malakoplakia is a rare , chronic , granulomatous inflammatory disease that was first described by michaelis and gutmann in 1902 .
the name " malakoplakia " was derived from the greek " malakos " ( soft ) and " plakos " ( plaque ) in 1903 by von hansemann .
malakoplakia is most commonly found in the urinary tract , but has been reported in the gastrointestinal tract , lung , brain , lymph node , adrenal , tonsil , conjunctiva , skin , bone , abdominal wall , pancreas , retroperitoneum , and female genital tract .
malakoplakia is associated with many coexisitng conditions , such as organ transplantation , tuberculosis , sarcoidosis , allergic conditions , cytotoxic chemotherapy , acquired immunodeficiency syndrome , malignancies , steroid use , alcohol abuse , poorly controlled diabetes , ulcerative colitis , and malnutrition .
, we report a case of malakoplakia in an otherwise healthy 19-year - old female with a review of the literature .
a 19-year - old female was referred to our hospital following the discovery of multiple polyps in the rectum with sigmoidoscopy .
her clinical symptoms were recurrent low abdominal pain and loose stool with blood and foul odor 4 to 5 times a day for 3 months .
when the patient was admitted , she was in relatively good condition with no specific past medical history and did not complain of fever , chill , anorexia , weight loss , or cold sweating . on physical examination , there were no definite abnormal findings except for mild epigastric tenderness and slightly increased bowel sounds .
blood pressure was 110/76 mmhg , pulse rate 106 beats per minute , body temperature 36.3. laboratory tests revealed hemoglobin at 9.0 g / dl , white blood cell ( wbc ) count at 9,050/l with 26.6% neutrophils , 27.2% lymphocytes , 15.2% monocytes , and 0.8% eosinophils .
a peripheral blood smear showed normocytic normochromic anemia , fe of 18 g / dl , total iron binding capacity of 286 g / dl , 0.8% reticulocytes , and stool occult blood over 1,000 ng / ml .
inflammatory markers such as c - reactive protein ( crp ) and erythrocyte sedimentation rate ( esr ) were mildly elevated to 3.03 mg / dl and 42 mm / hr , respectively . urine analysis with microscopic exam showed no abnormality .
stool acid - fast bacillus and tuberculosis polymerase chain reaction were negative , and gram stain showed wbc 10 to 25 and a number of gram - positive cocci and gram - negative bacilli . in the stool culture , salmonella or shigella was not isolated and blood cultures were negative .
serum igg , ige , and hemolytic complement 50 ( ch50 ) complement levels were slightly elevated to 1,800 mg / dl , 236 iu , and 54.2 u / ml , respectively .
colonoscopy revealed very diverse circular or flat elevated mucosal lesions up to 10 cm in size from the cecum to the descending colon , small nodules , mass - like lesions , and erosive small polypoid lesions throughout the colon , particularly in the sigmoid colon ( fig .
after colonoscopy , we initially suspected atypical lymphoma or malignancy . however , lactate dehydrogenase and tumor markers such as carcinoembryonic antigen , ca 125 , ca 19 - 9 , and -fetoprotein were within normal range and an abdominopelvic computed tomography scan revealed no other abnormal findings , except for localized multiple small reactive lymph node enlargements along the mesentery . histological examination of colon lesion biopsies revealed dense histiocyte infiltration with round inclusions of varying sizes in the cytoplasm .
many of these inclusions had round laminated structures with a central dark area and peripheral pale halo .
these structures were stained with periodic acid - schiff ( pas ) , alcian blue , prussian blue , and gomori methenamine silver stains to confirm the presence of michaelis - gutmann bodies with pathognomonic features of malakoplakia ( fig .
these diagnostic tests confirmed the diagnosis of malakoplakia . during antibiotic treatment , diarrhea and abdominal pain improved so she was discharged with instructions to take 500 mg ciprofloxacin twice a day , 25 mg bethanecol three times a day , and 60 mg ascorbic acid once a day by mouth . after the treatment started , the symptoms of abdominal pain and diarrhea disappeared in a week .
after 2 months , crp , esr , and hemoglobin were nearly normal with values of 0.32 mg / dl , 2 mm / hr , and 12.5 g / dl , respectively .
the patient remained on this regimen for 6 months . during the treatment period , no drug side effects were observed .
previous abnormal colonoscopy findings were remarkably improved after 6 months of follow - up , and returned to normal after the end of 12 months ( fig .
the gastrointestinal tract is the second most common site of involvement by malakoplakia , and most of these cases involve the rectum and colon
. clinical manifestation of colonic malakoplakia is very diverse , from asymptomatic to diarrhea , abdominal pain , rectal bleeding , intestinal obstruction , vomiting , malaise , fever , and constipation .
endoscopically , malakoplakia commonly presents in the early stages as soft yellow to tan mucosal plaques or in the late stages as raised , grey to tan lesions in various sizes with peripheral hyperemia and a central depressed area .
malakoplakia can be diagnosed by histology with the presence of the mineralized basophilic structures and michaelis - gutmann bodies .
the etiology and pathogenesis of malakoplakia is still not fully understood , but multiple possible mechanisms have been suggested .
the involvement of microorganisms is supported by reports of patients with malakoplakia who have chronic infections with various organisms such as escherichia coli , proteus , mycobacterium tuberculosis , and staphylococcus aureus .
infections induced by the microorganisms mentioned above are much more common than malakoplakia ; therefore , other factors must contribute .
malakoplakia may also be caused by a defect in lysosomal processing of microorganisms undergoing phagocytosis by macrophages or monocytes .
therefore , incompletely digested microorganisms accumulate in lysosomes and lead to mineralization of calcium and iron salts on residual microorganism glycolipids .
these michaelis - gutmann bodies can be intracellular or extracellular when stained with pas , prussian blue for iron , and von kossa for calcium .
the assembly of microtubules is stimulated by cyclic guanosine monophosphate ( cgmp ) and inhibited by cyclic adenosine monophosphate ( camp ) .
both low cgmp level and reduced -glucuronidase activity have been reported in patients with malakoplakia . in this patient , we initially suspected atypical lymphoma , familial adenomatous polyposis , or other uncommon cancers because of a wide variety of mucosal lesions throughout the colon .
we performed multiple random colonic biopsies to verify the diagnosis and , in all biopsies , michaelis - gutmann bodies characteristic of malakoplakia were observed .
no definite infectious signs were checked , as the patient did not have any specific infectious disease such as pneumonia or otitis media in her childhood .
we could not measure polymorphonuclear leukocyte function through stimulation by cgmp and inhibition by camp .
there may also be a corrlation between immunosuppression or chronic prolonged iellness and malakoplakia because immunodeficient individuals and patients receiving chemotherapy or immmunosuppressive therapy for transplantation constitute a considerable portion of malakoplakia cases .
furthermore , malakoplakia seems to be correlated with malignant neoplasms and systemic diseases , such as systemic lupus erythematosis , mycotic infections , liver diseases , sarcoidosis , ulcerative colitis , cachexia , and drug addiction .
some authors hypothesized that the coincidence of malakoplakia with colonic and rectal adenocarcinoma might begin with local alteration of gut flora and advised physicians to carefully search for a colorectal neoplasm when malakoplakia appears histologically .
however , the patient in this study was not immunocompromised and did not have any suspicious findings of autoimmune disease .
generally , malakoplakia should be differentiated from crohn 's disease , military tuberculosis , sarcoidosis , whipple disease , chediak - higashi syndrome , and malignancies such as colon cancer and lymphoma . to rule out a particularly serious malignant disease and evaluate the response to treatment , follow - up colonoscopies with random biopsies
were performed four times at 3 , 6 , and 12 months , and at 6 months after the end of treatment for a total follow - up period of 18 months .
the first strategy is to increase the intracellular cgmp to camp ratio using cholinergic agonists such as bethanechol and ascorbic acid to improve lysosomal function .
the second therapeutic strategy is to treat the presumed microorganism infection within the colon by antibiotics .
the antibiotics trimethoprim / sulphamethoxazol , rifampicin , and particularly ciprofloxacin have all been used in the treatment of malakoplakia , because these are able to enter macrophages and contribute to intracellular microorganism death .
the duration of treatment is not fixed , but long - term treatment is advised , although its efficacy still remains debated . according to the report ,
an underlying condition is the most crucial factor affecting malakoplakia mortality , and significant morbidity is related to the chronic underlying condition , which can resist local and systemic therapy . in this case
, the patient 's symptoms improved very quickly after antibiotic treatment . since her symptoms and clinical results improved without aggravation after medical treatment
, we speculated that she suffered from malakoplakia without coexisting disease and that immune maturation with aging might play a role .
the etiology of colonic malakoplakia in this patient was unclear since there were no microorganisms in the stool and blood culture .
the patient had no specific past medical history and was not immunodeficient , did not have a malignancy or any chronic illness , and was not in the most frequently affected age group .
in korea , three cases of malakoplakia have been reported [ 8 - 10 ] .
one of these cases was treated surgically , another treated by endoscopic polypectomy , and the last one treated medically .
this is the first case of malakoplakia with very diverse mucosal lesions throughout the entire colon in a healthy young female with no associated disease .
our case illustrates that when very diverse and atypical mucosal lesions are detected on colonoscopy , physicians should consider malakoplakia .
 malakoplakia is a rare granulomatous disease that occurs commonly in the urinary tract and secondarily in the gastrointestinal tract . 
 most reported cases of malakoplakia are associated with immunosuppressive diseases or chronic prolonged illness . here , we report a rare case of malakoplakia in a young healthy adolescent without any underlying disease . a 19-year - old female was referred to our hospital following the discovery of multiple rectal polyps with sigmoidoscopy . 
 she had no specific past medical history but complained of recurrent abdominal pain and diarrhea for 3 months . 
 a colonoscopy revealed diverse mucosal lesions including plaques , polyps , nodules , and mass - like lesions . histological examination revealed a sheet of histiocytes with pathognomonic michaelis - gutmann bodies . 
 we treated the patient with ciprofloxacin , the cholinergic agonist bethanechol , and a multivitamin for 6 months . 
 a follow - up colonoscopy revealed that her condition was resolved with this course of treatment . 
INTRODUCTION
CASE REPORT
DISCUSSION