Age: 57.0
Sex: M
Vaccine: COVID19
Symptoms: Biopsy lymph gland, Biopsy skin, Blood immunoglobulin M, Blood test, Gene sequencing
Clinical narrative: Primary cutaneous marginal zone lymphoproliferative disorder (PCMZLPD); This literature-non-study case was reported in a literature article and describes the occurrence of LYMPHOPROLIFERATIVE DISORDER (Primary cutaneous marginal zone lymphoproliferative disorder (PCMZLPD)) in a 57-year-old male patient who received mRNA-1273 (Spikevax) for COVID-19 prophylaxis.   LITERATURE REFERENCE:     No Medical History information was reported.   In February 2021, the patient received first dose of mRNA-1273 (Spikevax) (unknown route) 1 dosage form. In March 2021, received second dose of mRNA-1273 (Spikevax) (unknown route) dosage was changed to 1 dosage form. In 2021, the patient experienced LYMPHOPROLIFERATIVE DISORDER (Primary cutaneous marginal zone lymphoproliferative disorder (PCMZLPD)) (seriousness criterion medically significant). At the time of the report, LYMPHOPROLIFERATIVE DISORDER (Primary cutaneous marginal zone lymphoproliferative disorder (PCMZLPD)) had resolved.      DIAGNOSTIC RESULTS (normal ranges are provided in parenthesis if available): In 2021, Biopsy lymph gland: showed no evidence of nodal involvement by LPD.. In 2021, Biopsy skin: revealed a diffuse dermal infiltrate of small to medium-sized lymphocytes with plasma cells and rare histiocytes. No polarizable foreign material or granulomatous inflammation was identified. The infiltrate was composed of nodular aggregates of CD20+ and CD79a+ B cells surrounded by CD3+ T cells. The neoplastic B cells colonized germinal center follicles as highlighted by CD21. The B lymphocytes reacted with BCL-2 and were negative for BCL-6, CD10, CD43, and cyclin D1. CD5 marked the T cells. PD-1 labeled scattered follicular helper T cells. The CD4:CD8 ratio was 56:1. Kappa light chain restriction was identified by in situ hybridization with a kappa: lambda ratio at 30:1. A diffuse and nodular dermal infiltrate of lymphocytes with histiocytes and plasma cells; at hematoxylin and eosin (H&E), 40x and H&E, 200x. and demonstrated a diffuse dermal infiltrate of lymphocytes, which  consisted of CD20+ and CD79a+ B cells with CD3+ T cells.. In 2021, Blood immunoglobulin M (35-242 mg/dl): 305 mg/dl elevated. In 2021, Blood test: revealed thrombocytopenia. In 2021, Gene sequencing: The result for IgH was polyclonal. For IgK, a monoclonal rearrangement was detected. and B-cell gene rearrangement studies of the lymph node did not show IgH or IgK clonality.. In 2021, Immunohistochemistry: No polarizable foreign material or granulomatous inflammation was identified. The infiltrate was composed of  nodular aggregates of CD20+ and CD79a+ B cells surrounded by CD3+ T cells. The neoplastic B cells colonized germinal center follicles as highlighted by CD21. The B lymphocytes reacted with BCL-2 and were negative for BCL-6, CD10, CD43, and cyclin D1. CD5 marked the T cells. PD-1 labeled scattered follicular helper T cells. The CD4:CD8 ratio was 5-6:1.. In 2021, Light chain analysis: Kappa light chain restriction was identified by in situ hybridization; kappa (200x) and lambda (200x). and No light chain restriction was identified by in situ hybridization.. In 2021, Physical examination: A red nodule of 1.1x0.9 cm was noted on left upper arm with an adjacent 2 mm red papule. A firm, erythematous nodule over the left upper arm at the site of vaccine inoculation and a smaller papule located laterally to the nodule.. In 2021, Positron emission tomogram: uncovered a few avid left axillary lymph nodes measuring up to 1.4 x 0.9 cm (standard uptake value [SUV] 4.0) and an intensely avid right inguinal lymph node measuring 1.3 x 1.2 cm (SUV 11.9). and showed resolution of the inguinal and axillary lymphadenopathy..     For mRNA-1273 (Spikevax) (Unknown), the reporter considered LYMPHOPROLIFERATIVE DISORDER (Primary cutaneous marginal zone lymphoproliferative disorder (PCMZLPD)) to be related.    No concomitant medications were reported.  A 57-year-old previously healthy man presented to dermatology clinic for a skin nodule on the left upper arm. He had received the Moderna (mRNA-1273) vaccine in Feb-2021 in the left upper arm and completed the second dose of the Moderna vaccination series in Mar-2021 in the same arm. The lesion appeared at the injection site a few weeks after the first dose and continued to progress in size after the second dose.  The patient underwent localized radiation therapy with excellent response. Upon 1-month follow-up after completing radiation, the lesions subsided with hyperpigmentation. Repeat PETCT showed resolution of the inguinal and axillary lymphadenopathy. There was no evidence of recurrence during a follow-up period of 8 months.  Reported a case of PCMZLPD at the inoculation site after the Moderna COVID-19 vaccine. While the development of PCMZLPD in this patient could be incidental and not related to COVID-19 vaccination, given the temporal and spatial relationship of the lesion to the COVID-19 vaccine inoculation, speculated that the development of PCMZLPD may be associated with COVID-19 vaccination.  No treatment medications were provided.  Company Comment: This is a literature-non-study case concerning a 57-year-old male patient, with no medical history reported, who experienced the unexpected serious (medically significant) event of LYMPHOPROLIFERATIVE DISORDER (reported as Primary cutaneous marginal zone lymphoproliferative disorder), a few weeks after the first dose of mRNA-1273 (Spikevax) and continued to progress in size after the second dose.  On exam, there was a 1.1   0.9 cm red nodule on his left upper arm with an adjacent 2 mm red papule. A skin biopsy specimen of the nodule revealed a diffuse dermal infiltrate of small to medium-sized lymphocytes with plasma cells and rare histiocytes. The CD4:CD8 ratio was 56:1. Kappa light chain restriction was identified. Gene rearrangement studies were conducted. The findings support the diagnosis of Primary cutaneous marginal zone lymphoproliferative disorder. Systemic workup revealed thrombocytopenia and an elevated IgM level at 305 mg/dL (normal range: 35242 mg/dL). No abnormal M spike was detected. Positron emission tomography computed tomography uncovered a few avid left axillary lymph nodes measuring up to 1.4 - 0.9 cm (standard uptake value [SUV] 4.0) and an intensely avid right inguinal lymph node measuring 1.3 - 1.2 cm (SUV 11.9). A biopsy of the right inguinal lymph node showed no evidence of nodal involvement by LPD. B-cell gene rearrangement studies of the lymph node did not show IgH or IgK clonality. The patient underwent localized radiation therapy with excellent response. Upon 1-month follow-up after completing radiation, the lesions subsided with hyperpigmentation. Repeat PETCT showed resolution of the inguinal and axillary lymphadenopathy. There was no evidence of recurrence during a follow-up period of 8 months. No further clinical information was available for medical review. The benefit-risk relationship of mRNA-1273 (Spikevax) vaccine is not affected by this report.