Lymphomas in Rio: International Tutorial Pathology

Patient: F.B. S., 77 years-old , male
3 months ago started with paresthesias in feet and feeling heavy in the legs. Lost 15 kg in this period. The patient reports still tiredness. No sweating and fever.
Pathological background: active smoking (pipe) since 26 years. Patient with systemic arterial hypertension, atrial fibrillation, type 2 diabetes mellitus.
Increased cervical , supraclavicular and bilateral inguinal lymph nodes

July:- Hb 16,2, VCM 85,9, leuco 12310 (9491n/ 1059ly/419 eo), plats 193.000, Cr 0,76, Ur 35
*August: – Hb: 15,7, VCM: 88,2, leuco: 6520 (456b/3912s/326e/978 ly/848 mono), plats: 115.000, Retículo: 122.570, FAN: NR, FR: NR, VHS: 30mm, PCR: 19,6, Ur: 36, Creat: 0,77, EFP no monoclonal, IGG: 1220, IGA: 364, IGM: 323 (até 230), IGE: 527,0 U/L ( 0,0 – 140,0), C3: 134, C4: 31

Slide: Case 1 (Area C)

A 72 year old woman has had droopy left eye lid, difficult for opening her left eye and a feeling of a mass next to her eye for the past two months. She also has had a red eye for the same period.
She denied pain, photophobia, decreased visual acuity or diplopia.
She denies fevers, chills, myalgia, arthralgia, weight loss or night sweats.
No history of ocular trauma, surgery or any other ocular pathology
Past medical history
High blood pressure and type 2 diabetes mellitus.

Snellen: right eye 20/70 left eye 20/200
She had meibomitis and blepharitis of the right eye and a ptosis with conjunctival hyperemia of the left eye, with a vegetating mass located on the superior tarsus.

A MRN was performed. There was a expansive lesion, with well defined contours, with intermediate signal in t1 and hypersignal in t2, measuring 2,5x1x2,3 cm, anterior and lateral to the left eye globe, on the topography of the correspondent lacrimal gland, extending through the superior tarsus.
After injection of contrast, it was observed an intense and homogenous highlight of the lesion. The lesions has restriction to the diffusion of water (score of 715).

Eye-lid surgery was performed, and the resected lesion was sent to the Pathology department of UFF.
We received an irregular segment of tissue measuring 3,2×2,8×1,0 cm, pale and brownish.
There was a proliferation of round cells, with scant cytoplasm and hyperchromatic nuclei, compatible with Lymphoma. Then we performed immunohistochemical testing.

Slide: Case 2

male, 18 y-o, student.

2015, July
Complaint: cervical pain with sudden neck enlargement, most prominent at left side (17 days). No fever, no weight loss, no sweats, no pruritus.
Physical examination and USG: confluent lymph node enlargement at cervical left side.
Lab: discrete blood leukocytosis (WBC= 11,060), normal biochemistry, IgG+ CMV, IgG+ EBV and IgG+ Hepatitis A.
Biopsy after 2 weeks (cervical enlargement growing).

2016, March
Progressive growing skin lesion after local trauma. USG – heterogeneous subcutaneous lesion on right arm, measuring 1,9×1,5×0,8cm and 0,2cm below skin. Done skin biopsy.
PET-CT re-staging: extra nodal disease (skin and left lung).

2017, March
Pyloric stenosis syndrome, endoscopic biopsy done. Liver and kidney insufficiency.
Treatment prescribed (4th line): 4 IGEV, completed by April, 2017.
PET-CT re-staging: complete remission.

2017, May
Acute abdomen due to small intestine perforation treated by ileostomy. Evolved with abdominal abscess and dehiscence of suture; found enlarged mesenteric lymph nodes.
Death after 22 months of disease.

Slide: Case 3

73 year old Woman.
Left thigh tumor with clinical hypothesis of sarcoma.
Image exams not available.
She died after 3 months of the biopsy.

Slide: Case 4 (Area A)

Male, 43-years old
In February of 2014, the patient noticed a tumor in the left cervical region, and underwent a biopsy with diagnosis of Nodular Lymphocyte Predominance Hodgkin Lymphoma. PET-CT showed involvement of lymph nodes, L4 vertebra and femur; without infiltration of bone marrow.
ABVD protocol was initiated in October 2014, and eight cycles were conducted (until 09/2016) with partial response. After termination of QT, patient presented with idiopathic thrombocytopenic purpura treated with corticoid pulse therapy (05/2017).
Follow-up examination (PET-CT) in May 2018 showed progression of the disease with involvement of supra and infradiaphragmatic lymph nodes and spleen. A cervical lymph node biopsy was performed.

Slide: Case 5 (Area A) (Area E)

JLN, a 65-year-old man, natural and living in Nova Friburgo (RJ), working in sanitary surveil-lance.
He presentes for the past 2 and a half months with inappetence, anorexia and intermittent fever, reaching 102 oF, sometimes with chills. He also noticed a 30-lb weight loss in this time period.
At physical examination, he looked anemic, without palpable adenomegaly, and hepato-splenomegaly was found (spleen was palpable till umbilical scar).
Blood samples showed haemoglobin – 11,0, trombocytopenia (Platelets – 80.000), normal leukocytes count, as well as renal function and LDH. SGOT, SGPT and serum bilirubines were within normal range, but GGT and alkaline phosphatase levels were increased.
He was admitted for investigation of unknown origin fever and blood samples for HIV, viral hepatites and thick drop test were negative.
CT revealed retroperitoneal and hepatic hilum adenomegaly.
Bone marrow aspiration and biopsy were considered inconclusive.
After that, liver and hilum linfonodes biopsies were performed.
Three days after the liver biopsy, patient progressed with jaundice, direct bilirubin increase, altered state of consciousness, decrease of renal function, severe worsening of anemia and trombocytopenia.
Ultrasound examination was performed and two nodules were detected, suspicious for abscess. Tazocin and teicoplanin were begun, but briefly changed for ceftriaxone (negative blood cultures and trombocytopenia-risc related to Tazocin).
Patient presented progressive clinical and laboratorious improvement but evolved with subit reduced mental awareness, worsening of jaundice and renal function.
The brandnew diagnose of Hodgkin’s Lymphoma in hepatic hilum linfonode, with invasion of periportal space raised the questioning lymphomatous infiltration X infection, and chemoterapy using cyclophosphamide and corticosteroid was begun.
The patient evolved to refractory shock and death.

Slide: (Case 6)

A 6-year old girl, with confluent cervical lymphadenopathy (4.0 cm), since January 2018. There were any other symptoms.

Slide: (Area C)

R. V, male, 24 years old; priest
Patient noticed a left cervical lump in november of 2017 that was growing relatively fast. In February 2018 he went to a doctor that made a biopsy of the lymph node (this material sent to you).
Patient did not report B symptoms.
Pet CT in March 2018: Captation in a Left cervical lymph node levels II a and B mesuring 10,2×8,5 cm with SUV of 4,2 and late of 5,3.
HIV, HBV and HCV serologies negative. Hb 15,3, Leucocytes: 5090, Neutrophils: 2418, Lymphocytes: 2194, Monocytes: 351, Platelets: 172.000, Erythrocyte sedimentation rate: 3, Myelogram, bone marrow immunophenotyping and karyotype: normal.

Slide: Case 8 (Area A)

Female patient, 24 years old.
Multiple masses on soft tissue, skin, breasts, intra abdominal, maxillary sinus and mediasti-num.
Bone marrow aspiration negative for neoplasia.
Right thigh mass biopsy.
Gross: 3,2 x 2,2 x 1,6 cm fragment.

Slide: Case 9 (Área D)

A 50-year-old male presented in February 2011 because of night sweets and cervical/ axillar lymph nodes. Biopsy revealed classical HL (CD30+, CD15+, EBV negative) and bone marrow was also positive, characterizing stage IV disease. He was treated with 6 cycles of ABVD and achieved complete remission (CR).
For two years he remained asymptomatic, and in April, 2013 he started to feel back pain and leg swelling. CT re-evaluation demonstrated an L3 vertebral lesion. A biopsy was performed and was classified as relapsed classical HL, with the same histologic features described above. Given these findings, salvage chemotherapy was initiated (IGEV), followed by autologous stem cell transplantation (ASCT) and the patient achieved a second CR.
In August, 2017, a new enlargement of inguinal lymph node, associated with fever and night sweats, was observed. PET-CT showed multiple abdominal lymph nodes and bone lesions. Inguinal lymph node biopsy unexpectedly revealed ALK negative ALCL (CD2+, CD3+, CD5+, CD7-, CD4+, CD8-, CD20-, CD15-, CD30+, EBV-, CD10-, BCL6-, PD1-, PAX5-, TDT-). Patient was initiated on Brentuximab, maintained until now in partial remission, and was not considered eligible to a second ASCT.

Slide: Case 10 (Area A) (Area E)

Female, 44 years old.

Patient reports progressive loss of muscle strength in left lower limb associated with low back pain, fever and weight loss in the last 3 months.
Systemic sclerosis diagnosed 7 years ago previously treated with corticosteroids, and azathioprine for the last 4 years.

Pallor and loss of muscle strength in the lower limb. No palpable lymph nodes or organomegaly.

Infiltrative lesion involving 3rd lumbar vertebra and paravertebral soft tissue.
Surgical biopsy was performed addressing the bone and soft tissue.

Slide: Case 11 (Area E)

59-year-old male, HTLV1 carrier, first identified 20 years, and HBV infected, with cervical and axilary bilateral lymphandenopathy. He did not present B symptoms, the physical examination was otherwise unremarkable. His blood count and blood smear were normal and the bone marrow biopsy, negative.

Slide: Case 12 (Area B)

The patient is 36 years-old male, with personal antecedent of systemic arterial hypertension. He entered the hospital with a history of one year with edema and ulcerated lesions on the left upper limb of progressive growth. Previously, he looked for several medical services, and made four local biopsies, which results only in necrotic material. No B symptoms, lymphadenopathy or hepatosplenomegaly.

Slide: Case 13 (Area A)

“This is a 74 year old female patient with a previous history of gastric adenocarcinoma staging pT1 N0, treated with chemotherapy and gastrectomy, one year ago . Currently presenting with abdominal pain, weight loss, and the presence of multiple retroperitoneal, inguinal, mediastinal, and cervical lymph node enlargement, accompanied by hepatosplenomegaly, pulmonary nodules at chest CT / total abdomen. The histopathological findings were of atypical lymph node proliferation, necessary complementation with immunohistochemistry. NHL? Recurrence of stomach cancer?”

Slide: Case 14 (Area A)

A 69-year-old man, a retired engineer. He had undergone a radical prostatectomy with bilateral lymphadenectomy 7 years ago for Usual Acinar Adenocarcinoma of the Prostate (Gleason 3+3=6) at the AC Camargo Hospital. The surgery went normally, the resection margins and lymph nodes being free of neoplasia. The patient had no complementary treatment (radiotherapy and/or hormonal block).
In July, 2018, the patient presented himself at the BP-Beneficiência Portuguesa-as he had perceived the appearance of bilateral nodules in the inguinal region, but denying fever, weight loss or night sweats. He underwent ultrasound and tomography exams, which showed lymphadenopathies in the bilateral inguinal regions and in the left external iliac chain, measuring up to 2.5 x 1.3 cm in the latter. The imaging exam suggested the presence of neoplastic disease. These lymphadenopathies had not been evident in the prior exam, performed in 2014. The patient also referred to gastroesophageal reflux and urinary incontinence symptoms (sequelae of prostate surgery). He denied being a smoker and informed occasional consumption of alcoholic beverages (1-2 cans of beer per month). He also informed of his regular physical activity (physical conditioning and multifunctional gymnastics). A lymph node biopsy was made with a needle, but the anatomopathological exam was inconclusive, favoring reactional lymphoid hyperplasia, however with the recommendation to excise the lymph node for better appraisal. The excision of the lymph node was performed on August 14, 2018 (and the biopsy brought for discussion).

Slide: Case 15 (Area A)

Epigastralgia and retrosternal pain for 8 months. Gastric biopsy.

Slide: Case 16 (Area D)

Male patient, 34 yrs old, presenting with enlarged left tonsil and bulging of the palate, refractory to antibiotics.

Slide: Case 17 (Area A)

Clinical History
The patient is a 10-year-old girl with clinical history of significant dyspnea for 1 year, currently on home oxygen therapy and under investigation for pulmonary nodules. Physical exam shows: regular state, dyspneic, malnutrition.

Multiple nodules, bilaterally, tree-in-bud pattern associated with ground glass opacities.
Patient underwent wedge resection of right lung and the specimen was sent for pathological examination.

Past medical history
The patient had multiple visits to the emergency room due to pulmonary infections, with 4 hospital admissions for long periods, including stay in the intensive care unit.
She was diagnosed with multiple diseases: tuberculosis (she had close household contacts with tuberculosis; treated with RIPE), cystic fibrosis with pulmonary manifestations and COPD.
HIV test: negative
The patient was treat after biopsy result with 6 cycles of R-CHOP chemotherapy (finished 9 months ago)
Currently (October, 2018) on remission without supplemental oxygen
She is under investigation for immunodeficiency due to history of multiple pulmonary infections. Most recent laboratory results showed IgA and IgG levels way below the reference values.
IgA= 5mg/dL (nl=70-400mg/dL) e IgG= 270 mg/dL (nl=700-1.600mg/dL)

Slide: Case 18 (Area A)

A 47-year-old male was transferred to the Hospital de Clínicas de Porto Alegre (HCPA) from an emergency hospital due to lower back and lower limbs pain and progressive loss of strength in the lower limbs culminating in paraplegia. His symptoms had started three months earlier as only pain in the legs and in the lower back, which was attributed to “muscle pain” by the patient, who refused to look for help. Two months after the onset of the symptoms, he started to rapidly lose strength in the legs, and sought for canes to ambulate. One month later, he noticed a loss of 5 kilograms of weight, night sweats, and could not walk anymore, changing to a wheelchair without medical prescription. He was submitted to laboratory tests and a spine magnetic resonance imaging (MRI): the exams showed thrombocytopenia, hypoalbuminemia, increased serum creatinine and urea, increased thyroid-stimulating hormone (TSH), and low complement, and so empirical antibacterial treatment with piperacillin plus tazobactam was started. The spine MRI showed only disc protrusions and partial compression of the dura in L2, L3, L4, L5, and S1, to which the lumbar and leg pain were attributed. The patient was then referred to the HCPA for further investigation.

At admission, no pulmonary or cardiac alterations were found in the physical exam; the patient was oedematous in the lower limbs and in the scrotum; strength in the upper limbs was normal but was only grade 2 in the lower limbs; sensibility to touch, pain, and vibration was normal in all the four limbs. The cutaneous-plantar reflex was absent bilaterally. An arterial gas analysis was normal but for the increased lactate (3.1 mg/dL), and the hypothesis of sepsis due to urinary tract infection was made, so intravenous meropenem was started.

In the next day (D1), the patient presented tachycardia and dyspnoea, and, after 1.5 litre of Ringer lactate solution was infused with no alteration in the clinical parameters, he was transferred to the ICU. By this time, he was having auditory and visual hallucinations, and new blood exams were: lactate 3.1 mg/dL, sodium 131 mg/dL, urea 70 mg/dL, creatinine 1.72 mg/dL, aspartate-transaminase (AST) 62 IU/dL, and gamma-glutamyltransferase (?GT) 295 IU/dL. Norepinephrine infusion was started; a bedside thorax ultrasound showed an image compatible with atelectasis or consolidation in the left lung, and an abdominal computed tomography (CT) showed a 2.0 x 1.9cm mass in the right adrenal gland.

In the D3, blood tests showed platelets of 40,000/mm³, and a lumbar puncture showed increased protein (171mg/mL), normal glucose (35mg/mL), and increased leukocytes (19 cells/mm³, 92% lymphocytes), but was negative for Cryptococcus sp., other fungi, and acid-fast bacilli.

In the D5, a thorax CT showed left pleural effusion of approximately 500mL, and a thoracentesis was performed, with bright yellow transudate negative for both acid-fast bacilli and Epstein-Barr virus (EBV).

In the D6, an electroneuromyography (ENMG) diagnosed symmetrical severe sensitive and motor axonal polyneuropathy, predominating in distal motor axons. In the same day, the patient had a bowel movement for the first time since hospitalization, even with the use of laxatives and enema. Meropenem was suspended due to clinical inefficacy.

In the D7, a bone marrow biopsy was performed. In the same day, the patient’s blood pressure started to drop, and haemodynamic stability was achieved only with continuous infusion of 22mL/h of norepinephrine.

In the D8, the patient began again to be dyspnoeic and tachypnoeic, and thus was reintubated. Blood tests showed 21,000 platelets/mm³ and 19,000 leukocytes/mm³ with 5% rods. Antibiotics (vancomycin and meropenem) were reinitiated.

In the D9, the patient had a distended abdomen with intraabdominal pressure of 13mmHg; an exploratory laparotomy was performed, and a Meckel diverticulum was resected at 70cm before the ileocecal valve. The surgeons also found hepatosplenomegaly. Blood tests showed 18,000 platelets/mm³, and an arterial blood sample found pH of 7.11, pCO2 of 30mmHg, HCO3- of 9 mEq/L, pO2 of 147mmHg, and lactate of 15mmol/L. Continuous haemodialysis was initiated.

In the D12, the patient needing increasing concentrations of continuous norepinephrine to tolerate haemodialysis and showing no improvement in his general condition, the medical team and the family agreed to define the case as terminal. Haemodialysis and vasoactive drugs were suspended. The patient passed away in the night of D12 to D13, and, upon family agreement, was referred to the Service of Pathology for autopsy.

Slide: Case 19 (Area D)

Four year-old male, presented 12/03 with hepatosplenomegaly and lymphadenopathy, fever and respiratory disturbance. EBV serology was positive and he was diagnosed with mononucleosis. Two months ago he presented with fever and lymphadenopathy involving chest, abdomen and parotid and had hepatosplenomegaly. Positive sorolcgy for CMV and EBV (IgG EBEA-early antigen; 1/2560 and IgA 1/160).

Slide: Case 20 (Area A)


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