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Outcomes of primary thyroid non-Hodgkin's Lymphoma: a series of nine
consecutive cases. Med Oncol. 2007;24(2):203-8.
Primary
non-Hodgkin's lymphoma (NHL) of the thyroid gland is a rare disease
with an incidence of 0.5 per 100,000 population. Stages IE and IIE
thyroid NHL have been traditionally treated by surgical resection;
however, modern treatment consists of chemotherapy and local
radiotherapy, and surgery is often reserved for tissue diagnosis and
relief of airway compression. We retrospectively reviewed the
management and outcomes of nine consecutive patients with thyroid NHL,
eight females and one male (median age 63 yr, range 34-71 yr) treated
between 1994 and 1999. Five patients had disease stage IE and 4 stage
IIE. Median follow-up was 72 mo. Pathohistology and
immunohistochemistry identified two patients with mucosa-associated
lymphoid tissue (MALT), three follicular center cell lymphoma (FCC),
two patients large B-cell lymphoma (BLCL), one a marginal zone
lymphoma (MZL), and one patient a peripheral T-cell lymphoma (PTCL).
Total thyroidectomy was performed in three patients and subtotal
thyroidectomy in four. One (MALT) patient underwent surgery alone;
three patients surgery, radiotherapy, and chemotherapy (two FCC, one
PTCL); three patients surgery and chemotherapy (one MALT, one FCC, one
LBCL); and two chemotherapy alone (one LBCL, one MZL). Median survival
was 79 mo (range 13-124 mo). The PTCL patient, a 34-yr-old man, died
from disseminated disease at 13 mo despite secondary chemotherapy, and
one LBCL patient with extensively invasive local disease died from
stroke 17 mo after diagnosis. The remaining seven patients remain in
remission with no local or systemic relapse at a mean of 86 mo. With
appropriate therapy primary thyroid NHL has a favorable course;
however, prognosis depends on the histology, local spread, and the
stage of the disease at presentation, as well as the patient's
performance status. Surgery in combination with chemotherapy and/or
radiotherapy is still warranted for intermediate and high-grade
thyroid NHLs, with over 77% of patients achieving long-term remission.
Peripheral T-cell lymphoma carries a poor prognosis.
Primary thyroid
lymphomas.
Curr Treat Options Oncol. 2004 Aug;5(4):307-13.
Primary
thyroid lymphoma is a rare disease that continues to produce
diagnostic and therapeutic dilemmas. There was great difficulty in
distinguishing thyroid lymphoma from anaplastic thyroid carcinoma but,
because of new immunocytochemical staining techniques and increased
cytopathologic knowledge, our ability to diagnose thyroid lymphoma has
improved drastically over the past decade. Surgery that was once the
mainstay of treatment for this disease, now plays a minimal role.
Current treatment regimens for primary thyroid lymphoma consist of
chemotherapy (cyclophosphamide, doxorubicin, vincristine, and
prednisone) and external beam radiation. The overall and distant
relapse rates have been shown to be significantly lower in those
patients receiving combined modality therapy compared to chemotherapy
or radiation alone. Although the role of surgery has changed over
time, it continues to play an important role, especially in confirming
diagnoses through open biopsies, potentially providing local control
in the more indolent subtypes, and may play a role in the palliation
of symptoms for large obstructive lymphomas. The evolving
classification of extranodal lymphomas has brought about a better
understanding of the biologic behavior of these tumors. Most thyroid
lymphomas are B-cell origin, with six different histologic subtypes,
but there appears to be two distinct clinical and prognostic groupings
of these rare tumors. The more indolent lymphomas are the subgroup of
mucosa-associated lymphoid tissue (MALT) lymphomas comprising
approximately 6% to 27% of thyroid lymphomas. This subgroup, when
localized to the thyroid (stage IE), responds well to total
thyroidectomy or radiation with a complete response rate of more than
90%, leading some authors to recommend surgery as primary therapy in
the treatment of localized MALT lymphomas. Therefore, surgery as a
primary treatment for thyroid lymphomas would only be recommended
under ideal conditions, such as MALT subtype stage IE only, and
completely resectable with minimal morbidity. Unfortunately, this
scenario is rarely the case. The more common subtype, comprising up to
70% of cases, is diffuse large B-cell lymphoma. This subtype appears
to have the most aggressive clinical course with almost 60% of these
tumors diagnosed with disseminated disease. Up to 40% of all diffuse
large cell lymphomas appear to have undergone transformation from a
MALT lymphoma, but they behave in a similar fashion to diffuse large
cell lymphomas. Treatment for these tumors should include chemotherapy
and radiation. The overall 5-year survival for this aggressive group
is less then 50%. Surgery is rarely beneficial in diffuse large cell
lymphoma and the mixed large cell subtypes because the disease is
generally disseminated and surgical excision of all disease is not
possible or associated with increased morbidity. However, there may be
a role for palliative surgical debulking to alleviate obstructive
symptoms while the patient is undergoing standard chemotherapy and
radiation.
Outcome analysis for
stage IE and IIE thyroid lymphoma.
Am J Clin Oncol. 2004 Apr;27(2): 178-84.
Previous reports have revealed modest results in the management of
thyroid lymphoma with radiotherapy alone. This retrospective report
evaluates the outcome of patients treated for thyroid lymphoma with
radiotherapy alone and with combined modality therapy (chemotherapy
and radiotherapy) at a single institution. Twenty-seven patients with
stages IE and IIE non-Hodgkin's lymphoma of the thyroid gland were
treated between 1960 and 1998 at Barnes-Jewish Hospital, of which 14
patients were stage IE and 13 patients were stage IIE. The median age
at diagnosis was 67 years, and there were 21 females and 6 males
evaluated. The median follow-up time was 38 months (range: 3-279
months). All patients had histologically proven non-Hodgkin's
lymphoma, of which 22 patients (81%) were intermediate grade.
Treatment consisted of radiotherapy alone in 19 patients and a
combined modality therapy in 8 patients. The median radiation dose to
the thyroid bed was 44 Gy, and most patients received a
doxorubicin-containing regimen administered prior to radiotherapy.
Patient, tumor, and treatment-related characteristics were evaluated
using Cox regression analysis. Local-regional tumor control,
disease-free survival (DFS), and overall survival (OS) were calculated
using the Kaplan-Meier method. Four patients had local relapse in this
series, with a crude local tumor control rate of 85%. No factor was
determined to be significant for local tumor control. The actuarial
5-year DFS and OS for the entire cohort were 57%, and 56%,
respectively. In terms of DFS, both age and stage were statistically
significant. The 5-year actuarial DFS for patients less than age 65
years was 83% versus 37% for those more than this age (p = 0.024).
Furthermore, the 5-year actuarial DFS for patients with stage I and II
disease was 69% and 45%, respectively (p = 0.022). In multivariate
analysis, age continued to be significant for DFS (p = 0.049). Overall
survival analysis revealed age, local tumor control, and stage to be
significant in univariate analysis. Multivariate analysis was further
carried out using Cox proportional hazard model, and it revealed age
(p = 0.006) and local tumor control (p = 0.007) to be significant.
Primary thyroid gland lymphomas have a favorable outcome with
appropriate therapy, but prognosis depends on both clinical stage and
age at presentation. Because of the risk of both local-regional and
distant failure, combined modality approaches that use chemotherapy
with radiotherapy are warranted for intermediate- and high grade
thyroid lymphoma.
Clinical
presentation and treatment of non-Hodgkin's lymphoma of the thyroid
gland. Ann
Surg Oncol. 2001 May;8(4):338-41.
BACKGROUND:
Non-Hodgkin's lymphoma (NHL) of the thyroid is a rare malignancy. The
traditional approach to curative treatment of localized (stages I and
II) NHL of the thyroid gland is surgical resection. The recent success
of multimodality chemoradiotherapy suggests that surgery should be
reserved for providing a tissue diagnosis or relief from acute airway
obstruction. It is questionable whether this has made an impact on
treatment approaches. METHODS: Retrospective chart review was
conducted for all cases of localized NHL of the thyroid gland treated
at Roswell Park Cancer Institute between January 1970 and January
1999. RESULTS: Ten patients (8 women, 2 men) with a mean age of 56.8
years were identified. Nine patients (90%) presented with a neck mass;
seven patients (70%) had a history of Hashimoto's disease. Nine
patients (90%) had extensive investigations to rule out extrathyroidal
disease. All patients were treated with either a total thyroidectomy
(eight patients) or a thyroid lobectomy (two patients). Nine (90%)
were initially treated outside of Roswell Park Cancer Institute and
referred secondarily for consideration of further therapy. Adjuvant
therapy consisting of cyclophosphamide-based chemoradiotherapy was
administered to nine patients. Overall survival was 80% at a mean
follow-up of 8.6 years with a disease-specific survival rate of 100%.
CONCLUSIONS: A review of the literature suggests that fine needle
aspiration (FNA) with flow cytometry and immunohistochemistry can be
used to accurately diagnose NHL of the thyroid gland. Open biopsy
should be reserved for cases where this technique is not available or
where the diagnosis can not be confirmed by FNA alone. Extrathyroidal
NHL should be ruled out by chest x-ray, CT scan of the abdomen, and
bone marrow biopsy. Further review suggests that the most efficacious
therapy is systemic chemotherapy in combination with radiation for
local control. Debulking surgery should be used only to provide relief
from acute airway obstruction.
Primary thyroid
lymphoma: a retrospective analysis of prognostic factors and treatment
outcome for localized intermediate and high grade lymphoma. Am J Clin
Oncol. 2001 Jun;24(3):299-305.
Non-Hodgkin's
lymphoma presenting in the thyroid gland is uncommon. A review of the
King Faisal Specialist Hospital and Research Centre (KFSH & RC)
experience was performed to assess treatment outcome and prognostic
factors in this rare extranodal presentation of localized lymphoma.
Sixty patients treated at KFSH & RC between 1975 and 1995 were
identified, and their records were reviewed retrospectively. Eight
patients who had stage III or IV disease, low grade, or did not
complete their prescribed treatment were excluded from the study.
There were 38 female and 14 male patients with a median age of 59.5
years at the time of diagnosis (range: 10-87 years). Thirty-five of
the 52 patients underwent diagnostic partial or total thyroidectomy at
other institutions based on a preoperative assumption of thyroid
carcinoma. All 52 patients had non-Hodgkin's lymphoma of intermediate
(94%) or high (6%) grade. Detailed staging was carried out in all
patients; 16 patients (31%) had disease confined to the thyroid gland
(stage IE), whereas 36 (69%) had associated disease in cervical lymph
nodes and/or the mediastinum (stage IIE) disease. All patients were
treated with curative intent. A total of 18 patients (35%) were
treated with a single-modality treatment--radiotherapy alone in 2,
chemotherapy alone in 13, and surgery alone in the remaining 3
patients. The majority of patients (34/52; 65%) were treated with a
combined-modality approach. The overall relapse-free survival (RFS)
and overall survival (OS) at 5 years were 72% and 88%, respectively.
There were no significant differences in outcome between those treated
with single-modality and those with combined-modality therapy. A
univariate analysis showed that the presence of mediastinal lymph node
involvement was the most important prognostic factor affecting both
RFS and OS. Patients with Hashimoto thyroiditis and without "B"
symptoms were found to have a significantly higher RFS without
influence on the OS. However, patients who had a good performance
status (PS) of 0, 1, and 2 were found to have a significantly higher
overall survival in comparison to those with poor performance status.
Age, sex, stage, histology, lactic acid dehydrogenase level, tumor
bulk, and the treatment modality were not found to correlate with RFS
or OS. Mediastinal involvement and PS were found to be the most
important independent prognostic factors influencing RFS and OS.
Non-Hodgkin's
lymphoma of the thyroid: a retrospective review of all patients
diagnosed in Nottinghamshire from 1973 to 1992. Clin Oncol (R Coll
Radiol). 1996;8(6):371-5.
The
pathological and clinical features were reviewed of all primary
non-Hodgkin's lymphomas (NHL) of the thyroid gland diagnosed between
1973 and 1992 in the population (1.1 million) served by the Nottingham
and North Nottinghamshire Health Authorities. Of the 43 patients with
histologically proven NHL, three had low grade mucosa associated
lymphoid tissue (MALT) lymphomas (Stage IEA, 2; Stage IIEA, 1), 35 had
intermediate or high grade lymphomas, Stage IEA or IIEA (intermediate
MALT, 2; high grade MALT, 14; B-cell diffuse centroblastic, 17;
anaplastic large cell (Ki-1) of null cell type, 1; high grade
unclassifiable, 1), and one had unclassifiable NHL Stage IIEA. One
patient had Stage IIIEA disease (high grade MALT) and three had stage
IVA disease (high grade MALT, 2; B-cell diffuse centroblastic, 1). The
median age was 68 years (range 45-86) with a female: male ratio of
6:1. For the 35 patients with intermediate or high grade thyroid NHL
(Stages IEA and IIEA) the 5- and 10-year cause specific survival was
60%. The 21 patients treated between 1985 and 1992 initially with
chemotherapy (except stage IEA (< 5 cm diameter) had a 5-year cause
specific survival of 69% (95% CI 48-90) compared with 46% (95% CI
19-73) for the 14 patients treated between 1973 and 1984 with initial
radiotherapy (Chi 2 = 1.62). The survival of those patients with
intermediate or high grade MALT lymphomas was not significantly
greater than of those patients with B-cell diffuse centroblastic NHL.
Primary thyroid
lymphoma: clinical features, treatment and outcome: a report of 8
cases. N Z Med J. 1994 Aug 10;107(983):301-4.
AIM. To assess
the clinical findings and response to treatment of patients with
primary thyroid lymphoma. METHODS. Patients with primary thyroid
lymphoma were identified by reviewing the diagnoses of all patients
with thyroid malignancies diagnosed at Christchurch Hospital between
1980-91. The records of patients with primary thyroid lymphoma were
abstracted. RESULTS. During the 12 year period eight patients (6
females, 2 males) with primary thyroid lymphoma were diagnosed and
treated. The median age was 78 years (range 18-90 yr). All patients
presented with recent thyroid masses and obstructive symptoms were
prominent. Two patients were initially referred with endocrine
dysfunction--one thyrotoxic and one hypothyroid. Six patients had
nonHodgkin lymphoma and two Hodgkin's disease, with all having stage
IA disease. Two patients were treated by thyroidectomy, and in the
remaining six patients the thyroid lymphoma masses regressed following
radiotherapy with the two youngest patients also receiving
chemotherapy. At follow up all five elderly patients have since
died--two of disseminated lymphoma, two of concurrent cancers and one
of vascular disease, and the three younger patients remain in
remission after 4.5, 6.5 and 10.5 years. CONCLUSION. Primary thyroid
lymphoma usually presents with obstructive symptoms, but there may be
associated thyroid dysfunction. Thyroid lymphoma masses respond well
to radiotherapy.
Malignant lymphoma
of the thyroid gland: a clinicopathologic study of 108 cases.
Am J Surg Pathol.2000 May;24(5):623-39.
We report a
retrospective clinicopathologic study of 108 primary thyroid gland
lymphomas (PTLs), classified using the REAL and proposed WHO
classification schemes. The patients included 79 women and 29 men,
with an average age of 64.3 years. All patients presented with a
thyroid mass. The PTLs were classified as marginal zone B-cell
lymphoma of mucosa-associated lymphoid tissue (MALT) or MZBL (n = 30),
diffuse large B-cell lymphoma (DLBCL) with MZBL (n = 36), DLBCL
without MZBL (n = 41), and follicle center lymphoma (FCL; n = 1).
Excluding the FCL, features of lymphomas of MALT-type were identified
in all groups, despite a follicular architecture in 23% of cases.
Lymphocytic thyroiditis (LT) was identified in 94%. Ninety-one percent
of patients presented with stage IE or IIE disease, whereas 69% had
perithyroidal soft tissue infiltration. All patients were treated with
surgical excision followed by adjuvant therapy (76%): chemotherapy
(15%), radiation (19%), or a combination of radiation and chemotherapy
(42%). Disease-specific survival was 82% at last follow up (mean, 82.8
mos) and 79% at 5 years. Statistically, stages greater than IE,
presence of DLBCL, rapid clinical growth, abundant apoptosis, presence
of vascular invasion, high mitotic rate, and infiltration of the
perithyroidal soft tissue were significantly associated with death
with disease. No patients with MZBL or stage IE disease died with
disease. In summary, PTLs typically occur in middle- to older-aged
individuals as a thyroid mass, with a predilection for females.
Despite their histologic heterogeneity and frequent simulation of
other lymphoma subtypes, virtually all PTLs are lymphomas of MALT-type
arising in the setting of LT. Mixed DLBCL and MZBL are common.
Overall, PTLs have a favorable outcome with appropriate therapy, but
prognosis depends on both clinical stage and histology. MZBL and stage
IE tumors have an excellent prognosis, whereas tumors with a large
cell component or DLBCL or stage greater than IE have the greatest
potential for a poor outcome.
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