.

Year

(yr)

sex

1957

48

F

1

Biopsy

Site

Volume 25, No. 7 (July 1994)

PATHOLOGY

Clinical Data From Patients With Polymorphic AIL

EBV

Grade

ISH

Nasal cavity

2

+

(left)

Reticulosis’

Initial Initial XRT

Treatment

Subsequent

Response

Follow-up

Treatment

Relapse

Duration

CR

38 Gy (left

Dead.

and

of Survival

not of di.xase

nasal cavity,

or complication

sinuses)

therapy

of

(2Y yr, 3

“lo) 2

1958

53

M

Nasal cavity

2

+

XRT

CR

17.75 Gy

XRT

(nasal cavity,

(septum)

nasopharynx)

progression AJL grade (lZyr,

3

1959

44

M

Nasal cavity

2

+

XRT

30 Gy (nasal

to 3

11 mo)

30.56 Gy;

Dad,

disease:

tincristine,

conlirmrd

prednisone.

mo)

automy (is,,

Dead,

not of disease

or complication therapy

4

1960

48

M

Nasopharynx

2

+

XRT

2

procarbazine

CR

CWity)

(=ptut”)

systemic

cyclophosphamide,

CR

54 Gy

(nasopharynx)

Local

recurrence

mo) Dead of disease

Cyclophosphamide, vincristine,

(18~)

of

(21 yr, 5

(I8

F7. 9 mo)

prednisone, doxorubicin

(1

cycle) 5

1960

41

M

Nasalcavity

3

+

b=ptum) 6

1970

46

F

XRT

33 Gy (nasal

CR

Alive,

cavity)

Nasophaty”x

2

+

XRT

disease

free

(32

yr, 5 mo)

45 Gy (nose,

NA

Local

recurrence

Dead,

Cyclophosphamide,

not of disease

sinuses,

(nasopharynx)

prednisone,

or complication

nasopharynx.

(13 mo)

azathioprine,

therapy;

bronchus,

hepatitis

prednisone

mediastinum);

of

fatal (2 yr, 6

mo)

cyclophosphamide (oral) 7 8

1971 1971

59 80

M M

cavity b-b+)

2

Nasal

+

XRT

NA

38 Gy (right

nasal cavity)

Nasal cavity

2

+

1973

43

M

CR

Cyclophosphamide

1973

52

M

recorrrnce;

turbinate)

(NR);

XRT

progression

+

33 Gy

1973

37

M

XRT

AIL

40 Gy (nasal

NR

cavity)

Nasal cavity

2

+

2

_

(septum) 11

Bleomycin,

prednisone

(=pt”m) 10

Local

(oral)

2

XRT

Lost to follow-up

grade

XRT

30

;

to 3 (2

yT* 11 mo) Relapse, skin (3

Gy (NR) cyclophosphamide

XRT

Dad.

1974

44

M

autopsy

mo) Alive, disease

CR

(4

free

(18

yr,

39 Gy

3 mo) Dead, not of disease

CR

or complication

52 Gy (neck

therapy;

nodes) 12

systemic

disease;

d 1.5)

(“asopharynx) ; XRT

3 mo)

prednisone Cyclophosphamidr

Wity)

Nasopharynx

Dead of disease (3 yr,

vincristine,

(died

mo)

40 Gy (nasal

(5

mo)

(right

Nasal cavity

Qclophosphamide

recllrrencr

(5 mo)

(nasal cavity) 9

Local

of

grade

astrocytoma

4

(17 yr,

3 mo)

Nasalcavity

+

3

Prednisone XRT

CR

(NR);

Dead of disease

36.4 Gy

( 13

yr. 4 mo)

(nasal cavity) 13

1975

73

M

Nasal

cavity

+

3

XRT

40 Gy (nasal

PR

Relapse,

hmg

Dead,

systemic

disease;

(10 mo)

CWity)

pulmonary

involvement; autopsy 14

1977

38

M

Nasal

cavity

2

+

XRT

49 Gy (nasal

CR

Alive,

CWity)

1.5

1978

56

M

Nasal cavity

3

+

XRT

free

(14

free

( I4

yr, 5 mo)

44 Gy (nasal

CR

Alive.

C&T)

(tight

(10 mo)

disease disease

F, 3 mo)

inferior turbinate) 16

1980

22

M

Larynx

3

+

XRT

40 Gy (laynx)

NA

Relapse,

long

Dead

of disease;

pulmonary involvement; for 17

1981

26

M

Niisophaynx

+

2

XRT

50 Gy (nasal

CR

Local

recwrence

cavity, sinuses)

Cyclophosphamide.

Dead

vincristine,

1r

FUO

(10 mo)

of disease

(2 ye.

6 mo)

prednisone, doxorubicin

(1

cycle) 18

1983

32

F

Nasal cavity

+

2

XRT

50 Gy (nasal

CR

Lost to follow-up

cavity, sinoses) Abbreviations:

CR, complete

* Immunohistochemisq

response;

indicated

FUO,

a T-cell

fever

phenotype

of unknown

origin;

(8

mo)

NA, not available;

NR, no response;

PR, partial

response;

XRT,

radiation

therapy.

for all patients.

months (range, 4 months to 32 years, 5 months). Four patients are alive and disease free up to 32 years, 5 months after diagnosis. Four patients died not of disease or complication of therapy, including one patient with hepatitis not related to lymphoma and one patient 662

with a grade 4 astrocytoma. Eight patients died of disease (range, 4 months to 18 years, 9 months), and four of these patients had a systemic lymphoproliferative disorder at the time of death. The Kaplan-Meier estimate of survival in the overall group was 63% at 5 years and

POLYMORPHIC

RETICULOSIS

50% at 15 years. Survival for grade 2 AIL patients (65% at 5 years) was not significantly different from survival for grade 3 AIL patients (60% at 5 years) (P = .77, logrank test).

(Strickler et al)

tric T-cell lymphomas from US patients, which has not been previously reported. However, angiocentric lymphomas in various sites in Asian and Western (nonAsian) patients may contain EBV, which can be demonstrated by using various molecularx~“~3”3g~4’43*5g~60 and immunologic techniques.37,4”’ It has been reported8 that EBV RNA was usually present in the neoplastic cells of grade 3 AILS and typically absent from grade 2 AILS. However, the current study demonstrated EBV RNA in both grade 2 and 3 AILS. Evidence of expression of EBV LMP was found in only three of 18 patients (17%). This low percentage contrasts with the uniform detection of LMP in all seven of the nasal T-cell lymphomas in the series reported by Kanavaros et a1.4’ The significance of our results needs to be tempered by the fact that our detection was performed on paraffin sections. The antibodies to LMP are best applied to frozen sections, although the majority of specimens of EBV-associated Hodgkin’s disease (including the control cases in the current study) have been shown to stain positively with antibodies to LMP in paraffin sections. 6’ It is possible that lower levels of LMP are present in these cases than are present in Hodgkin’s disease cases. The incidence of LMP positivity varies among the various EBV-positive neoplasms. Although LMP is detectable in most cases of EBV-associated Hodgkin’s disease, Vi it is observed in only up to 65% of cases of nasopharyngeal carcinoma and is absent in Burkitt’s lymphoma. Hamilton-Dutoit and Pallesen63 detected LMP in eight cases (10%) of T-cell lymphoma, and Su and Hsieh ’ cited an unpublished study by Chen and colleagues performed in 1991 that found LMP expression in four cases of T-cell lymphoma. However, Harabuchi et a14i were able to demonstrate EBV nuclear antigen-2 in their cases of nasal T-cell lymphoma; EBV nuclear antigen-2 expression tends to correlate inversely with LMP expression. We conclude that PR of the upper aerodigestive tract is an EBV-positive angiocentric T-cell lymphoma. Our study provides further evidence that various benign and malignant T-cell populations may contain EBV genomes.R~g~37~3A~41~42~5g~60~63-68 Although the median survival in this series was more than 14 years, PR (sinonasal angiocentric lymphoma) caused the deaths of eight patients; in four of the eight systemic lymphoma had developed. More advanced and complete approaches to staging may better identify those patients in whom sys temic lymphoma will develop.

DISCUSSION The etiology of PR has been under scrutiny since the initial description by Eichel et al3 in 1966. Although these investigators recognized that PR was locally aggressive and potentially lethal, they recommended the use of this descriptive term until the exact nosology of the process could be determined. Subsequent reports suggested that PR might be an extranodal lymphoma; our study provides additional evidence to support this hypothesis. First, the morphologic features of PR closely resemble the histologic features of an iocentric T-cell lymphomas in other locations.20.‘6.27.8.-35 Second, evidence of clonality has been demonstrated in many cases of PR and AILS by EBV clonality studies.“X3G3’3” Finally, PR has clinical characteristics of an extranodal lymphoma because PR can respond to local radiation therrelapse outside the treated field,‘7.‘“.44.**50 apy, 28~44*4~50 respond to systemic chemotherapy,‘**44~4s~50~5’ or cause death by local recurrence or progression to systemic lymphoma_‘7.‘&44.4~~~Th ese data suggest that PR is an angiocentric lymphoma of the upper aerodigestive tract. Some researchers have proposed5-’ that PR and lymphomatoid granulomatosis of the lung are more accurately designated as AILS rather than as angiocentric lymphomas, reserving the term “lymphoma” for grade 3 AILS. However, we were unable to detect a difference in length of survival between grade 2 and grade 3 lesions in our PR patients. Furthermore, histological pro gression from grade 2 to grade 3 AILS was observed in two PR patients (3 years and 13 years after diagnosis), suggesting that all cases of PR of AIL grade 2 or 3 are best described as angiocentric lymphoma. Like peripheral T-cell lymphomas occurring at other sites, the T-cell angiocentric lymphomas in the sinonasal region are difficult to classify precisely using the Working Formulation.5’ They are often grouped with the diffuse mixed or large cell lymphomas.““’ The small minority of sinonasal angiocentric lymphomas with possible B-cell phenotypes are usually classified as diffuse large cell lymphoma by the Working Formulation.53.54 In contrast, previous studies of nonangiocentric sinonasal lymphomas from patients in the United States and Europe showed that the majority of lesions are large cell or immunoblastic lymphomas with a B-cell phenotype.5557 Previous studie?,42,5R demonstrated that nasal lymphomas can express natural killer markers. Because frozen tissue was not available from any of our patients, accurate assessment of natural killer phenotypes is not possible. However, the lymphoma cells from our patients did not react with Leu-7 (CD57), which marks a subset of natural killer cells in paraffin-embedded tissue. Our ISH studies demonstrate that EBV RNA is present in the neoplastic cells of most sinonasal angiocen-

Acknowkd~t. expert

secretarial

The authors assistance.

thank

Kelly J. Hain

for

REFERENCES 1. Fechner RE, Iamppin DW: Midline malignant reticulosis: A clinicopathologic entity. Arch Otolaryngol95:467-476, 1972 2. Kassel SH, Echevarria FL4, Guzzo Fp: Midline malignant reticulosis (so-called lethal midline granuloma). Cancer 23:920-935, 1969 3. Eichel BS, Harrison EC, Jr, Devine KD, et al: Primary lymphoma of the nose including a relationship to lethal midline granuloma. Am J Surg 112:597-605, 1966 663

HUMAN

PATHOLOGY

4. McDonald TJ, DeRemee RA, Haul-ison EC;, Jr, et al: ‘The pl-otean clinical features of polymot-phic reticulosis (lethal midline granuloma). Laryngoscope 86:93&945, 1976 5. Jaffe ES: Pathologic and clinical spectrum of post-thymir Tcell malignancies. Cancer Invest 2:413426, 1984 6. Jaffe E: “Post-thymic lymphoid neoplasia,” in Jaffe ES (ed): Surgical Pathology of the Lymph Nodes and Related Organs. Philadelphia, PA, Saunders, 1985, pp 218-248 7. Lipford EH, Jr, Margolick JB, Longo DL, et al: Angiocentric immunoproliferative lesions: A clinicopathologic spectrum of postthymic T-cell proliferations. Blood 72:167+1681, 1988 8. Medeiros LJ, Jaffe ES, Chen Y-Y, et al: Localization of EpsteinBarr viral genomes in angiocentric immunoprolifel-ative lesions. Am J Surg Pathol l&439447, 1992 9. Medeiros LJ, Peiper SC, Elwood L, et al: Angiocentric immunoproliferative lesions: A molecular analysis of eight cases. HUM P~~~~~22:1150-1157,199l IO. DeRemee RA, Weiland LH, McDonald TJ: Polymorphic reticulosis, lymphomatoid granulomatosis: Two diseases or one? Mayo Clin Proc 53:634640, 1978 11. l.iebow AA, Carrington CRB, Friedman PJ: Lymphomatoid granulomatosis. HUM PA~‘HOL3:457-558, 1972 12. Stamenkovic I, Toccanier M-F, Kapanci Y: Polymorphic reticulosis (lethal midline granuloma) and lymphomatoid granulomatosis: Identical or distinct entities? Virchows Arch A Path01 Anat Histopathol 390:81-91, 1981 13. Aozasa K, Ohsawa M, Tajima K, et al: Nation-wide study of lethal mid-line granuloma in Japan: Frequencies of Wegener’s granulomatosis, polymorphic reticulosis, malignant lymphoma and other related conditions. lnt J Cancer 44:63-66, 1989 14. Batsakis JC: Wegener’s granulomatosis and midline (nonhealing) ‘granuloma.’ Head Neck Surg 1:213-222, 1979 15. Batsakis JC, Luna MA: Midfacial necrotizing lesions. Semin Diagn Path01 4:90-l 16, 1987 16. Burston HH: Lethal midline granuloma: Is it a pathological entity? Laryngoscope 69: 143,1959 17. McDonald TJ, DeRemee RA, Weiland LH: Wegener’s granulomatosis and polymorphic reticulosis-Two diseases or one? Experience with 90 patients. Arch Otolaryngol 107:141-144, 1981 18. Michaels L, Gregory MM: Pathology of ‘non-healing (midline) granuloma.‘J Clin Path01 30:317-327, 1977 19. Nelson JF, Finkelstein MW, Acevedo A, et al: Midline “nonhealing” granuloma. Oral Surg Oral Med Oral Path01 58:554560, 1984 20. Park m, Yang WI, Lee KG, et al: Histopathological and immunohistochemical studies of polymorphic reticulosis. Yonsei Med J 31~212~218, 1990 21. Pickens JP, Modica L: Current concepts of the lethal midline granuloma syndrome. Otolaryngol Head Neck Surg 100:623-630,1989 22. Tsokos M, Fauci AS, Costa J: Idiopathic midline destructive disease (IMDD): A subgroup of patients with the “midline granuloma” syndrome. Am J Clin Pathol 77:162-168, 1982 23. Crissman JD: Midline malignant reticulosis and lymphomatoid granulomatosis. Arch Pathol lab Med 103:561-564, 1979 24. Eichel BS, Maybery TE: The enigma of the lethal midline granuloma. Laryngoscope 711:1367-1386, 1968 25. Ho FCS, Choy D, Lake SL, et al: Polymorphic reticuiosis and conventional lymphomas of the nose and upper aerodigestive tract: A clinicopathologic study of 70 cases and immunophenotypic studies of 16 cases. HUM PATHOL 21:1041-1050, 1990 26. Chan JKC, Ng CS, Lau WH, et al: Most nasal/nasopharyngeal lymphomas are peripheral T-cell neoplasms. Am J Surg Pathol 11:418429, 1987 27. Chott A, Rappersberger K, Schlossdrek W, et al: Peripheral T-cell lymphoma presenting primarily as lethal midline granuloma. HUM PATH~L 19:1093-1101, 1988

28. Ferry JA, Sklar J, Zukerberg LR, et al: Nasal lymphomd: A clinicopathologic study with immunophenotypic and genotypic analysis. Am J Surg Path01 15:268-279, 1991 29. lshii Y, Ydmanaka N, Ogawa K, et al: Nasal T-cell lymphomas as a type of so-called “lethal midline granuloma.“ Cancer 502336 2344, 1982 30. Lippman SM, Grogan TM, Spier CM, et al: Lethal midline granuloma with a novel T-cell phenotype as found in peripheral Tcell Iymphoma. Cancer 59:936939, 1987

Volume 25, No. 7 (July 1994) 31. Nakdshima T. Inamitsu M, Uemura T. et dl: Immunopatholob~ of polymorphic reticulosis of the larynx. J Lalyngol Otol 103:955-960. 1989 32. Nonwnw’d A, Mdtsubard F, Nakamurd Y, et al: T cell lymphoma pl-escnting clinical and morphological features resembling polymorphic reticulosis and lymphomatoid granulomatosis. Acta Pathol Jpn 33:1289-1301. 1983 33. Ratech H, Burke JS, Blayney DW, et al: A clinicopathologic study of malignant lymphomas of the nose, paranasal sinuses, and hard palate, including cases of lethal midline granuloma. Cancer 64:2525-2531, 1989 34. Yamanaka N, Harahuchi Y, Sambe S. et al: Non-Hodgkin’s lymphoma of Waldeyer’s ring and nasal cavity: Clinical and immunologic aspects. Cancer 56:768-776, 1985 35. Yamanaka N, Kataura A, Sambe S, et al: Midfacial T cell lymphoma: Characterization by monoclonal antibodies. Ann Otol Rhino] Laryngol 94207-21 I, 1985 36. Ho FCS, Srivastava G, Loke SL, et al: Presence of EpsteinBarr virus DNA in nasal lymphomas of B and ‘T’ cell type. Hematol Oncol 8:271-281, 1990 37. Su I-J, Hsieh HC: Clinicopathological spectrum of Epstein-Barr virusassociated Tsell malignancies. Leuk Lymphoma 7:47-53, 1992 38. Su I-J, Hsieh H-C, Lin K-H, et al: Aggressive peripheral T-cell lymphomas containing Epstein-Barr viral DNA: A clinicopathologic and molecular analysis. Blood 77:799-808, 1991 39. Arber DA, Weiss LM, Albujar PF, et al: Nasal lymphomas in Peru: High incidence of T-cell immunophenotype and Epstein-Barr virus infection. Am J Surg Pathol 17:392-399, 1993 40. Furukawa M, Sakashita H, Kimura Y, et al: Association of Ep stein-Barr virus with polymorphic reticulosis. Eur Arch Otorhinolaryngol 247:261-263, 1990 41. Harabuchi Y, Yamanaka N, Kataura A,et al: Epstein-Barr virus in nasal T-cell lymphomas in patients with lethal midline granuloma. Lancet 335:128-130, 1990 42. Kanavaros P, Lescs M-C, Briere J, et al: Nasal T-cell lymphoma: A clinicopathologic entity associated with peculiar phenotype and with Epstein-Barr virus. Blood 81:26882695, 1993 43. Weiss LM, Gaffey MJ, Chen Y-Y, et al: Frequency of EpsteinBarr viral DNA in “Western” sinonasal and Waldeyer’s ring nonHodgkin’s lymphomas. Am J Surg Pathol 16:156-162, 1992 44. Harrison DFN: Midline destructive granuloma: Fact or fiction. Laryngoscope 97:1049-1053, 1987 45. Wat PJ, StricklerJG, Myers JL, et al: Herpes simplex infection causing acute necrotizing tonsillitis. Mayo Clin Proc 69269-271, 1994 46. Chang KL, Chen Y-Y, Shibata D, et al: Description of an in situ hybridization methodology for detection of Epstein-Barr virus RNA in paraffinembedded tissues, with a survey of normal and neoplastic tissues. Diagn Mel Pathol 1:246-255, 1992 47. Weiss LM, Chen Y-Y Effects of different fixatives on detection of nucleic acids from paraffinembedded tissues by an in situ hybridization using oligonucleotide probes. J Histochem Cytochem 39:12371242, 1991 48. Itami J, Itami M, Mikata A, et al: Non-Hodgkin’s lymphoma confined to the nasal cavity: Its relationship to the polymorphic reticulosis and results of radiation therapy. lnt J Radiat Oncol Biol Phys 20:797-802, 1991 49. Liang R, Todd D, Chan TK, et ai: Nasal lymphoma: A retrospective analysis of 60 cases. Cancer 66:2205-2209, 1990 50. Smalley SR, Cupps RE, Anderson JA, et al: Polymorphic reticulosis limited to the upper aerodigestive tract-Natural history and radiotherapeutic considerations. Int J Radiat Oncol Biol Phys 15:599605. 1988 51. Andrassy K, Rasmussen N: Treatment of granulomatous disorders of the nose and paranasal sinuses. Rhinology 27221-230, 1989 52. The Non-Hodgkin’s Lymphoma Pathologic Classification Project: National Cancer Institute sponsored study of classifications of non-Hodgkin’s lymphomas: Summary and description of a working formulation for clinical usage. Cancer 49:2112-2135, 1982 53. Gold JE, Castella A: Polymorphic reticulosis: T- or B-cell malignancy. Laryngoscope 99:989-990, 1989 (letter) 54. Lin GZ, Shu GH, Lin S-H, et al: Polymorphic reticulosis: A malignant lymphoma of B-cell lineage. Laryngoscope 09:307-310. 1989 55. Fellbaum C, Hansmann M-L, Lennert K: Malignant lymphomas of the nasal cavity and paranasal sinuses. Virchows Arch A Pathol Anat Histopathol414:399-405, 1989

POLYMORPHIC

RETICULOSIS

56. Frierson HF, Jr, Innes DJ, Jr, Mills SE, et al: Immunophenotypic analysis of sinonasal non-Hodgkin’s lymphomas. HUM PATHOL. 20:63&642,1989 57. Frierson HF, Jr, Mills SE, Innes DJ, Jr: Non-Hodgkin’s lymphomas of the sinonasal region: Histologic subtypes and their clinicopathologic features. Am J Clin Path01 81:721-727, 1984 58. Ng CS, Chan JKC, Lo STH: Expression of natural killer cell markers in non-Hodgkin’s lymphomas. HUM PATHOLl&1257-1262,1987 59. Borisch B, Hennig 1, Laeng RH, et al: Association of the subtype 2 of the Epstein-Barr virus with T-cell non-Hodgkin’s lymphoma of the midline granuloma we. Blood 82:858-864, 1993 60. Peiper SC: Angiocentric lymphoproliferative disorders of the respiratoty system: Incrimination of Epstein-Barr virus in pathogenesis. Blood 82:687-690, 1993 61. Delsol G, Brousset P, Chittal S, et al: Correlation of the expression of Epstein-Barr virus latent membrane protein and in situ hybridization with biotinylated BumHI-W probes in Hodgkin’s disease. Am J Path01 140:247-253, 1992 62. Herbst H, Dallenbach F, Hummel M, et al: Epstein-Barr virus latent membrane protein expression in Hodgkin and_ReedSternberg cells. Proc Natl Acad Sci U S A 88:476&4770, 1991

465

(Strickler et al)

63. Hamilton-Dutoit SJ, Pallesen G: A survey of Epstein-Barr virus gene expression in sporadic non-Hodgkin’s lymphomas: Detection of Epstein-Barr virus in a subset of peripheral T-cell lymphomas. Am J Pathol 140:1315-1325, 1992 64. Jones JF, Shurin S, Abramowsky C, et al: T-cell lymphomas containing Epstein-Barr viral DNA in patients with chronic EpsteinBarr virus infections. N Engl J Med 318:733741, 1988 65. Katzenstein AA, Peiper SC: Detection ofEpstein-Barr virus genomes in lymphomatoid granulomatosis: Analysis of 29 cases by the polymerase chain reaction technique. Mod Pathol 3:435-441. 1990 66. Lee SH, Su I-J, Chen R-L, et al: A pathologic study of childhood lymphoma in Taiwan with special reference to peripheral T-cell lymphoma and the association with Epstein-Barr viral infection. Cancer 68:19541962, 1991 67. Richel DJ, Lepoutre JMM, Kapsenberg JG, et al: Epstein-Barr virus in a CD8positive T-cell lymphoma. Am J Pathol 136:109.%1099, 1990 68. Su 1-J. Lin K-H, Chen C-J, et al: Epstein-Barr virus-associated peripheral T-cell lymphoma of activated CD8 phenotype. Cancer 66:2557-2562, 1990