A 56 year old woman presented with a history of a lump in the breast for 2 weeks. A fine needle aspiration confirmed the diagnosis of breast carcinoma for which she underwent modified radical mastectomy. She has a 3.5cm X 2 cm grade three infiltration duct carcinoma that was ER -ve, PR -ve and HER2 -ve. She had 5 positive axillary nodes with perinodal extension. She was initiated in chemotherapy with FEC (Epirubicin 100mg/mg/m2, Cyclophosphamide 500mg/m2 and 5-Fluorouracil 500mg/m2). She developed tongue pigmentation which increased with each cycle turning the entire tongue bleu-black after four cycles when this picture was taken.
Tag Archives: Oncology Atlas
Hodgkin’s lymphoma has been known for over 175 years. For about 140 of these the malignant nature of the disease was not certain. The hallmark of Hodgkin’s lymphoma is the Reed-Sternberg cell, which was described independently by Dorothy Reed (1902) and Carl Sternberg (1898). Neither considered Hodgkin’s lymphoma malignant. Diagnosis of Hodgkin’s lymphoma is a challenge even today as the case discussed illustrates.
A 21 year old male presented with a swelling of the right side of the neck and fever. Examination revealed cervical lymphadenopathy. No other nodes were enlarged. An FNAC was reported as chronic lymphadenitis. Anti-tuberculous therapy was started. The lymph nodes increased over the next three months and the fever failed to abate. This was attributed to a paradoxical reaction to treatment and the anti-tuberculous therapy was continued. The patient sought a second opinion after four months of therapy. A lymph node biopsy was performed and a diagnosis of Hodgkin’s lymphoma was made. When staged this patient has stage IIIB Hodgkin’s lymphoma.
The common cause of lymphadenopathy are infections – bacterial, viral, mycobacterial or fungal; malignancy – lymphomas or metastatic; and autoimmune diseases. Lymphadenopathy of acute infection resolves spontaneously or following treatment with antibiotics. These nodes are usually inflamed and tender and are rarely confused with malignancy. Persistent lymphadenopathy is commonly due to tuberculosis, malignancy or autoimmune diseases and needs investigation.
Fine needle aspiration cytology (FNAC) is performed by aspirating material, usually using a 21 or 22 gauge needle, and smearing it onto a slide. It has the advantage of being less invasive than a biopsy. The processing time for FNAC is short and reports are often available on the same day. On the flip side only a small part of the lymph node is sampled and the process of smearing disrupts architecture. FNAC is best for diagnosis of malignancies where a diagnosis can be made by examination of single cells e.g. squamous cell carcinoma or an adenocarcinoma. FNAC has limitations in the diagnosis of lymphoma. A negative report does not exclude the diagnosis of lymphoma and all lymphomas can not be classified by FNAC.
Though described by Thomas Hodgkin in 1928, it was only in 1967, when the Reed-Sternberg cell was shown be clonal by cytogenetics, that Hodgkin’s lymphoma was proven to be a malignancy. The two terms prevalent for the disease, Hodgkin’s disease and Hodgkin’s lymphoma reflect the uncertainty about the pathogenesis of Hodgkin’s lymphoma. Hodgkin’s Lymphoma is a lymphoma that almost always arising from the B lymphocytes. What makes Hodgkin’s lymphoma different from other common B cell lymphomas like follicular lymphoma or diffuse large B cell lymphoma?
Most of the cells in non-Hodgkin’s lymphomas like diffuse large B cell lymphoma are malignant. Most of the cells in Hodgkin’s lymphoma are reactive cells – lymphocytes, eosinophils, neutrophils, histiocytes and plasma cells (figure 1). The lymphadenopathy of Hodgkin’s lymphoma is because of normal cells whereas the lymphadenopathy of diffuse B lymphocytic lymphoma or a follicular lymphoma is because of malignant cells. The lymphadenopathy of tuberculosis or any other chronic inflammatory process is due to a reactive infiltrate, much like Hodgkin’s lymphoma. FNAC of a lymph node of a diffuse large B cell lymphoma shows malignant cells making diagnosis possible. FNAC of a node involved by Hodgkin’s lymphoma is most like to give a normal inflammatory infiltrate making it impossible to differentiate between Hodgkin’s lymphoma and a cause of chronic lymphadenopathy like tuberculosis. If a Reed-Sternberg cell is seen on FNAC a diagnosis is possible, but given the paucity of the Reed-Sternberg cell in Hodgkin’s lymphoma this rarely happens. FNAC is appropriate for the initial evaluation of a lymphadenopathy, but a biopsy should to be performed when the results of FNAC are not diagnostic.
|Figure 1. Histology of Hodgkin’s lymphoma. The malignant cell of Hodgkin’s lymphoma is the Reed-Sternberg (RS) cell. The RS cell is surrounded by a reactive infiltrate consisting of T-lymphocytes along with a varying number of eosinophils, neutrophils, histiocytes and plasma cells. A node involved by Hodgkin’s lymphoma has very few RS cells. The bulk of the node is made up by normal cell. (Modified from http://www.flickr.com/photos/euthman/3884125493/)|
Eleven to fifteen percent of the patients with tuberculosis have a paradoxical reaction after starting anti-tuberculous therapy characterized by increasing fever and worsening of clinical and X ray findings (Eur J Clin Microbiol Infect Dis 2003;22:597-602). Paradoxical reaction was first described by Chloremis in 1955 (Am Rev Tuberc 1955;72:527-36) and may be seen 14-270 days after starting anti-tuberculous therapy (Eur J Clin Microbiol Infect Dis 2002;21:803-9). Tuberculoproteins released as a result of rapid killing of bacteria are responsible for paradoxical reaction. Paradoxical reaction in a patient who has been initiated on anti-tuberculous therapy on the basis of diagnosis of tuberculosis made by FNAC, unlike those diagnosed on biopsy, raises the possibility of lymphoma.
Diagnosis of Hodgkin’s lymphoma is not complete without immunophenotyping. This is best done on a biopsy specimen. Given the limitations of FNAC in the diagnosis of lymphoma, it is ideal to perform an excision biopsy of the lymph node if a definitive diagnosis is not possible by FNAC. In case an excision is not possible a large wedge biopsy should be performed. Deep seated lymphomas can be diagnosed by a needle (Tru-Cut) biopsy. The specimen must be sent to a pathologist with experienced and equipment to diagnose lymphoma.
Every oncologist practicing in regions of the world where tuberculosis is prevalent sees patients who have been diagnosed with advanced Hodgkin’s lymphoma after months of anti-tuberculosis therapy. FNAC is an attarctive test in a resource constrained practice but the limitations need to be appreciated. The clinician must understand what the pathologist is trying to say. A report of “chronic lymphadenitis” must not be treated as tuberculosis. The pathologist must not say more than what the FNAC shows. Every “chronic lymphadenitis” is not tuberculosis!
A 62 year old male who had been operated for a carcinoma of the rectum presented with pain and distension of the abdomen. The CT scan showed a fluid with a density more than simple fluid and scalloping of the liver. A diagnosis of pseudomyxoma peritonei was made. There was no evidence of a rectal tumour.
The term pseudomyxoma peritonei was used by Werth to describe a patient with ruptured ovarian cystadenoma and gelatinous intraperitoneal material. It is a term used to describe a clinical picture associated with release of intraperitoneal mucin from malignant and benign tumours. The malignant tumours associated with pseudomyxoma peritonei are low grade tumours, usually of the appendicular ovarian origin. The cells produce mucin but have a very low metastatic potential. This results in a predominant intraperitoneal growth resulting in accumulation of mucin and severe abdominal dissention and symptoms.
The CT scan shows scalloping of the liver and spleen. Scalloping is distortion of the liver/spleen margins because of extrinsic pressure of adjacent peritoneal implants without liver parenchymal metastasis. There is ascitic fluid that is slightly denser than simple fluid density. Occasionally amorphous calcifications may be seen. Primary tumour is usually not visible at diagnosis. Scalloping of the liver and ascitic fluid with a greater than fluid density is seen on this scan.
The outcome of pseudomyxoma peritonei depends of the malignant potential and the origin of the tumour responsible for pseudomyxoma. Appendiceal tumours have the best outcome and gastric tumours have the worst outcome. Tumours which show invasive features have a worse outcome.
The disease is treated by surgical debunking. Intraperitoneal chemotherapy may be given. Hyperthermic intraperitoneal chemotherapy (HIPEC) or early post-operative intraperitoneal chemotherapy (EPIC) may be given. HIPEC is associated with better tolerability, lesser adverse effects and better survival.
Below are images I had taken of a young woman (about 25yrs old). I do not remember what she was admitted for, but if I am not mistaken it was an illness unrelated to Peutz-Jeghers Syndrome (PJD), probably a febrile illness. A colleague of mine asked me if I had seen the circumoral pigmentations of PJD. Fortunately, I had been carrying my Nikon Coolpix 4500 on that day.
PJD is an autosomal dominant disease caused by germline mutations of the gene STK11 (also known as LKB1) located on the short arm of chromosome 19 (19p). It is characterized by mucocutaneous pigmentation, hamartomas of the gastrointestinal tract and a very risk of malignancy. STK11 mutations are not identifiable in about 25% of the patients. These patients are believed to have inactivation of the gene by other mechanisms. About ½ to 1/3rd of the patients have new mutations. The incidence of PJS ranges from 1 in 30,000 to 1:200,000 births
Pigmentation classically involves the lips and buccal mucosa but other areas including hands and feet but may be seen around the nose, orbits anus and genitals. It is caused by melanin. Spots present at birth but may fade with age and adults may not have the spots. About 5% patients do not have pigmentation.
PJS is associated with hamartomatous polyps. Hamartomatous polyps are polyps composed of the normal layers of the intestine but with a markedly distorted architecture. It results from an overgrowth and is not, at least initially, to have a malignant potential. The polyps may be pedunculated or sessile and vary in size from few mm to 3-4 cm. Eighty percent of the patients have jejunal polyps, 40% in the stomach and 40% in the colon. The PJD polyps have no distinctive endoscopic features but can be differentiated from other syndromes by distinctive histopathologic features of arborizing pattern of smooth muscle throughout the polyp. Patients usually present in the second decade of life with abdominal pain, rectal bleeding, anaemia, small intestinal intussusception, bowel obstruction, and rectal prolapse of polyps. Forty to fifty percent of patients need a surgery for polyp related bowel obstruction
From Peutz-Jeghers Syndrome in Familial Cancer Syndromes Editor Douglas L Riegert-Johnson. NCBI 2009
Patients of PJS are at a very high risk of malignancy and the risk is not confined only to the gastrointestinal tract. Almost all patients with PJS will develop a malignancy. PJS increases the risk of small intestinal carcinoma by more than 500 times. The risk of other gastrointestinal cancers, breast cancer, cancer of the uterus and ovary are also increased.
|Cancer||Cumulative Risk*||Relative Risk#|
Data sourced from * Giardiello FM, Trimbath JD. Peutz-Jeghers syndrome and management recommendations. Clin Gastroenterol Hepatol. 2006;4:408-415.
# Giardiello FM, et al Very high risk of cancer in familial Peutz–Jeghers syndrome. Gastroenterology. 2000 Dec;119(6):1447-53
PJD is treated by polypectomy that may be performed by intraoperative endoscopy or double balloon endoscopy. There are no recommendations for screening patients. The disease is rare and evolving formal recommendations will be difficult. Given below is a graphic compilation of screening recommendations from sources listed by Giardiello and Trimbat (see table above).
Internet resources for PJS include