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  Table of Contents    
CLINICOPATHOLOGIC CONFERENCE  
Year : 2018  |  Volume : 61  |  Issue : 3  |  Page : 383-388
A 54-year-old male with diabetic nephropathy and suspected disseminated tuberculosis: Clinicopathologic correlation in a rare diagnosis


1 Department of Pathology, Military Hospital, Jalandhar, Punjab, India
2 Department of Medicine, Military Hospital, Jalandhar, Punjab, India

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Date of Web Publication13-Jul-2018
 

   Abstract 


Tuberculosis (TB) and Non-Hodgkins lymphoma (NHL) share similar clinical and radiological features, which make diagnosis a challenge. It is often difficult to rule out a diagnosis of extrapulmonary and/or disseminated TB because of its paucibacillary nature and difficulty in accessing the involved organs. In countries with high prevalence of TB like ours, empirical antitubercular treatment (ATT) is started, and the patient is followed up closely for response. We present a rare case of a 54-year old diabetic male who was suspected to be a case of disseminated TB but had a rapid downhill course despite ATT. A postmortem revealed features of a rare, aggressive T-cell NHL masquerading as disseminated TB.

Keywords: Antitubercular treatment, disseminated tuberculosis, T-cell non-Hodgkins lymphoma

How to cite this article:
Misra P, Jassar A, Ghosh AK. A 54-year-old male with diabetic nephropathy and suspected disseminated tuberculosis: Clinicopathologic correlation in a rare diagnosis. Indian J Pathol Microbiol 2018;61:383-8

How to cite this URL:
Misra P, Jassar A, Ghosh AK. A 54-year-old male with diabetic nephropathy and suspected disseminated tuberculosis: Clinicopathologic correlation in a rare diagnosis. Indian J Pathol Microbiol [serial online] 2018 [cited 2020 May 25];61:383-8. Available from: http://www.ijpmonline.org/text.asp?2018/61/3/383/236626





   Clinical Protocol Top


A 54-year-old male, resident of Ghazipur (UP), presented with 10 days' history of decreased appetite, dyspnea, and decreased urine output. Appetite was reduced, but there was no associated nausea, vomiting, diarrhea, pain abdomen, dysphagia/odynophagia, hematemesis, or hemoptysis. The dyspnea was gradually progressive and associated with easy fatigability, but there was no history of chest pain, palpitations, orthopnea, or paroxysmal nocturnal dyspnea. He complained of decreased urine output but denied any history of dark-colored/smoky urine, hematuria, burning/pain during micturition, or passage of any stone/clots/flesh in urine. There was no history of fever.

He was a known case of diabetes mellitus (DM) type 2 since the last 10 years and had stopped oral hypoglycemic agents on his own about a month back. There was no history of hypertension, heart disease, tuberculosis (TB), or jaundice.


   Clinical Examination and Investigations Top


Clinical examination revealed a middle-aged male with pallor and mild bilateral pedal edema. Pulse was 80/min, regular, and of normal volume while blood pressure was 140/80 mmHg. Systemic examination did not reveal any abnormality. Investigations revealed normocytic normochromic anemia, raised urea, creatinine, hyperglycemia, hypoproteinemia, hypoalbuminemia as well as raised erythrocyte sedimentation rate (ESR), and lactate dehydrogenase [Table 1].
Table 1: Results of lab investigations

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Course in hospital

Over the next 2 weeks, he complained of low backache, generalized weakness, loss of appetite, and (unquantifiable) loss of weight. X-ray LS spine revealed spondylosis, and he was managed conservatively. However, as his pain increased in intensity, a magnetic resonance imaging (MRI) of the dorsolumbar spine was done, which revealed altered signal intensity with heterogeneous enhancement of LV5 and sacrum with presacral and epidural collection (? Pott's spine). ESR was repeated and found to be raised (24 mm fall in 1st h); however, sputum for AFB and Mantoux test were negative, and X-ray chest was normal. In view of the clinical presentation and MRI findings, he was put on antitubercular treatment (ATT) (SHRZ) on day 25 of admission.

However, patient's general condition did not improve despite ATT. On day 28, he was found to have mild hepatomegaly (2 cm below right costal margin) and ?an ill-defined mass in the left iliac fossa. Ultrasound (USG) of the abdomen revealed mild hepatomegaly but no focal lesion or dilatation of intrahepatic biliary channels. Both kidneys appeared normal in size and echogenecity.

Over the next week, patient's condition progressively deteriorated, with loss of appetite and weight. In view of non-improvement despite continued ATT, possibility of malignancy was considered. Tumor markers (PSA and CEA), serum LDH (377 IU/L; range 200–400 IU/L) and upper gastrointestinal (GI) endoscopy were within normal limits. CECT Abdomen done on day 45 showed a pelvic mass lesion in the recto-vesical pouch, pre- and para-rectal region causing asymmetric thickening of the rectal wall mainly on the right side involving B/L seminal vesicles and infiltrating the urinary bladder, the prostate, and the right lateral pelvic wall along with mild splenomegaly, retroperitoneal lymphadenopathy (RPLN), SOL liver, and small left kidney. Sigmoidoscopy revealed evidence of infiltration and a small polyp in the rectum. Multiple biopsies were taken and turned out to be within normal limits on histopathology examination (HPE).

Patient's condition deteriorated further and he now complained of dyspnea and abdominal distention. ECG showed sinus tachycardia. He was tentatively scheduled for laparoscopic RPLN biopsy on the next day, but as his dyspnea increased, he was placed on ventilator and inotropic support. A bedside USG-guided FNAC of RPLN was attempted but failed. Due to increasing azotemia, he had to be started on intraperitoneal dialysis and his general condition improved marginally, though he could not be weaned off the ventilator. On day 60 of admission, he developed bradyarrhythmia and cardiac asystole, from which he could not be revived.

Final diagnosis on death

Sepsis with multiorgan failure? Disseminated TB? Undiagnosed malignancy.

Discussion on clinical protocol by department of medicine

A middle-aged male, known case of DM Type 2 on irregular medication, presented with a short history of dyspnea, easy fatigability, low appetite, and decreased urine output. As the clinical examination did not reveal any specific abnormality other than pallor and bilateral pedal edema and there was no fever, a working diagnosis of uncontrolled diabetes with renal disease was made. The evaluation revealed azotemia, hypoproteinemia, and hypoalbuminemia and no evidence of TB on X-ray chest, sputum, or Mantoux test. However, on suspicion of Pott's spine on MRI spine and in view of his immunocompromised status as a diabetic, he was put on ATT.

Points favoring disseminated TB were generalized malaise, low appetite, history of dyspnea, raised ESR, and imaging findings of a lesion in LV5 along with mild hepatosplenomegaly, RPLN, and an ill-defined pelvic mass. Points against it were the absence of fever, normal chest X-ray, and Mantoux test, and a rapid downhill course despite the ATT.

When his general condition continued to deteriorate despite the ATT and imaging studies revealed an ill-defined pelvic mass with widespread involvement of the rectum, pararectal tissues, bladder wall, retroperitoneal lymph nodes and hepatosplenomegaly, and disseminated malignancy was considered in the differential. However, a specific diagnosis and primary site of the malignancy remained unclear as the common tumor markers were within normal range, serum LDH was marginally raised which can happen in both disseminated TB and low-grade malignancy while multiple endoscopic biopsies were negative for malignancy on HPE.

He was planned for a laparotomy and frozen section biopsy of the mass/RPLN, but unfortunately, his poor general condition precluded this. Although a bedside USG-guided FNAC of the RPLN was attempted, it was unsuccessful, and thus a diagnosis of malignancy could not be proved antemortem.

Final clinical diagnosis

  • Disseminated disease
  • Differential diagnosis of (a) disseminated TB (b) disseminated metastasis from an occult malignancy
  • Terminal event: Sepsis with multiorgan failure
  • Comorbidity: DM type 2.


Pathology protocol by pathologist

Gross findings

At autopsy, body of a middle-aged male, with pallor was seen. The salient finding was a large, firm, nodular para-aortic mass [Figure 1]a, extending from the porta hepatis, and abutting the liver parenchyma [Figure 1]b as well as infiltrating and entrapping left adrenal and left kidney [Figure 1]c, while also encircling the pancreas and part of colon [Figure 1]d and extending onto the posterior abdominal wall, urinary bladder, and rectum [Figure 1]e. Enlarged retroperitoneal lymph nodes were noted and removed [Figure 1]f.
Figure 1: (a) Large, irregular, firm para-aortic mass. (b) Irregular, firm nodules abutting the liver. (c) Irregular mass entrapping the left kidney and adrenal. (d) Mass encircling the pancreas and part of the colon. (e) Gross involvement of the posterior abdominal wall, urinary bladder, and colon. (f) Irregularly enlarged para-aortic nodes with a firm, homogenous cut surface. (g) Cut surface of lung showing congestion. (h) Atherosclerotic plaques in the aortic wall. (i) Left kidney showing distinct corticomedullary junction on cut surface. (j) Enlarged and congested spleen with smooth cut surface (inset)

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In addition, both lungs were voluminous and boggy [Figure 1]g, and there was bilateral pleural effusion. The aorta and left anterior descending branch of the coronary showed atherosclerotic plaques [Figure 1]h. However, there were no cardiac valvular abnormalities, hypertrophy of ventricles, or features of endocarditis. The left and right kidneys were congested and weighed 150 and 180 g, respectively. Their cut surface showed distinct corticalmedullary demarcation, and there was no dilatation or deformation of renal pelvis nor any stones or strictures [Figure 1]i. The spleen weighed 450 g and had a congested cut surface but no nodules [Figure 1]j. The brain weighed 1300 g and appeared grossly normal.

Microscopic findings

Sections from the paraaortic nodes showed complete effacement of the nodal architecture by a monotonous population of intermediate-sized neoplastic lymphoid cells. The reactive cells in the background included small lymphocytes and occasional epithelioid histiocytes, eosinophils, and plasma cells [Figure 2]a. The liver showed nodular parenchymal aggregates and involvement of the portal tracts by the neoplastic cells [Figure 2]b and [Figure 2]c. Sections from the pancreas showed sheets of neoplastic lymphoid cells abutting normal acini [Figure 2]c and those from the aorta showed infiltration of the wall by the same neoplastic cells [Figure 2]d. Sections from the intestine [Figure 2]e and bladder [Figure 2]i show tumor cells infiltrating into the serosa without involvement of the muscle layer or mucosa. Both kidneys revealed numerous sclerosed glomeruli and a dense tumor infiltration in the interstitium [Figure 2]g. Section from the left adrenal showed tumor cells infiltrating the wall and compressing the parenchyma [Figure 2]h. Spleen showed expansion of the white pulp by nodular aggregates of the neoplastic cells [Figure 2]j. Bone marrow biopsy revealed a paratrabecular distribution of neoplastic cells [Figure 3].
Figure 2: Photomicrographs showing (a) Sheets of monotonous intermediate-sized neoplastic lymphoid cells in para-aortic nodes (×100) (b) Nodules of neoplastic cells abutting liver parenchyma (×100) (c) Lymphoma cells expanding portal tracts (×400). (d) Tumor infiltration of the periphery of pancreas (×100) (e) Tumor cells infiltrating the aortic wall (×200). (f) Tumor infiltration of the serosa of the colon (×100) (g) Sclerosed glomeruli (red arrows) with interstitial tumor infiltration (white arrows) (×400. (h) Tumor infiltration of the left adrenal (×200) (i) Tumor cells in the bladder serosa while the mucosa and muscle layer are normal (×100) (j) White pulp expansion of spleen by tumor cells (×100)

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Figure 3: Paratrabecular involvement of bone marrow by neoplastic lymphoid cells (×400)

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On immunohistochemistry, the neoplastic cells from all organs of involvement were positive for leukocyte common antigen [Figure 4]a and [Figure 4]b, negative for CD79b (B-cell marker) [Figure 4]c and positive for CD 45Ro, a T-cell marker [Figure 4]d.
Figure 4: Immunohistochemistry showing (a and b) strong positivity for leukocyte common antigen (×100 and × 400, respectively). (c) Negative reaction with CD79a (×200). (d) Strong positivity of tumor cells with CD45Ro (×200)

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Final diagnosis

Peripheral T-cell Lymphoma (PTCL, nodal type, and Stage IV) of para-aortic nodes involving abdominal organs and bone marrow, in a background of end-stage renal disease with bilateral massive pleural effusion leading to terminal respiratory compromise.

Clinicopathologic correlation

The correlation of the patient's signs/symptoms, altered laboratory parameters, and imaging findings with the disease process are summarized in [Table 2].
Table 2: Clinicopathologic correlation

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Brief comment on peripheral t-cell lymphoma

Non-Hodgkin lymphoma (NHL) affecting mainly extranodal sites, as in this case, can give rise to atypical presentations, thus causing delay in its diagnosis or its misdiagnosis as TB.[1] Some authors have reported a severe form of disseminated TB in whom the atypical course of the disease under treatment led to investigations that unveiled the coexistence a non-Hodgkin lymphoma.[2] TB has been called a great mimicker; but empirical treatment with ATT is justified, especially in a patient with a high index of suspicion for and in countries where TB burden is high.[3]

NHLs are known for their heterogeneous presentation, course, and prognosis. While patients with indolent disease can survive for years even without specific treatment, patients with aggressive disease usually succumb to their illness within months.[4],[5] As compared to B-cell NHLs, T-cell lymphomas are more aggressive and have poorer prognosis.[6] Nodal PTCL, not otherwise specified (NOS) usually involve peripheral lymph nodes but any site may be affected. Their distribution is often generalized, with infiltration of bone marrow, liver, spleen and extranodal tissues; peripheral blood may be involved but leukemic presentation is uncommon and most common extranodal sites of involvement are skin and GI tract.[7]

In the present case, the disease (PTCL, NOS) involved the retroperitoneal (para-aortic) lymph nodes and spilled over widely to involve the liver, spleen, pancreas, bladder, left kidney, left adrenal, rectum, and pararectal tissues. Peripheral blood did not show any lymphoma spill but the marrow had paratrabecular infiltration. Involvement of GIT by PTCL, NOS, is less commonly reported and such presentation of PTCL can masquerade as disseminated TB.[8] Hepatomegaly and jaundice in NHL are fairly common and multifactorial in origin. Direct infiltration of portal tracts is known to occur in indolent lymphomas while aggressive group presents with hepatic mass lesion.[9] In our patient, infiltration of portal tracts was present at the postmortem biopsy.

Renal involvement in lymphomas is fairly common at autopsy but seldom causes overt disease. Most common involvement of the genitourinary system occurs in the form of ureteric obstruction.[10] Other manifestations include glomerulonephritis, renal vein thrombosis, and grossly enlarged kidneys by direct involvement; involvement of testes, bladder, and ovary have also been reported in PTCL, NOS.

PTCL is mostly reported from countries of far east, but Indian studies report a much higher incidence of disease.[11] PTCL is a very aggressive disease with poor response to therapy and has short survival. Treatment regimens usually contain anthracycline-based chemotherapeutic agents or newer agents, but this rarely changes the outcome. Studies have shown that total leukocyte count more than 11,000/cumm, age >60 years, failure to achieve complete remission, and albumin of <3.5 g/dl are associated with a poorer prognosis.[12]

In this case, an unusual aggressive malignancy presented at an advanced stage with nonspecific symptoms and disseminated disease involving multiple organs in an already immunocompromised individual with uncontrolled diabetes and renal disease. As the tumor infiltrated the organs from the serosal side, endoscopic biopsies failed to clinch a histological diagnosis. Serum LDH was only marginally raised, and this has been shown to occur in both disseminated TB and low-grade malignancies.[13] In the absence of any antemortem histological evidence to rule in or exclude TB, he was put on empirical ATT, but succumbed to his disease as the malignancy was aggressive in its course. To conclude, disseminated malignancy and disseminated TB can mimic each other clinically and radiologically and thus cause diagnostic dilemma.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Puvaneswaran B, Shoba B. Misdiagnosis of tuberculosis in patients with lymphoma. S Afr Med J 2012;103:32-3.  Back to cited text no. 1
    
2.
Dres M, Demoule A, Schmidt M, Similowski T. Tuberculosis hiding a non-Hodgkin lymphoma “there may be more to this than meets the eye”. Respir Med Case Rep 2012;7:15-6.  Back to cited text no. 2
    
3.
Uy AB, Garcia AM, Manguba A, Loyola A. Tuberculosis: The great lymphoma pretender. Int J Cancer Res Mol Mech 2016;2:1-4.  Back to cited text no. 3
    
4.
Pileri SA, Ascani S, Sabattini E, Fraternali-Orcioni G, Poggi S, Piccioli M, et al. The pathologist's view point. Part I – Indolent lymphomas. Haematologica 2000;85:1291-307.  Back to cited text no. 4
    
5.
Pileri SA, Ascani S, Sabattini E, Fraternali-Orcioni G, Poggi S, Piccioli M, et al. The pathologist's view point. Part II – Aggressive lymphomas. Haematol Hematol J 2000;85:1308-21.  Back to cited text no. 5
    
6.
Intragumtornchai T, Rotnakkarin P, Sutcharitchan P, Wannagrairoj P. Prognostic significance of the immunophenotype versus the international prognostic index in aggressive non-Hodgkin's lymphoma. Clin Lymphoma 2003;4:52-5.  Back to cited text no. 6
    
7.
López-Guillermo A, Cid J, Salar A, López A, Montalbán C, Castrillo JM, et al. Peripheral T-cell lymphomas: Initial features, natural history, and prognostic factors in a series of 174 patients diagnosed according to the R.E.A.L. classification. Ann Oncol 1998;9:849-55.  Back to cited text no. 7
    
8.
Ranjan P, Dutta S, Kakkar A, Goyal A, Vikram NK, Sharma MC, et al. T-cell lymphoma masquerading as extrapulmonary tuberculosis: Case report and review of literature. J Family Med Prim Care 2015;4:280-3.  Back to cited text no. 8
[PUBMED]  [Full text]  
9.
Risdall R, Hoppe RT, Warnke R. Non-Hodgkin's lymphoma: A study of the evolution of the disease based upon 92 autopsied cases. Cancer 1979;44:529-42.  Back to cited text no. 9
    
10.
Coggins CH. Renal failure in lymphoma. Kidney Int 1980;17:847-55.  Back to cited text no. 10
    
11.
Burad DK, Therese MM, Nair S. Peripheral T-cell lymphoma: Frequency and distribution in a tertiary referral center in South India. Indian J Pathol Microbiol 2012;55:429-32.  Back to cited text no. 11
[PUBMED]  [Full text]  
12.
Vose J, Armitage J, Weisenburger D; International T-Cell Lymphoma Project. International peripheral T-cell and natural killer/T-cell lymphoma study: Pathology findings and clinical outcomes. J Clin Oncol 2008;26:4124-30.  Back to cited text no. 12
    
13.
Steensma DP, Witzig TE. Elevated serum LDH in patients with non-Hodgkin's lymphoma: Not always an ominous sign. Br J Haematol 1999;107:463-4.  Back to cited text no. 13
    

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Correspondence Address:
Aneeta Jassar
Department of Pathology, Military Hospital, Jalandhar - 144 005, Punjab
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJPM.IJPM_728_17

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

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