A 43-year-old Chinese female inadvertently found multiple breast masses in April 2018, the larger one was about 2cm*3cm, self-conscious hard, clear border, good mobility, tenderness, no fever, itching, redness, etc. On June 6, 2018, she visited Chongqing Cancer Hospital & Chongqing University Cancer Hospital and a puncture biopsy of a right breast mass was performed. On June 21, the tissue examination revealed peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), and immunohistochemistry showed CD45 + Bcl-6 scattered + Bcl-2 scattered + CD5 + MUM-1 individual + Cyclin D1 + CD99dim + Fli-1 + Ki67 + > 80%, CD13- CD15- CD33- CD68(kp1)- CD68(PG-M1)- CD117- CD56- MPO- TdT- CK- Syn- CgA- Desmin- Myogenin- MyoD1- CK7- CD3- CD20- CD21- CD10- CD23- EBER- positive control + NSE-. On June 27th 18-F-fluorodeoxyglucose (FDG) positron emission tomography (PET) revealed that an abnormal FDG accumulation in bilateral neck, clavicular region, axillary fossa, upper limb, mediastinum, double hilar, abdominal wall, retroperitoneum, intestinal space, pelvic cavity, bilateral inguinal multiple lymphadenopathy, double lung, bilateral breast, stomach wall, left adrenal gland, spleen, occipital, under the chest wall multiple masses, and the whole body bone with high metabolic activity (SUVmax: 4.75–23.4), considering lymphoma involvement. On June 29, the first course of chemotherapy was started with P-CHOP (Pegaspargase 3750iu, epirubicin 80mg, cyclophosphamide 1.2g, vindesine 4mg, prednisone 500mg) and intrathecal injection, which cerebrospinal fluid was normal. On July 16th, the second course of HD-MTX(5g)and intrathecal injection were given. After a few days the masses reduced in size. On August 8th, the third course of treatment was given to P-CHOP and intrathecal injection. On August 23, the fourth course of HD-MTX༈5g༉ was given and intrathecal injection. However, in the chemotherapy period, the masses increased again, and the disease progression (PD) was evaluated.
On September 5, 2018, the left breast mass biopsy was performed again and the pathological presentation showed thar left breast mass conformed to peripheral T cell lymphoma with T-follicular helper cell phenotype, and immunohistochemistry were CD3 + CD20- CD21- ki-67 + 80% Bcl-2 + CD2p + CD5 + CD7 + CD4 + CD8 + CD56- GranzymB focal area + TIA-1 focal area + Perforin- TdT- PD-1 + CXCL-13- CD10- Bcl-6 + CD30- MUM- 1 scattered in + Cyclin D1 + 10% SOX11- CD23- CD117- CD33- CK- LCA+; Simultaneously, gastroscopy and biopsy showing pathological findings that stomach body conformed to peripheral T-cell lymphoma, NOS, and immunohistochemistry showed tumor cells CD3 + + CD20- CD21- Bcl-2 + Ki-67 (about 30%+) CD10- Bcl − 6 + MUM-1 (scattered in small amount+) CD5 + + CD23- CyclinD1 (scattered in small amount+) SOX11 (small stove+) CD30- c-myc (about 70%) TdT- PAX-5- p53 (about 20%) CD43++ κ chain (small stove+) λ chain- CD4 + + CD8 + + CD56- CD2 + CD7p+, EBER in situ hybridization-. On September 8 and October 1, respectively, the 5th and 6th courses of the GDP regimen (gemcitabine 1.65g*2d, cisplatin 120mg*2d, and dexamethasone 40mg*4d) were combined with histone deacetylase inhibitors - Chidamide. On October 30, the assessment again considered the progress of the disease (PD).
She admitted our hospital on November 7, 2018. Specialist examination: chronic illness, anemia, obvious pigmentation of the whole body, a large amount of scattered dandruff, superficial lymph nodes (submandibular, neck, armpit, trochle, groin, armpit) reaching the enlarged lymph nodes, which the texture is tough, fixed, obvious pain of inguinal lymph nodes. Both hearing weaked, the double breast touched multiple masses, with no tenderness, toughness, clear borders, good mobility, and mild edema in both lower limbs. Bone marrow cytology showed that bone marrow hyperplasia was active and lymphocyte morphology was abnormal, considering Non-Hodgkin's lymphoma bone marrow image and iron deficiency anemia (NHL-BMI, IDA). Skin biopsy pathology showed that pre-neck V-zone skin consistent with peripheral T-cell lymphoma, tumor cell CD20- CD2 + CD3 + CD4 + CD5 + CD7 + CD8 + CD30- GranB- Ki-67 approximately 10% TCR recombinant+. As a result, combined with the patient history and examination, the diagnosis of refractory PTCL was established. So on November 9th and December 3rd, two courses of DEAD (doxorubicin liposome 20mg*3d, etoposide 150mg*3d, cytarabine 500mg*3d, dexamethasone 15mg*5d) were combined with Chidamide, which consciously the masses shrinked after chemotherapy, but the interval increased again. On December 18, the CLAG program (Cladribine 10 mg*5d, cytarabine 1g*4d, G-CSF 150ug*3d) was combined with thalidomide, and Simultaneously, the second generation gene sequencing showed: Notch1 and SOCS1 mutations.
At the beginning of January 2019, the patient's skin lesions, facial and limb edema were aggravated, and the finger joints were seen in the masses (Fig. 1), which the disease progression (PD) was evaluated. On January 14th, the PD regimen (bortezomib 2.27mg d1, 4, 8, 11 and dexamethasone 20mg d1-4, 8–11) was given, and edema slightly relieved on the 2nd day of treatment. But on January 18th, the whole body began ro appear a large number of scattered masses, with highlighting the leather surface, hard, no tenderness, and progressively enlarging, which the largest one is located in the lower abdomen, about 3cm*5cm (Fig. 2), and the whole body appeared edema again. Therefore, we added bcl-2 inhibitors - venetoclax, and the disease still progressed after the end of the treatment.
On January 29th we tried PD-1 antibody - Carellidizumab (SHR-1210, 200mg, every 3 weeks) (Suzhou Shengdia Biomedical Co., Ltd.) combined with decitabine (25mg*5d). After treatment, the body masses was significantly reduced (Fig. 3), some of the masses disappeared, edema subsided, and evaluation of partial remission (PR). Unfortunately, before receiving the second cycle, the patient developed IV° myelosuppression and severe pulmonary infection. Despite the step up of antibiotic therapy and the addition of corticosteroids, the patient worsened, and eventually died of respiratory failure (Table 1).
Table 1
|
Start time
|
therapy
|
Number of cycles
|
effect
|
1st
|
2018/6/29,
2018/7/16,
2018/8/8,
2018/8/23
|
P-CHOP (Pegaspargase, Epirubicin, Cyclophosphamide, Vindesine, Prednisone)
HD-MTX
P-CHOP
HD-MTX
|
4
|
Stable disease;
Progressive disease
|
2nd
|
2018/9/8,
2018/10/1
|
GDP (Gemcitabine, Cisplatin, Dexamethasone) + Chidamide(20mg, po, twice a week)
|
2
|
Progressive disease
|
3rd
|
2018/11/9,
2018/12/3
|
DEAD (Doxorubicin liposome, Etoposide, Cytarabine, Dexamethasone ) + Chidamide(20mg, po., twice a week)
|
2
|
Progressive disease
|
4th
|
2018/12/18
|
CLAG (Cladribine, Cytarabine ) + Thalidomide(25mg, po., daily)
|
1
|
Progressive disease
|
5th
|
2019/1/14
|
PD (Bortezomib, Dexamethasone) + Venetoclax
|
1
|
Progressive disease
|
6th
|
2019/1/29
|
Carellidizumab (200mg iv. every 3 weeks) + Decitabine (25mg iv. d2-6)
|
1
|
Partial response
|